OMB No. 0925-0001/0002 (Rev. 08/12), Continuation Page Web viewIt is one of the leading biomedical...

Program Director/Principal Investigator (Last, First, Middle): Nelson, Sarah

RESOURCESOVERALL BD2K CENTER: RESOURCES

GENERAL RESEARCH ENVIRONMENT AT UCSFThe University of California, San Francisco (UCSF) is one of the ten campuses of the University of California and is devoted solely to graduate education and research in the health sciences. UCSF is composed of the Schools of Medicine, Dentistry, Pharmacy, and Nursing, and the Graduate Division. It is one of the leading biomedical research and health science education centers in the world. It is also a major health care delivery center in northern California, with a high volume of regional, national, and international patient referrals. It is home to 11 collaborative research institutes, 1,500 laboratories and more than 5,000 ongoing research projects. In 2006, UCSF was one of the first institutions awarded a grant to form an NIH Center for Translational Sciences (CTSI), which is dedicated to research and education in clinical and translational science at UCSF, at affiliated institutions, and in participating communities.

PROFESSIONAL SCHOOLSUCSF’s four professional schools (Dentistry, Medicine, Nursing, and Pharmacy) are ranked in the top tier nationally and internationally (measured by academic quality, publication citations of faculty, and amount of extramural support for research and education) as centers for education and research in the various disciplines. UCSF’s graduate academic PhD programs are also ranked in the top tiers of programs in the biomedical bio-psychosocial disciplines. There are over 35 cross cutting academic departments, 17 multidisciplinary research centers, and many NIH-funded multidisciplinary research grants including 20 Research Program Projects (P01), 9 Center Core Grants (P30), 12 Specialized Center Grants (P50), and 3 Comprehensive Center Grants (P60). The Schools of Medicine (SOM) and Pharmacy (SOP) provide the academic homes for the faculty members at UCSF who are participating in the current proposal. The SOM was established in 1864 and is the oldest continuously operating medical school in the western states. It is ranked as one of the top ten medical schools in the country and operates facilities at seven campuses in San Francisco and Fresno. The SOP was founded in 1872 as the first college of pharmacy established in the west and the tenth in the US. It is ranked as the best Doctor of Pharmacy degree program in the nation by US News and World Report and has been the largest school of pharmacy recipient of NIH research funding every year since 1979. It administers the California Poison Control System, which responds to approximately 600,000 poisoning inquiries each year, saving $30 million annually in medical treatment costs.

GRADUATE DIVISIONThe Graduate Division functions as the administrative and quality control unit for more than 854 PhD students, 593 academic master's students, and 1,100 academic postdoctoral fellows, representing 94 countries. It offers 19 degree programs to students pursuing masters and doctoral degrees in disciplines ranging from bioengineering to chemical biology, from biopharmaceutical sciences and pharmacogenomics to nursing, and from global health to sociology. Graduate programs are organized around several interdisciplinary research areas that often contain members from several departments. UCSF also offers a K-30 supported Advanced Training in Clinical Research certificate program and a Master’s Degree in Clinical Research. The number of postdoctoral scholars appointed at the UCSF campus is larger than the number appointed at any of the other University of California campuses. UCSF has taken national leadership in the establishment of quality standards for the selection, appointment, compensation, and education of postdoctoral scholars. Of UCSF staff, 52.5% are minorities and 68% are women. Of faculty, 27.5% are minorities and 43% are women. Of the student body, 54% are minorities and 64% are women.

RESEARCH INFRASTRUCTUREUCSF continues as one of the leading biomedical research and graduate education centers in the world, and it ranks in the top group of institutions of higher learning in total federal funding for research and training. In the past three decades, UCSF has evolved into a world-renowned biomedical research center with an annual PHS 398 (Rev. 08/12 Approved Through 8/31/2015) OMB No. 0925-0001

Resources Format Page


budget of over $3.3 billion to support its various research, teaching, and patient care activities. A large portion of the extramural funds received is allocated for biomedical research. Research funding primarily is obtained on a competitive basis from the federal government. Additional research funding is received annually from the State of California, the University of California Office of the President, private research foundations, state and local government agencies, private philanthropy, and industry. UCSF was awarded $532.8M in NIH funding in 2011, which was first among public institutions and second among all institutions nationwide. Fourteen UCSF scientific departments ranked among the top 10 in 2011, with five leading their fields in funding: anesthesiology ($8.8 million), internal medicine ($162 million), neurology ($36.4 million), neurosurgery ($16.2 million), and obstetrics and gynecology ($23.3 million). In 2010, the UCSF School of Dentistry received $19.5M, the School of Nursing received $9.9M, and the School of Pharmacy received $22.6M. The School of Medicine ranked first nationally in 2012, with $445.7M in NIH funding. Among faculty members are five Nobel laureates, 36 National Academy of Sciences members, 54 American Academy of Arts and Sciences members, 79 Institute of Medicine members, and 16 Howard Hughes Medical Institute investigators.

RECENT EXPANSIONOver the past decade, UCSF’s capacity for basic science and clinical research in the context of world-class graduate education has been redoubled by the construction of academic facilities at the new UCSF Mission Bay Campus. Currently, UCSF has over 1.5 million assignable square feet (ASF) of research space: ~62,000 ASF in the School of Dentistry, ~1.3 million ASF in the School of Medicine, ~32,000 ASF in the School of Nursing, and ~126,000 ASF in the School of Pharmacy. With the opening of the Neurosciences Building at Mission Bay, another 152,000 ASF of research space became available in the spring of 2012. This total space supports approximately 2,300 Principal Investigators with active sponsored awards. Research and clinical activities take place on the six main San Francisco campuses of UCSF: Parnassus, Mount Zion, Laurel Heights, San Francisco General Hospital, San Francisco Veterans Administration Medical Center, and Mission Bay. A UCSF shuttle bus service (running every 20 minutes) allows for efficient staff, reagent, and mail travel between all main campus facilities.

ACADEMIC DEPARTMENTS OF FACULTY IN THE BD2K CENTER RADIOLOGY AND BIOMEDICAL IMAGINGDrs. Nelson, Barkovich, Hess, Nagarajan, and Xu have appointments in the Department of Radiology and Biomedical Imaging. This is one of the most prominent academic programs in the country with an equal focus on clinical service and translational imaging research activities. The department has consistently been among the top institutions in the NIH rankings and manages a large number of core imaging facilities that provide cutting edge technology to the researcher community at UCSF. These facilities are housed at multiple campus locations and include resources at the Biomedical Imaging Laboratory, the Center for Molecular and Functional Imaging and the Surbeck Laboratory for Advanced Imaging. The department has a strong emphasis on education, with an outstanding residency and clinical fellows program. PhD imaging scientists in the department are active members of the multidisciplinary graduate programs described below, with a particular focus on Bioengineering. The recent formation of a Master’s program in Biomedical Imaging has led to the development of a comprehensive curriculum of hands-on courses in all aspects of imaging science. These will be available to the students and postdoctoral fellows who are participating in Center activities.

NEUROLOGYDrs. Nelson, Barkovich, Gourraud, Henry, Lobach, Miller, Oksenberg, and Rankin hold appointments in the Department of Neurology, the mission of which is to deliver superb patient care, to apply state-of-the-art translational research methods to discover the causes of and treatments for human nervous system disorders, and to educate each generation of medical students, neurology residents and postdoctoral fellows. By fostering cross-disciplinary interactions among scientists around the world, we accelerate the pace of discovery and champion the University's global health initiatives. Current NIH rankings show that the Department of PHS 398 (Rev. 08/12 Approved Through 8/31/2015) OMB No. 0925-0001



Neurology is number one nationally among departments of neurology at US medical schools. This ranking does not take into account the NIH support to our faculty at the San Francisco Veterans Affairs Medical Center, the Gladstone Institute of Neurological Disease, or the Gallo Center. The US News & World Report's Best Hospitals ranking system considers 4,825 hospitals in 14 adult and 9 pediatric specialties. UCSF is currently ranked 6th in the nation overall, with a highest rating (9 out of 9) for patient services. UCSF Medical Center and Children's Hospital are ranked 1st in the San Francisco Bay Area for neurology & neurosurgery services. The Department currently holds 75 funded NIH grants for its 175 faculty members, 91 postdoctoral fellows, 27 clinical fellow, 41 residents, and 202 staff members.

BIOENGINEERING AND THERAPEUTIC SCIENCESDr. Babbitt holds a primary academic appointment in the Department of Bioengineering and Therapeutic Sciences, of which Dr. Nelson is co-Chair. This unique department was formed six years ago and reports jointly to the SOM and SOP. It is the home for 20 primary faculty and has another 43 faculty with secondary appointments. Dr. Nelson was one of the two founding co-Chairs and is now a Vice Chair for Bioengineering Graduate Affairs. Its scientific mission is to perform high-quality basic, translational, and clinical research in the fields of drug development sciences, pharmacogenomics, therapeutic bioengineering, computational biology and systems pharmacology. The faculty are engaged in teaching PharmD and MD professional students, as well as being active in managing and supervising graduate students. There are close interactions with the Department of Bioengineering at UCB, through the joint PhD program and the new joint Masters in Translational Medicine. The faculty have substantial expertise in computational sciences, with a major focus on structural and systems biology.

EPIDEMIOLOGY AND BIOSTATISTICS Drs. Sen and Lobach hold appointments in the Department of Epidemiology and Biostatistics, which is currently located off-campus at 185 Berry Street in the China Basin Landing neighborhood of San Francisco. In 2015, the department will move to a new building that is under construction on the Mission Bay Campus. Its scientific mission is to do outstanding clinical and population-based research, often in collaboration with other departments and institutions, and to guide use of the findings in clinical practice and public health policies. Its educational mission is to train students, fellows and faculty in methods for studying disease etiology and prevention in general populations, for evaluating diagnostic tests and treatment efficacy in clinical settings, and for using evidence-based approaches in clinical practice. The Department currently has 45 salaried primary appointment faculty, 85 affiliated faculty, 135 research and administrative staff, and manages $29 million in direct costs per year, among five divisions (Biostatistics, Cancer Epidemiology, Clinical Epidemiology, Clinical Trials and Multicenter Studies, and Preventive Medicine and Public Health) and other programs and centers (Program in International Health, Global Health Area of Concentration Program, Office of International Programs in the School of Medicine, Biostatistics Research Program Center for Bioinformatics and Molecular Biostatistics, and the San Francisco Coordinating Center).

NEUROLOGICAL SURGERYResearch plays a key role in the UCSF Department of Neurological Surgery, in which Drs. Barkovich and Costello hold appointments. The current research program consists of over 25 principal investigators with a broad variety of research interests reflecting the full range of clinical and surgical activity in the Department. In 2005, the Division of Translational Research was created for the greater facilitation of collaborations between clinicians and scientists. The largest group of investigators comprises the UCSF Brain Tumor Research Center—an organization formed in 1975 and currently funded by over 30 NIH awards, including one of only four Specialized Program of Research Excellence (SPORE) awards for brain tumors from the National Cancer Institute. This group of investigators covers the full range of brain tumor investigation from clinical to basic and is focused on improving the diagnosis and treatment of brain tumors. Investigators with a specialized interest in pediatric brain tumors also reside within this group. Another group of clinicians and scientists comprise the Brain and Spinal Injury Center. This multidisciplinary group of investigators studies brain and spinal cord injury caused by radiation or trauma, and their interests range from the biology of neural injury and PHS 398 (Rev. 08/12 Approved Through 8/31/2015) OMB No. 0925-0001



repair to biomedical informatics and neurological critical care. The third group of scientists is organized around the study of cerebrovascular disease, and focuses on understanding the basis for blood vessel malformations in the brain and on developing better therapies for these abnormalities. A fourth group of investigators is organized around the study of epilepsy and movement disorders. These investigators study the underlying basis for epileptic seizures and have also made significant advances in the use of deep brain stimulation and viral-based therapies for the treatment of Parkinson’s disease. Finally, clinical research for neurospinal disorders is conducted by neurosurgeons specializing in treating degenerative disc disease, spinal tumors, scoliosis, adult spinal deformity, and severe back pain. There is also a neurospinal biomechanics laboratory, which focuses on testing of novel reconstruction methods for tumor resection and deformity correction surgery. The Department of Neurological Surgery currently houses over 20 basic scientists whose work is not only well-funded and nationally recognized, but also is attuned to the clinical implications of the science. In this setting, therefore, translational programs like this one are situated in a highly supportive environment with all of the neurosurgical and neurological skill sets available that would be expected of a neurological gene therapy program.

PSYCHIATRYDr. State is Chair of and Drs. Miller and Sanders hold appointments in the Department of Psychiatry, which is among the nation's foremost resources in the field of child, adolescent and adult mental health. Psychiatry faculty members are recognized for their leadership roles in state-of-the-art, comprehensive and compassionate patient care, pioneering research, excellence in training the next generation of leaders, advancing public policy to advance mental health, and commitment to diversity. Department programs are active at all major UCSF campuses.

RELEVANT CROSSCUTTING RESEARCH INSTITUTES AND CENTERSThese multidisciplinary units are organized around specific themes and have faculty members from multiple departments. They provide substantial resources to the biomedical research community and receive funding from the NIH, NSF, state, private foundations and industrial partnerships, as well as acting as a focus for philanthropy.

CALIFORNIA INSTITUTE FOR QUANTITATIVE BIOSCIENCES (QB3)The QB3 Institute was created by Governor Gray Davis as one of the four California Institutes of Science and Innovation. Spanning UCSF, UC Berkeley and UC Santa Cruz, it promotes basic research in quantitative biosciences and works to ensures that new discoveries are commercialized as quickly as possible. QB3 has grown to include over 220 research groups with 40 members of the National Academies and two Nobel laureates. It has helped to launch 65 companies and has formed three major industry partnerships. The QB3 incubator network began in 2006 and has grown dramatically to include three campus sites and two private partners, with 51 companies currently renting space. Companies in the network have created more than 280 jobs and raised over $230 million in venture financing. The QB3 building at the Mission Bay campus has 96,000 sq. ft. of space on five floors designed to house multi-department and multi-disciplinary laboratories, lecture halls, and shared scientific resources. It also includes the Surbeck Lab for Advanced Imaging, of which Dr. Nelson is the Director. Other critical technology resources are the QB3 Cluster (described below), the Nikon Imaging Center, the Biomedical Micro-and Nanotechnology Fabrication Laboratory, and the Center for Advanced Technology.

INSTITUTE FOR COMPUTATIONAL HEALTH SCIENCESThe UCSF Institute for Computational Health Sciences (ICHS) was created by the Chancellor in 2012 to develop and enhance UCSF’s computational efforts and strategies in basic, translational, clinical and population-based biomedical research. It will be a campus hub for computer scientists and for researchers who employ computation as a primary tool in their biomedical research. ICHS is a critical component of a global

PHS 398 (Rev. 08/12 Approved Through 8/31/2015) OMB No. 0925-0001



UCSF initiative in Precision Medicine, which seeks to aggregate and integrate vast, disparate datasets to advance understanding of biological processes, determine mechanisms of disease, and inform diagnosis and treatment of patients. Beginning with a base of excellent computational faculty dispersed among our four top-ranked professional schools (Dentistry, Medicine, Nursing, and Pharmacy) and Graduate Division, superb research programs and outstanding Medical Center, ICHS will establish a central convening center, hire additional faculty, and build programs for research and education. Establishing training in bioinformatics and working with big data is a priority mission of the ICHS Education subcommittee. Under the leadership of an Executive Committee comprised of a broad set of campus leaders involved in computational research and technology, the ICHS has contributed to the recruitment of several new faculty and is currently interviewing candidates for a permanent Director.

INSTITUTE FOR HUMAN GENETICS (IHG)The Institute for Human Genetics (IHG) is the central hub for human genetics research, education, and practice at UCSF. Initiated in 2006, the Institute has grown considerably over the past 7 years through active recruitment, whereby 29 new faculty members have joined the IHG. The major aim of the IHG is to create an exciting, productive, and collaborative environment for research, training, and clinical application in human genetics. The IHG also provides institutional support and resources, such as the Genomics Core Facilities, which have a large variety of state of the art technology platforms and support services for cost effective, flexible solutions for genomics projects of any size, ranging from full-service, large-scale projects to equipment only support. The UCSF Genomics Core is made up of several satellites located across the UCSF campuses.

The current membership includes 72 active researchers, educators, and practitioners. Most of these individuals use the latest in genomics technology in their research, and quite a few are highly computational in their research. With the advent of high throughput sequencing based methods, such as next generation approaches to whole genome and whole exome sequencing, along with RNA-seq and ChIP-Seq applications, and continuously dropping prices, the demand for access to these technologies by our faculty has dramatically increased over the past several years. As a consequence, the IHG and the EVCP’s office have made several important investments to advance genomics research. Specifically, the IHG has acquired and upgraded two Illumina HiSeq 2500 systems.

MEMORY AND AGING CENTER (MAC)Drs. Lobach, Miller, and Rankin are affiliated with the UCSF in the Department of Neurology. The MAC has over 140 trainees and full-time employees, with faculty that includes fourteen neurologists, five neuropsychologists, a geriatrician, a geriatric psychiatrist, and five advance practice nurses, as well as over 20 clinical research fellows. It was established in 1998 by Dr. Bruce Miller, who was recruited to establish a clinical dementia program within the Department of Neurology. The mission of the UCSF MAC is to provide the highest quality of care for individuals with cognitive problems, to conduct research on causes and cures for degenerative brain diseases, and to educate health professionals, patients and their families. The MAC is multidisciplinary and conducts both clinical and basic science research, in addition to supporting an ever-expanding outpatient faculty practice under the auspices of the Mission Bay Neurology Clinic. Patient care services include neurology, neuropsychology, geriatrics, geropsychiatry, genetic counseling, pharmacy, nursing, social work, and speech pathology that are available to participate in a patient's evaluation. The MAC supports approximately 3,000 clinic appointments per year (1,000 new patient and 2,000 follow-up visits). This large flow of patients, families and caregivers into clinical and research programs includes core projects on Alzheimer’s disease, frontotemporal dementia and healthy aging that each evaluate hundreds of research subjects, with 1,000 individuals participating in over 70 different MAC research projects each year. A team of research assistants and administrators are available to help faculty, fellows and collaborators in implementing projects, including support for patient scheduling. Today, the MAC is housed in the innovative Sandler Neuroscience Center on the Mission Bay campus of UCSF, which brings all the basic and clinical research activities under one roof. The MAC is an international leader in establishing new diagnostic and treatment




approaches to Alzheimer’s disease and non-Alzheimer’s dementias, including frontotemporal dementia, Creutzfeldt-Jakob disease, corticobasal degeneration, and mild cognitive impairment.

HELEN DILLER FAMILY COMPREHENSIVE CANCER CENTER (HDFCCC)The original facility at Mt. Zion is an NCI-designated matrix center, conducting a wide range of inter-disciplinary research in the areas of laboratory, clinical, and population sciences. The HDFCCC integrates activities of more than 250 members working at four major campus and hospital locations (Parnassus, Mt. Zion, SF General Hospital, VA Hospital). The HDFCCC has placed a major emphasis on the integration of programs that include new therapeutic approaches, new ways of detecting cancers and classifying them by molecular markers, population studies that identify risk factors for the disease, and strong basic efforts to increase the understanding of cancer at the molecular level. Dr. Nelson and her collaborators are members of the UCSF Cancer Center and have access to patient populations and resources necessary for collaborative research with the investigators from the Departments of Oncology, Surgery, Neurosurgery, and Pathology housed within the Cancer Center. The HDFCCC also provides support for several core facilities that are used extensively by faculty at UCSF and are available for use by trainees (http://cancer.ucsf.edu/cores/index.php). These include a state-of-the-art Mass Spectroscopy Core, an Array and Genome Analysis Core, a Cell Analysis Core for quantitative PCR and flow cytometry, a Transgenic Mutagenesis core for engineering mutations into the mouse germline, Mouse and Molecular Pathology Cores for analysis of mouse and human tissues, a Pre-Clinical Core for carrying out preclinical oncology trials, and a Clinical Research Support Services Core that assists with protocol development, data management, regulatory compliance, contract development, and patient registration for clinical trials. Bioinformatics support is provided by the Biostatistics and Computational Biology Core as well as by the Translational Informatics Group in the HDFCCC. HDFCCC resources and core facilities will be available to the investigators of the BD2K Center.

CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE (CTSI)The UCSF CTSI was established in 2006 as one of the first 12 academic institutions selected to be part of the NIH's national clinical & translational science consortium. The CTSI mission is to create a comprehensive, integrated academic home that promotes research and education in clinical and translational science at UCSF, affiliated institutions, and in participating communities. Its goals are to (1) support, enhance, and integrate existing training programs, increasing the number of trainees from diverse disciplines and improving the quality of their training in clinical and translational research methods; (2) support, improve, and integrate existing infrastructure to enhance the design and implementation of clinical and translational studies, fostering collaborations to achieve a diverse spectrum of high quality, original research; (3) enhance career development of clinical and translational researchers by providing mentoring and opportunities to catalyze original research and by changing the academic culture to appropriately reward multidisciplinary collaborative work; and (4) create a "virtual home" providing contemporary communications to simplify collaboration, to provide an optimal informatics matrix for conducting innovative research, and to nurture the growth of clinical and translational science. The CTSI has established 13 interrelated programs that provide training, services, and opportunities needed. These programs are led by senior scientists drawn from diverse disciplines in each of UCSF's four health science schools—Dentistry, Medicine, Nursing, and Pharmacy. The CTSI is beginning a second cycle of 5-year NIH funding (UL RR024131).

MULTIPLE SCLEROSIS CENTER (MSC)The MSC has established outstanding clinical and research units that provide a resource-rich environment for basic, clinical, epidemiological and translational research. It has an active postgraduate fellowship program and numerous nationally and internationally known MS researchers, many of whom have an impressive record of mentorship and collaboration. It has been awarded numerous national and international recognitions for MS clinicians and patient-oriented researchers, many of whom have an impressive record of mentorship and collaboration, including the Chairman of the department of Neurology Stephen L Hauser (Chair of the Department of Neurology and Director of the MSC); Emmanuelle Waubant (pediatric MS); Scott Zamvil (neuroimmunology); Christian Von Büdingen (humoral immunology); Jorge Oksenberg (genetics); Sergio PHS 398 (Rev. 08/12 Approved Through 8/31/2015) OMB No. 0925-0001



Baranzini (gene expression); Pierre-Antoine Gourraud (genetics and bioinformatics; Sam Pleasure (neurobiology and differentiation); Jonah Chan (oligodendrocyte biology); and Katerina Akassoglou (axon immunobiology).

OTHER UCSF RESOURCESLIBRARYThe UCSF Library and Center for Knowledge Management is one of the preeminent health sciences libraries in the world, containing an extensive and exceptionally rich collection of monographic and periodical literature in the health sciences, with substantial holdings in the biological and physical sciences, the social sciences, psychiatry, and psychology. This collection contains over 844,214 volumes, 57,440 electronic full-text serials and 13,068 electronic health sciences serials. The library incorporates state of the art library computer systems, such as MyAccess that replaces the card catalog with a streamlined computer search system. The library also houses The Center for Instructional Technology, which offers a wide range of documentation and training on using the Collaborative Learning Environment (CLE). The CLE provides a versatile framework designed to meet the current and future needs for learner-centered environments, collaborative learning, and other collaborative activities at UCSF. Library materials not available on the San Francisco campus may be requested through other University of California campuses. Special collections contain both secondary and primary source material from the earliest medical history to contemporary projects in AIDS, tobacco control, biotechnology, and managed care. Historical materials are concentrated in the history of the health sciences, California medicine, anesthesia, Osleriana, medical artifacts, and East Asian medicine. All faculty and students have access to print and electronic resources regardless of UCSF departmental or programmatic affiliation.

Digital LibraryGALEN is the Digital Library at UCSF. PubMed@UCSF is publicly available, but access to full text articles is limited to computers on the UCSF network or to approved offsite computers. It provides access to the MEDLINE database as well as other NLM databases, and is strong in clinical and basic sciences, nursing, dentistry, and health care planning and administration from 1966 to the present. References published between 1958 and 1965 can be viewed through OLDMEDLINE. The MELVYL Catalog is used to locate books at all UC libraries, and California Periodicals to find journals/titles at other University of California, California State University, and California libraries. Many other important databases are available, including Current Contents, BIOSIS, and PsycINFO.

Center for Knowledge ManagementThe Center for Knowledge Management is an innovative division of the library. Its multidisciplinary staff develops knowledge bases and on-line tools for the health sciences, pursues applied research projects related to UCSF informatics problems, serves as a laboratory for graduate students who are interested in using new technologies to solve important health sciences information problems, and supports the library's sophisticated computing and communications infrastructure.

Interactive Learning CentersThe Interactive Learning Centers maintain student-computing facilities in the library and in the Medical Sciences Building, with PC and Macintosh computers, printers, software, documentation, consulting support, and connections to the Internet. Electronic classrooms are available at both locations for reservation by UCSF faculty members. The Multimedia Development Lab (MDL) provides hardware, software, and consulting support for development of curriculum-integrated, educational materials. Video digitizing, flat art scanning and slide scanning are among the capabilities available in the MDL. Education and Consulting Services offers curriculum-integrated instruction and scheduled seminars that assist students and faculty in the use of information management tools such as databases, the Internet, and personal file management software. Librarians consult with faculty and students topics of high interest.PHS 398 (Rev. 08/12 Approved Through 8/31/2015) OMB No. 0925-0001



RELEVANT GRADUATE PROGRAMSBIOENGINEERINGThe close proximity of UCSF and UCB has fostered numerous collaborations among faculty members on the two campuses with regard to developing quantitative approaches to addressing fundamental problems in biological and clinical sciences. In the early 1980s, scientists who were heavily involved in these interactions on the two campuses proposed the formation of the UCSF/UCB Joint Graduate Group in Bioengineering (JGGB). This fully integrated educational program was approved in 1983 and is authorized to offer Ph.D. degrees that are conferred jointly by the Graduate Divisions of both campuses. Over the past twenty-three years, the JGGB has become one of the pre-eminent educational programs in the country and is well known for the diversity and excellence of the training it provides. Its objective is to teach doctoral students to bring the methods of modern engineering to bear on problems in biology and medicine, and to learn how to teach others to do the same. This combination of expertise is very much in demand in academia and in industry, and provides a wide range of employment opportunities to graduates of the JGGB. Of particular interest to students is the multi-disciplinary environment that is provided by the two campuses, which means that the breadth and depth of the training offered to students is of an order larger than a single department could provide. Faculty in the JGGB come from more than twenty departments in the professional schools at UCSF, six departments from the College of Engineering at UCB and several non-engineering departments. Hence, there is a wide array of research opportunities and state-of-the art facilities available to the students.

BIOLOGICAL AND MEDICAL INFORMATICS PROGRAM (BMI)The development of the current BMI Program began in 1997 and led to the creation of tracks in basic biology and medical sciences. The focus for faculty in BTS will be the Biological Informatics (BI) component, which has its own training grant and recruitment process. There are 23 faculty members in this track from six departments whose mission is to train students from quantitative backgrounds in computer science, mathematics and statistics, whose interests are aimed at performing research at the interface of biology, computation and informatics. There are currently 29 students in the program, with expected incoming classes of 6-10 students per year. To enhance the range of training opportunities that are available to their students, the BI group has formed an alliance with faculty focused on Biophysics and Systems Biology to develop a core curriculum for training students in quantitative biology. The recent HHMI/NIBIB Interfaces Grant Program that was designed to sponsor graduate training programs in interdisciplinary research has funded curriculum development. This includes boot camps in biology, mathematics and computation, as well as team challenges that teach students to rely upon interdisciplinary collaboration to solve complex biological questions. Electives in algorithm design, objective oriented programming, statistical methods in bioinformatics and scientific software development ensure that the students get exposure to quantitative analysis methodology. A new Bioinformatics track in Quantitative Genetics/Genomics is under development in collaboration with the Institute for Human Genetics, and is expected to attract students with interests in statistical and population genetics and related areas. New courses under development, along with core courses in iPQB, will form the core curriculum.

BIOMEDICAL SCIENCES GRADUATE PROGRAM (BMS)The UCSF BMS Program is an interdisciplinary graduate research program that seeks to equip students with the training and research tools to study the function of tissue and organ systems in development, physiology, and disease. The Program is based on training students for higher levels of biological systems integration by the incorporation of two features that were not part of traditional department-based graduate instruction in fields such as physiology, experimental pathology, and anatomy. First, students in the program must acquire a level of competence in molecular biology, biochemistry, and cell biology comparable to that expected of students in traditional biochemistry and molecular biology programs. Second, the study of key developmental, physiological, and pathological features of human biology is also incorporated into the curriculum. This new




approach to training will result in a new generation of inter-disciplinary biomedical scientists who are able to forge collaborations that break down traditional research boundaries.

EPIDEMIOLOGY & TRANSLATIONAL SCIENCEThe PhD program in Epidemiology and Translational Science is a new degree track in the Department of Epidemiology and Biostatistics (DEB) at the UCSF School of Medicine, offered in collaboration with UCSF's renowned Clinical and Translational Sciences Institute. Doctoral students receive high caliber training in core skills of epidemiologic and biostatistical methods along with opportunities for practical experience to enhance classroom training.

MASTER OF TRANSLATIONAL MEDICINE (MTM)This multidisciplinary program focuses on technology and teaches the critical-thinking skills needed to navigate the challenges inherent in translating research from the laboratory bench to patient bedside. The course work, which is designed to complement this diversity, gives students the opportunity to address real-world problems, such as the critical need for expediting new therapies to treat devastating diseases, and it is anticipated that some of this work will lead to innovations with commercial potential. The master’s program spans an intensive 12-month curriculum with coursework that includes fundamentals of bioengineering, physiology, disease processes, core medical principles, clinical research methods, clinical trials design, and key concepts in business and management. The program culminates in a capstone design-project experience in which students work in interdisciplinary teams co-advised by an engineering faculty member and an MD, PharmD, or clinician. Projects cover various phases of the translational process, and often have the potential to continue beyond the scope of the master’s program.

MASTERS OF SCIENCE IN BIOMEDICAL IMAGING (MBI)This new MS program in Biomedical Imaging enrolled its first entering class in the fall of 2011. The program is intended for advanced pre-doctoral students, postdoctoral fellows, medical residents, and faculty members who wish to utilize imaging sciences to broaden their investigative projects. Coursework includes instruction in core theory drawn from imaging physics, engineering, and mathematics, linked to physiology and disease processes. Hands-on laboratory courses are an important part of the curriculum with experiments relevant for characterizing pathologies, monitoring response to therapy, and assessing underlying disease processes. Specialized topics such as quantitative imaging, research design, image analysis, and technology assessment will be available through electives.

NEUROSCIENCE GRADUATE PROGRAMUCSF offers an interdisciplinary program for graduate training in neuroscience. The purpose of this program is to train doctoral students for independent research and teaching in neuroscience. The UCSF Neuroscience program seeks to train students who will be expert in one particular approach to neuroscientific research and in its related basic science disciplines, but who will have a strong background in other areas of neuroscience as well. Almost all important areas of modern neurobiology are represented at UCSF.

PHARMACEUTICAL SCIENCES & PHARMACOGENOMICS (PSPG)The graduate program leading to a PhD in PSPG is multidisciplinary. It has a dual focus on Pharmaceutical Sciences, which includes the scope of disciplines from chemistry to biology and from pharmacology to bioinformatics that are involved in the discovery and development of medications, and Pharmacogenomics, which covers the application of genetics and genomics to drug action and disposition. The 51 faculty members in the program come from both the School of Pharmacy and the School of Medicine. There are currently 51 graduate students in the program; of those who have selected research advisors, 24 are mentored in SOP laboratories and 19 are mentored in SOM laboratories. The program is based at Mission Bay but there are a significant number of faculty and students at Parnassus and at other UCSF locations. The PSPG program is partially funded by a NIH training grant. The graduates are highly sought after and upon completion of their




thesis, 39% of the graduates go into academic positions or postdoctoral fellowships, 44% go into industry; the remainder goes into other health related occupations.

TRAINING IN CLINICAL RESEARCH (TICR)The TICR Program, supported by an NIH K30 Award, is considered one of the most successful efforts of its kind in the nation. Although the emphasis of these programs has been on clinical research training primarily for fellows and junior faculty, enhancing and extending the TICR program to focus more strongly on translational research is a centerpiece of the recently funded UCSF Clinical and Translational Science Institute (CTSI), which is part of the NIH Roadmap Initiative. TICR related coursework is an option for trainees with more clinically driven research projects, and the Responsible Conduct of Research course in the TICR program is required for all trainees in this T32 program.

SPECIFIC FACILITIES AND RESOURCESLABORATORYSurbeck Laboratory for Advanced Imaging The Surbeck Lab, directed by Dr. Nelson, is in the California Institute for Quantitative Biomedical Research (QB3), The Institute involves more than 100 scientists housed in a building on the UCSF Mission Bay campus that is part of a public/private biomedical research park, in a new building at UC Berkeley and in two new facilities at UC Santa Cruz. The QB3 building at Mission Bay has roughly 96,000 sq. ft. of space on five floors designed to house multi-department and multi-disciplinary laboratories, lecture halls, and shared scientific resources. The Surbeck Laboratory of Advanced Imaging houses state-of-the-art human 3T and 7T MR scanners. The space dedicated to MRS/MRI research under the principal investigator’s direction is in the California Institute for Quantitative Biomedical Research (QB3) on UCSF’s Mission Bay campus. It occupies approximately 750 sq. ft., with an additional 186 sq. ft. of part-shared space dedicated to tissue culture, and includes bench space for 10 investigators. This dedicated area will be used for cell culture, biological assays, cell extraction, and other activities. The electronic lab space includes over 400 sq. ft. of floor space with utility sink, counters, and storage cabinets. The manufacturing lab space includes 500 sq. ft. of floor space with utility sink, counter and storage cabinets

Center for Molecular and Functional ImagingThe Center for Molecular and Functional Imaging (CMFI) includes approximately 61,000 sq. ft. of laboratory and office space for faculty, post-doctoral fellows, graduate students and staff. It is located at the China Basin Landing building, which is close to the Mission Bay campus. Additional space on the first floor of the building contains clinical outpatient imaging capabilities. This space includes an impressive array of research laboratories and clinical imaging equipment. Key facilities include whole body MR scanners, PET/CT systems, a cyclotron, radiochemistry and physics laboratories. The pre-clinical imaging suite includes a microPET/CT (Inveon, Seimens, Germany); microSPECT/CT (X-SPECT, GammaMedica, CA); a bioluminescence and fluorescence imaging station (IVIS 50, Caliper Life Sciences, CA) and an optical tomographic system (FMT, VisEn Medical, MA). This suite also housed an automatic gamma counter and phosphor imaging system (Wizard 3, Perkin-Elmer, CT), a small and whole-body cryrogenic sectioning instrument (Cryocut 1800, Reichert-Jung, Germany) and appropriate shielding, dose calibrator and a 4 ft. hood for handling radioactive materials. All imaging scanners are fully equipped with oxygen supplies, anesthesia systems and proper evacuation of excess isoflurane out of the imaging suite. Digital autoradiography, radioisotope well-counters, and a cryogenic microtome are available, as well as a large animal surgical suite with dedicated digital angiography and fluoroscopy system, a contrast injector, autoclave, and anesthesia capabilities for small and large animals.




Biomedical and Biochemical NMR LaboratoryIn the adjacent building to QB3 is the NMR Laboratory, which includes a 500 MHz NMR scanner, used for HR-MAS tissue studies, a wide bore 600 mHz system, and an 800 MHz and 2 600 MHz NMR systems used for in vitro and molecular structure determinations. The 500 and wide bore 600 MHz NMR spectrometers are integrated with a HyperSense™ (Oxford Instruments) DNP polarizer. Both of these magnets are used to run biomedical samples and they have complimentary features, including high-resolution magic angle spinning (HR-MAS) spectroscopy capabilities, and micro-imaging capabilities allowing for NMR studies of biopsy and surgical tissues, cell and tissue cultures, and murine models of cancer. The 800Mhz and narrow bore 600MHz scanners are available for chemical analysis, structure determination or running cell bioreactor studies.

Biomolecular Resource and Mass Spectrometry FacilityThis facility supports DNA sequencing, oligonucleotide and peptide synthesis, protein micro sequencing, and a full array of modern mass spectrometric technologies. The Cell Culture Facility is a Core for preparation of media, and a source for major biochemical and molecular biological reagents. Commonly used cell lines are maintained. The University library carries all major biological journals, and an extensive collection of books. Electronic subscriptions to major journals are provided for all campus sites. Core imaging facilities include access to confocal microscopy, live cell imaging, whole animal imaging, and digital capture electron microscopy, HPLC, FPLC, and standard chromatographic equipment for protein and nucleic acid purification is available, together with appropriate equipment for preparative and analytical ultracentrifugation, spectroscopic analyses, and scintillation counting. Extensive hood space and necessary equipment is available for synthesis, purification, and characterization of organic and inorganic small molecules. A staffed and equipped microchemical facility provides services requiring amino acid analysis, protein sequencing, peptide synthesis, oligonucleotide synthesis, DNA sequencing, and reagent purification. In addition, many individual labs are equipped for PCR, oligo synthesis and DNA sequencing. State-of-the-art facilities for printing, scanning, and analysis of DNA microarrays are available. A robotics center is available for small molecule design and screening is available on the 5th floor of Byers Hall.

Biomagnetic Imaging Laboratory The Biomagnetic Imaging Laboratory is a 1,000-sq. ft. space located in the Department of Radiology and Biomedical Imaging at UCSF. The Center houses several faculty members and includes a Magnetoencephalographic imaging lab (MEGI), TMS-Mapping Laboratory (TMS) and the Speech Neuroscience Laboratory (SNL). The BIL currently houses a whole head 275 channel MEG system (Omega 275, VSM Medtech, Inc. Port Coquitlam, BC Canada). This system has 275 axial gradiometer MEG sensors distributed over the whole cortex, with 29 reference channels used for noise cancellation. EOG/EMG, ADC/DAC, triggers and 128 channels of simultaneous EEG. All channels may be used simultaneously and are managed by a common hardware interface, signal-processing unit and acquisition workstation computer. The system comes with CTF's advanced processing and analysis software. The new and current MEG system has a sensor density (2.2 cm), with whole head coverage. The OMEGA 275 has FDA 510K clearance for scanning of the brain. Although VSM Medtech has discontinued manufacturing new MEG machines, MEG Services International has agreed to continue to maintain the UCSF machine under an existing maintenance contract. The center also houses a state-of-the-art Nexstim 4.0 Non-invasive transcranial magnetic stimulation (TMS) system with MRI-based stereotaxic navigation and simultaneous electromyography (EMG) and integrated video/audio recording. Nexstim supports both single pulse and rTMS bursts using air-cooled figure-of-eight TMS coils.

The Helen Diller Cancer Research Building This opened in the summer of 2009, and consists of 89,000 sq. ft. of research space. The construction was initiated by a major contribution from a private donor. When fully occupied, the building will house 46 laboratories and more than 400 scientists. It consolidates research programs in basic cancer research, brain tumors, and urologic oncology, as well as population and behavioral sciences research including epidemiology,




cancer screening, chemo-prevention and health policy. Although some of the Cancer Center core facilities will remain at the Parnassus and Mount Zion campuses, the new building has facilitated rapid access to critical instrumentation and to several of the key collaborators participating in this proposal. The immediate impact of the opening of the new building has been the opportunity for seminar series that focuses on cancer imaging research and can readily draw on the participation of the Mission Bay research audience. The investigators in this proposal will take advantage of this remarkable array of new resources and will contribute by providing critical infrastructure for cancer researchers to make use of the imaging equipment, as well as stimulating the development of new collaborative research grants. Facilities include the brain tumor tissue bank, as well as equipment and staff to support genome analysis (DNA sequencing, SNP, and quantitative real-time PCR), cell analysis (flow and image cytometry), informatics, mouse pathology, tissue histology, and microarray construction and analysis.

The Sandler Neurosciences Center This is a 237,000-sq. ft. five-story building containing academic offices, wet laboratories, a clinical research unit, a neuroimaging suite, multi-species vivarium, numerous meeting rooms and an auditorium, all dedicated entirely to neuroscience research. The building brings together the UCSF programs for Neurology (chair, Stephen Hauser, MD), the Institute for Neurodegenerative Disease (IND; director, Stanley Prusiner, MD) and the Center for Integrated Neuroscience, for a total of over 100 principal investigators who use a variety of techniques ranging from molecular biology to systems neuroscience to clinical research. The design of the building and inclusion of a broad range of investigators are meant to promote cross-disciplinary collaboration.

State LaboratoryThe State lab includes wet (bench work) and dry (computational work) space in Rock Hall at UCSF Mission Bay Campus. At present the laboratory is in the process of moving from Yale to UCSF, The State lab is fully equipped for computational, molecular biological and molecular genetics research. For bioinformatics support It has access to the IHG and QB3 clusters. For sample management, it has automated pipetting and bar code scanning resources, as well as prior experience with similar large scale sample analysis.

CLINICALImaging The Department of Radiology and Biomedical Imaging has extensive clinical facilities that include 150 faculty, 40,000 sq. ft. of space and over 120,000 annual examinations. There are 8 1.5T and 10 3T whole body MR scanners in facilities at Parnassus Heights, Mount Zion, China Basin, Sam Francisco General Hospital and the VA Medical Center campuses. All systems are kept state-of-the-art to meet the department’s goal of rapid translational MR research. Techniques and protocols developed on research scanners can be installed on the clinical scanners and applied in clinical practice. This has occurred in many cases including spectroscopic imaging, echo-planar imaging, high-resolution imaging, image post-processing (reception profile corrections, serial alignments, multimodality registration), and diffusion and perfusion fMRI (both acquisition and analysis). The x-ray facilities as well as a Hologic Bone Densitometry unit occupy 11,000 sq. ft. of clinical space in the Ambulatory Care Center. The Nuclear Medicine Program at the Moffitt-Long Hospital has two ADAC Forte SPECT systems, one ADAC Vertex SPECT systems, a GE Discovery VH with x-ray CT and coincidence imaging capabilities, and a Siemens Exact HR+ PET System, associated computers for image reconstruction, display, analysis, and interpretation, and an in vitro laboratory with well-counter and radiopharmacy. The cyclotron and outpatient PET/CT scanners are located in space adjacent to the CMFI at the China Basin facility.

Memory and Aging Center (MAC)The MAC has fourteen neurologists, five neuropsychologists, a geriatrician, a geriatric psychiatrist, and five advance practice nurses. It is a multidisciplinary unit and conducts both clinical and basic science research, in addition to an ever-expanding outpatient faculty practice under the auspices Medical Center Mission Bay




Neurology Clinic. The UCSF MAC Clinic is directed by Dr. Bruce Miller and includes specialists from a wide variety of disciplines. Patient care services include neurology, neuropsychology, geriatrics, geropsychiatry, genetic counseling, pharmacy, nursing, social work, and speech pathology that are available to participate in a patient's evaluation. There is a large flow of patients, families and caregivers into clinical and research programs including core projects on Alzheimer’s disease, frontotemporal dementia and healthy aging that each evaluate hundreds of research subjects over the course of a year. A team of research assistants and administrators are available to help faculty, fellows and collaborators in implementing projects, including support for patient scheduling.

Multiple Sclerosis Center (MSC)The clinical activities of the MSC take place in a comprehensive adult and pediatric specialty outpatient clinic that is currently housed within a newly renovated suite in a building adjacent to the MBC campus, (about 1000 ft. from the laboratories). The MSC serves the population of Northern California and is also a primary reference resource for patients across the US and the world. The clinic is staffed by fifteen neurologists, all of whom are specialists in the care of patients with MS, and is supported by superb nursing and ancillary staff, including one full-time nurse clinician, two licensed vocational nurses, one social worker, one full-time neuropsychologist, and two full-time receptionists. A significant effort is dedicated to patient’s education and support groups. Approximately 1,000 new patients are seen each year and approximately 4,500 visits are completed for clinical follow-up and clinical research projects, including 8 clinical trials. Research laboratories are located in the recently inaugurated Sandler Neurosciences Center in the UCSF Mission Bay Campus. The five-story, 237,000 square foot building is the seventh research building constructed at the MBC and one of the largest integrated university neuroscience research and clinical-care centers in the country.

Langley PorterThe LPPH&C is located at 401 Parnassus Avenue, and is part of the Parnassus campus of UCSF. LPPH&C consists of an adult inpatient unit (22 licensed beds), an adult Partial Hospitalization Program (daily census ranges from 12-17) and adult/child outpatient services (approximately 20,200 visits per year). Primary diagnoses for patients in all services include major depression, anxiety and psychosis. LPPH&C serves all ethnic and socio-economic groups who reside in San Francisco and the greater Bay Area, as well as those referred from areas throughout the Western United States. Departmental administrative and computer support offices are available at this site, and it is the hub for a shuttle service that links the main campus and other sites, including SFGH and SF-VAMC.

Benioff Children’s HospitalThe UCSF Benioff Children's Hospital is recognized throughout the world as a leader in health care, known for innovation, technology and compassionate care. For more than a century, it has offered the highest quality medical treatment. It is one of the top children's hospitals in the nation, according to a ranking by US News & World Report. Clinical expertise covers virtually all pediatric conditions, including cancer, heart disease, neurological disorders, organ transplants and orthopedics as well as the care of critically ill newborns. At the current time the 180 bed Benioff Children's Hospital is a "hospital within a hospital" with more than 150 specialists in almost 50 specialties. There are programs designed specifically for young patients, such as a 50-bed Neonatal Intensive Care Nursery, recreational therapy for recovering kids and 60 outreach clinics throughout Northern California. Doctors at UCSF were the first in the world to successfully perform surgery on a baby still in the womb. They also developed life-saving treatments for premature infants whose lungs aren't fully developed. Hospital services that are customized for young patients include:

Child Life to help children and their families adjust to hospitalization and make their stay as positive as possible

Compass Care, comprehensive palliative care for children with chronic life-threatening conditions as well as those who need end-of-life care




Social workers, who are trained in the needs of children and their families

In the area of neurology and neurosurgery, the Benioff Children’s Hospital is one of the leading hospitals in the nation. It has the largest brain tumor treatment program in the nation and ts the only comprehensive epilepsy center in Northern California. It is also one of the nation's largest centers for kidney and liver transplants. The AIDS program is the most comprehensive in the nation and the surgical eye care program is the largest in Northern California. In the area of orthopedics, the hospital is internationally recognized for treating the spine, including deformities, degenerative disc disease, tumors and fractures.

ANIMALAlthough there is no animal experimentation planned as part of this proposal, there are numerous facilities available to the investigators in the eventuality that this changes. The animal research and care program at UCSF is accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care International and receives periodic inspection by the Animal and Plant Health Inspection Service of the US Department of Agriculture.

COMPUTERIHG ClusterThe Institute for Human Genetics recently invested $800,000 in a new HPC cluster installed at the UCSF Data Facility located at Minnesota Street, near the Mission Bay campus, which is dedicated to high-throughput sequence analysis. In support, the university established a high-speed (10Gbit) link between the Genomics Core Facility at the Parnassus Campus, which maintains several Illumina HiSeq 2500 and other DNA sequencers, and the IHG computing cluster at Minnesota Street to facilitate rapid data transfer and analysis. This pipeline was created to support a variety of high throughput next generation sequencing projects. This system currently has 52/864 nodes/CPUs and 52TB of fast storage and 300 TB of archival storage to support the genomic applications. Specifically, the cluster consists of: 48 Dell R620 nodes, each with 16 cores and 128 GB of RAM; 2 R820 nodes, each with 32 cores and 1 TB of RAM. In total 800 cores are available for computations. Each node has a 1 GB, 10 GB and FDR inifiniband connection. The 1 GB is used for node-to-node communication, the 10 GB is for NFS data stores while the FDR is used for MPIO and connection to our GPFS data store. The GPFS store is a DDN SFA-12k with 60 TB of high-performance storage. Our NFS store acts as a tier 3 storage for data at rest and home folders, this is powered by a internally built cluster and currently has 300 TB of capacity. All controls are redundant and the ingress and egress point from the cluster is over a dedicated 10 GB link.

QB3 ClusterAt the University of California, San Francisco (UCSF), we currently maintain a HPC cluster UCSF maintains a HPC cluster to support the research of a range of quantitative/computational investigators, which is associated with the QB3 and is located in Byers Hall at the Mission Bay campus. This Linux-based shared cluster has been in operation since 2005, and is periodically upgraded with additional nodes; the last major upgrade was 2 years ago when 1152 cores were added to the system. The cluster operates on a co-op basis, whereby individual investigators provide funds for the addition of new hardware, maintenance, and system administration; the access to the cluster is then proportional to the amount of funds invested. The cluster currently has 4,678 cores of a variety of types (most are dual-processor 4- or 6-core Xeon64 machines, each with at least 2 GB RAM per core and a 120 GB hard disk), primarily backed by 36 TB of fast network array storage housed in a total of 19 racks. The cluster supports approximately 30 research groups, primarily in the areas of structural biology, systems biology and biomedical imaging.

Neuroscience ClusterTo support KBase at UCSF, the UCSF Neuroscience Private Cloud Cluster is a dedicated, scientifically agile, computational cluster located in the Sandler Neurosciences Center (SNC) secure server room facility. The cluster provides on-demand, self-service, secure access to virtualized computational workstations and cluster PHS 398 (Rev. 08/12 Approved Through 8/31/2015) OMB No. 0925-0001



job scheduling nodes to neuroscience and neurology related faculty and their collaborators. The virtualized environment allows investigators to “right-size” their computational resources to the datasets and analytics in use by seamlessly running a set of computational cores, ram, and storage using pre-defined templates of operating systems, job schedulers, and analytic software. The cluster is maintained by professional system administrators with expertise in the OpenStack platform and experience with scientific software configuration, monitoring and tuning. Administrators also assist investigator and their staff with configuring the pre-defined analytic templates. The cluster is designed to scale-out easily with the addition of cluster nodes (current node specification is dual Xeon 8 core/16 Thread processors, 384 GB RAM, 9 TB usable clustered storage. The storage architecture (Ceph) provides automatic redundant copies of all data blocks protecting against data loss upon drive failures. The cluster operations were piloted between April and August 2013 and in September 2013 “went live” with 112 cores/224 threads of execution, 2.7 TB RAM, 63 TB usable cluster storage. Investigators may use the cluster on a recharge basis for resources used or may purchase dedicated nodes to expand the capacity of the cluster. There is no theoretical limit to the size of the cluster and the practical limit given available space and power in the SNC server room is a cluster of >1,000 cores. Additional data storage is available in the SNC facility and in the UCSF Data Center services on a recharge basis for long term storage and offsite backup of raw and analyzed datasets.

Memory and Aging Center General Computing EnvironmentIn addition to its specialized high performance cluster, the MAC maintains a general computing infrastructure comprised of 125+ Dell Windows XP/7 desktop and laptop personal computers, 15+ Apple Laptops/Desktops, 6 Dell Linux workstations, 3 Dell file servers with combined storage capacity of >7.0 TB providing file and print services and an Apple OS X intranet/sftp server. The computing infrastructure is regularly replaced (3-4 year replacement cycle), and all equipment is covered under active warranty/service contracts. All laptops, desktops, and servers are protected by current antivirus and firewall software and are backed up at least nightly. Backups are encrypted and rotated off site at least monthly. The MAC employs a full-time system administrator, and most members of the MAC Technology Team are able to serve a backup system administrators/desktop support. Networking and centralized services such as email are provided and maintained by the UCSF Information Technology Department.

Picture Archiving and Communication System (PACS)The Department of Radiology and Biomedical Imaging archives imaging from all clinical digital modalities in PACS. Images are available on approximately 100 dedicated display stations throughout the University at the Parnassus Heights, Mt. Zion, China Basin Landing, San Francisco General Hospital, and the San Francisco Veterans Administration Medical Center campuses. In addition to dedicated PACS workstations, images can be viewed from any computer with a web browser without the need of specialized hardware or software. Studies from the last ten years are kept online, and can be viewed on the diagnostic systems within minutes of request, without relying on reading from slower optical or tape media. The PACS core systems contain over 50 terabytes of RAID storage. All of the core servers and most of the display stations are connected via gigabit Ethernet built on a redundant Cisco Catalyst 6500 core. Remote sites throughout the UCSF metropolitan area network are connected by gigabit fiber, or SONET ring, with the latter scheduled to be phased out over the next two years. The PACS team includes eight staff with expertise in network engineering, programming, system administration, quality assurance and administration.

Radiology Research Computing Services (RRCS)The Department of Radiology and Biomedical Imaging has a Research Computer group that provides infrastructure for networking and systems administration. Over 130 LINUX workstations are supported. All of the computer workstations and servers have software tools for performing research data management. The major research facilities have high-speed land/wireless data network, automatic tape back-up and archival, CD, DVD, optical disk juke boxes. Access to clinical imaging data is possible via the high speed network, but is restricted based upon HIPAA regulations. The research scanners each have an image archive that can be reached from the clinical scanners in order to deposit data for further analysis. In addition to systems and PHS 398 (Rev. 08/12 Approved Through 8/31/2015) OMB No. 0925-0001



network support, the Research Computer group provides support for access to the QB3 cluster a number of specialized software packages. These include image anonymization, DICOM transfer, image reading and writing tools with a number of different common input and output formats, the IDL and MATLAB packages, spectral quantification packages including LCModel, jMRUI, AMARES and QUEST, and more general public domain software tools such as VTK, ITK, FSL, and FAST for image registration, segmentation and visualization.

Quantitative Image Processing Center ( QUIPC) This is a unit in the Department of Radiology and Biomedical Imaging that brings image processing technologies, data management and services for clinical and research purposes. This includes reformats, registration, segmentation, ROI analysis, image post-processing for parametric data (fMRI, DTI, T1, T2, T1rho), and novel algorithm development. For clinical applications, it provides state-of-the-art quantitative image processing capabilities using FDA approved software, including co-registration, segmentation, ROI analysis, and RECIST measurements. Post-processing can also be pipelined for cohort or long-term studies to ensure consistent and efficient. A staff of programmers and trained clinical imaging technologist are available to help with research data workflow development and management. Other services include development of web-based report-forms, data analysis and statistics, multi-center data management, security and curation. QUIPC also supports a research PACS to augment clinical and pre-clinical imaging data management. This system allow for multi-center studies in a secure fashion, with backup and archival services provided by the Radiology Research Computing Service (RRCS).

State Laboratory Bioinformatics ResourcesThe lab has 6 Mac Pros, Intel Xeon 64-bit systems with 8-16 CPUS, 8-18 GB of SDRAM, 2-6 TB of RAID HDD. These have dual-boot ability for Windows and Mac operating systems allowing the use of tools written in either environment. There is 1 Dell Precision T7400 with 8 CPUs, 20 GB SDRAM and 6 TB of RAID HDD. Specialized, custom designed software are available for automated processing of the large volumes of data generated by high-throughput sequencing and genotyping microarrays. Alongside pre-installed open source and proprietary software we have written and implemented the following tools:

SEQer : This is a pipeline for processing and analyzing high-throughput sequencing data in a Unix-based high-performance cluster environment. It makes use of parallelization to rapidly and efficiently process unaligned sequence to annotated single nucleotide variant (SNV) and insertion/deltion (indel) predictions using BWA for alignment and SAMtools for variant prediction. In addition it can predict de novo SNVs in family-based data. This supports multiple target files (e.g. exome capture, targeted capture) and multiple reference genomes (e.g. hg18, hg19, mm9, ds3).

Targeted sequencing: SEQer has been modified to manage pooled data to allow analysis of Molecular inversion probes (MIPs), capture arrays, or Raindance targeted sequencing. Once the target is defined the pipeline can run automatically on all forms of targetted sequencing.

Indel detection: To accurately predict de novo insertion/deltion (indels) we have designed a specific indel analysis pipeline. The aligned and sorted BAM files produced as an intermediary in SEQer (above) are passed into Dindel. Putative indels are identified then local realignment is used to refine the call. By peroforming local realignment for indels in all family members and accurate assessment of de novo status is made.

Annotation: Cross referencing predicted variants with other sources of data (e.g., genes, conservation scores, brain-expression, frequency data) is key to downstream analysis. To allow accurate and fast annotation of region-based and single nucleotide data we have designed customisable annotators that use multi-level indexing and binary search algorithms for rapid processing.

CNVision (www.cnvision.org): This is a pipeline for processing and analyzing genotyping data to predict copy number variation (CNV). The pipeline can run on all major operating systems (Windows, Mac OS, Linux) and PHS 398 (Rev. 08/12 Approved Through 8/31/2015) OMB No. 0925-0001



uses parallelization for rapid and efficient throughput. It uses three CNV prediction tools to maximise accruacy: PennCNV, QuantiSNP and GNOSIS (in-built) and assigns expected positive predictive values based on the overlap and previous confirmation data.

Primer prediction: To allow simple and consistent confirmation of predicted variants we have written an automated pipeline to retrieve reference sequence around a variant, generate primers using Primer3, testing with in-silico PCR and cross referencing against dbSNPv135; in addition a Sequencher input file is generated for simple analysis of Sanger sequencing results.

OFFICEThe investigators participating in the BD2K Center have office space adjacent to their laboratories within the appropriate buildings at Mission Bay, China Basin and Parnassus. Programmers, students and postdoctoral fellows will be assigned cubicles or shared office space in the relevant faculty laboratories The Project Manager will be located in administrative space in the suite where the Director Dr. Nelson has her office and the Educational Coordinator will occupy administrative space in the suite where Dr. Babbitt is located.

OTHEREnvironmental Health and Safety The UCSF Environmental Health and Safety Office monitors the use of radiation, chemicals, biohazards, and provides training and education programs for researchers and employees. All radioactive use is conducted under UCSF Broad-License for Radioisotope Use.

ShuttlesFree shuttles are available between the multiple sites associated with each of the institutions. At UCSF this includes Parnassus Avenue, Mission Bay, Laurel Heights, China Basin Landing, Mount Zion Hospital and Cancer Center, the Veteran’s Affairs Medical Center, and the San Francisco General Hospital.

Student servicesHealth care for students is located at their home campus, and Post-doctoral fellows have healthcare and benefits coverage as part of their appointment at UCSF. Additional in-house resources that would be available to students include: access to personal computers, workstations, and central mainframe facilities, the UCSF Student Computer Center, central mainframes on each campus, and free time on supercomputers that are tied into the network through a UC system-wide consortium. Campuses are also connected to each other by a high-speed data link, internet and video conferencing capabilities are available.

OTHER MAJOR EQUIPMENTThere are many major pieces of equipment available for the proposed study discussed in the sections above. Additional information about UCSF Core Facilities can be found at http://cores.ucsf.edu/.




SUBCONTRACT RESOURCES: LBNLGENERAL RESEARCH ENVIRONMENT AT LBNLLawrence Berkeley National Laboratory (LBNL) is a member of the national laboratory system supported by the US Department of Energy (DOE) through its Office of Science. It is managed by the University of California (UC) and is charged with conducting unclassified research across a wide range of scientific disciplines. Located on a 200-acre site in the hills above the UC Berkeley campus that offers spectacular views of the San Francisco Bay, Berkeley Lab employs approximately 4,200 scientists, engineers, support staff and students. Its budget for 2011 is $735 million, with an additional $101 million in funding from the American Recovery and Reinvestment Act, for a total of $836 million. A recent study estimates the Laboratory’s overall economic impact through direct, indirect and induced spending on the nine counties that make up the San Francisco Bay Area to be nearly $700 million annually. The Lab was also responsible for creating 5,600 jobs locally and 12,000 nationally. The overall economic impact on the national economy is estimated at $1.6 billion a year. Technologies developed at Berkeley Lab have generated billions of dollars in revenues, and thousands of jobs. Savings as a result of Berkeley Lab developments in lighting and windows, and other energy-efficient technologies, have also been in the billions of dollars.

Thirteen Nobel prizes are associated with Berkeley Lab. Fifty-seven Lab scientists are members of the National Academy of Sciences (NAS), one of the highest honors for a scientist in the United States. Thirteen of our scientists have won the National Medal of Science, our nation's highest award for lifetime achievement in fields of scientific research. Eighteen of our engineers have been elected to the National Academy of Engineering, and three of our scientists have been elected into the Institute of Medicine. In addition, Berkeley Lab has trained thousands of university science and engineering students who are advancing technological innovations across the nation and around the world.

RESOURCES FOR THE BD2K CENTER DIVISION OF COMPUTATIONAL SCIENCESVisualization GroupDrs. Ushizima, Weber, and Morozov hold research scientist career-track position appointments in the Computational Research Division, particularly in the Visualization Group. The Visualization Group's mission is to assist researchers in achieving their scientific knowledge discovery goals through visualization and analysis, while simultaneously advancing the state of the art through research. Their objective is to develop new capabilities in high performance visualization, analysis, and related data-intensive technologies. The development of these capabilities is driven by the needs of contemporary computational and experimental science projects central to the mission of the DOE Office of Science. The Visualization Group’s collaborators are diverse, ranging from theoretical astrophysicists to computational and experimental bioscientists. All have a theme in common: the need to understand complex systems through visual inspection of simulation results. Their portfolio includes projects in basic and applied research, advanced software development, and deployment to the scientific community. Highlight of their diverse research and development projects aare located on the Visualization Group's Vignettes pages. These range from algorithmic development in visualization and analysis, to applying these techniques and technologies to solve specific science knowledge discovery problems. Examples of activities from the Visualization portfolio are as follows:Algorithm development and optimization of performance for modern, extreme-scale architectures. One objective is to study how fundamental algorithmic architecture and designs can make effective use of modern computational architectures, through techniques like hybrid parallelism. Recent results show promise for scaling fundamental visualization methods like volume rendering and streamline calculation to very high levels of concurrency, a requirement for transitioning into the exascale regime. Related, their studies have shown that up to a 30x performance gain is possible on some codes and platforms depending upon settings for tunable algorithmic parameters, algorithmic optimizations, and use of device-specific features.PHS 398 (Rev. 08/12 Approved Through 8/31/2015) OMB No. 0925-0001



Visualization and analysis software tool development and deployment. Another group objective is to impact science by enabling scientific knowledge discovery through the use of visualization and analysis software tools. Their portfolio includes productization of many of their research ideas, and we have a long history of doing just that through individual software tools (see the Visualization Group's software page), as well as taking a leadership role in large, multi-institution efforts that serve large computational and experimental science communities like the SciDAC-2 Visualization and Analytics Center for Enabling Technologies (VACET), which brought production-quality, petascale visualization and analysis capabilities and tools to DOE's supercomputer centers, the SciDAC-3 Scalable Data Management, Analysis, and Visualization Institute (SDAV), which continues this mission through 2017, and the Advanced Simulation Capabilities for Environmental Management (ASCEM) effort, which is developing and deploying an integrated approach for efficiently and cost-effectively minimizing environmental, safety, and health risks associated with the movement and impact of underground contaminants. Many of these efforts involve deployment in VisIt, the large-scale visualization and analysis tool, and their team is active developers of this project.Extreme-scale climate data analysis. We are designing, developing, and deploying next-generation tools, which are distributed to the world-wide climate science community, for analyzing and visualizing massive climate data sets to aid in the understanding of how their climate is changing. Carbon sequestration. We have designed, developed, and deployed leading-edge computer vision, image processing, and analysis technology to aid science researchers in understanding how to best store carbon dioxide in porous media.End-to-end data management, analysis, and visualization of extreme-scale simulation data. Contemporary plasma physics simulations have recently entered the regime of simulating trillions of particles, which produce an extremely large amount of data: a trillion particles of output, or 30 terabytes of data per-timestep. The team has developed new methods and tools to enable the capture, storage, analysis, and visualization of such data, and demonstrated these methods on modern DOE supercomputing platforms..

DIVISION OF PHYSICAL BIOSCIENCESBiology in the 21st century is becoming a quantitative and predictive science. We are now poised to return to the origins of scientific inquiry—natural philosophy—as the tools and concepts of physical science become applicable to the central concerns of biology. The mission of the Physical Biosciences Division, in which Dr. Arkin is a Faculty Scientist and the Division Director, is to provide the multidisciplinary intellectual backdrop and the physical resources to build the programs and tools that will make this vision a reality. Building on the extraordinary advances in temporal and spatial resolution and breakthroughs in modern computational and theoretical science, the Division's goal is to catalyze the development of biology as a quantitative, predictive science.

SPECIFIC FACILITIES AND RESOURCESLABORATORYArkin LaboratoryThe Arkin group has 5,963 sq. ft. of mixed laboratory and office space localized in one building; housed in the Energy Biosciences Building in the Dept. of Bioengineering 5th floor and 4th floor Energy Biosciences Institute spaces. In addition, the Arkin Lab has two wet benches and two desk spaces at the Joint Bioenergy Institute and twenty-two computational stations at their KBase site in Emeryville. Additional facilities for imaging and biological analysis are available at the Lawrence Berkeley National Laboratory through the Physical Biosciences Division, where Dr. Arkin is a Faculty Scientist and the Division Director. The group also has access to laboratory and university imaging, flow cytometry facilities and a micro fabrication lab.

The site has 20 wet benches within 8 rooms dedicated to wetlab use, and access to full molecular biological facilities. This includes all the accoutrements of a modern molecular biology lab, including high-end PHS 398 (Rev. 08/12 Approved Through 8/31/2015) OMB No. 0925-0001



microscopes (Deltavision deconvolution scope and epifluorescence microscopes), multiple fluorescence plate readers, flow cytometers, a new Sony cell sorter, Illumina MiSEQ sequencer, liquid handling robots, warm rooms, incubators, shakers, hood, anaerobic chambers, dark room, cold rooms, pH meters, nanodrop spectrometers, multi-purpose centrifuges, oven, water baths, centrifuges, speedvac, PCR Tetrad Thermal Cyclers, MilliQ Biocell, SV5 Stereomicroscope, spectrophotometer, desiccation cabinet, balances, electroporator, electrophoresis and gel visualization systems, -80oC Thermo freezers, -20oC freezers, 4oC refrigerator, deli-style 4oC refrigerator, biosafety hood, dual syringe pump, fluorImeters, etc.

CLINICALNot applicable.

ANIMALNot applicable.

COMPUTER KBase Group and Arkin LabAs lead laboratory for the DOE Systems Biology Knowledgebase flagship software (KBase), Dr. Arkin’s group maintains a 20,000 core cloud-enabled infrastructure that has 3 petabytes of storage spread among four national laboratories. KBase central has access to 12,000 cores for data processing via both open-stack and cluster interfaces and runs on the 100 Gbit/s ESNET2 network, as well as a host of smaller clusters, servers, and workstations. Additional computer resources within the Arkin laboratory include 33 desktop workstations, 3 mid-end linux fileservers for small project usage, 5 terabyte file server for large-scale project usage, 1 forty node cluster for comparative genomics and functional genomic analysis, modern software. Researchers in his group also have access to the National Energy Research Supercomputer Centers technical support and supercomputer farm including top-end Cray T3E`s and IBM SP2s.

National Energy Research Scientific Computing Center (NERSC)LBNL has access to leading-edge computing platforms and services through the NERSC as well as several departmental clusters. NERSC has recently installed a Cray XC30 system that will form the heart of NERSC's computational capability. Known as Edison, the XC30 features124,800 compute cores for running scientific applications, 332 terabytes of memory, and 6.4 petabytes of online disk storage with a peak I/O bandwidth of 144 gigabytes (GB) per second. Once fully deployed, Edison will have a theoretical peak performance of 2.39 petaflops/second. NERSC also operates a 153,408-core Cray XE6 (Hopper) which contains 6392 nodes with two 12-core AMD processors per node, interconnected by a high-speed torus network to achieve a peak performance of 1.29 petaflops, making it one of the most powerful supercomputers in the world. Each node has either 32 or 64 gigabytes of memory, and the system has 2 petabytes of disk space. Another system, known as Carver, is an IBM iDataplex system with a total of 7680 Intel Nehalem processors. These clusters are fully instrumented for detailed measurement of communication and power consumption and can be used for trace capture of full-scale HPC applications. NERSC's research in data-intensive computing is grounded in their operation of a major production facility, the PDSF (Parallel Distributed Systems Facility).

All NERSC systems are connected to the NERSC Global Filesystem (NGF), a collection of centerwide file systems, based on IBM’s GPFS, available on nearly all systems at the facility. The several different file systems comprising NGF, including one providing a common login user environment for all our systems, one for sharing data among collaborators on a science project or team, and one for high bandwidth short term storage across systems at the facility. The main focus of NGF is data sharing, ease of workflow management (i.e., not moving data around or maintaining unnecessary copies of data), and data analysis. These systems are connected to a High Performance Storage System (HPSS) for archival storage. NERSC's HPSS system currently contains more than 42 petabytes, making it one of the largest unclassified archival storage systems in the world.




Other architectural test-beds at LBNL that are available to the project and can be accessed through LBNL include:Jesup: This is a 160 node testbed cluster, used to explore emerging hardware and software technologies. Some of the areas of exploration include Hadoop/MapReduce, Flash Storage, Virtualization, NoSQL technologies, and scalable databases. The node configuration is identical to the Carver nodes, quad-core Intel Xeon X5550 ("Nehalem") 2.67 GHz processors (eight cores/node) with 24 GB of memory per node.Dirac: This is a 48-node Fermi GPU cluster consisting of QDR InfiniBand-connected Nehalem host-nodes to act as a testbed for GPU computing that are integrated with the Carver cluster. The GPU accelerated nodes consist of 44 nodes containing NVIDIA C2050 “Fermi” GPUs, and 8 containing NVIDIA C1040 “Tesla” GPUs. Recently added are 2 multi-GPU nodes: 1 node containing 4 Fermi GPUs, and 1 node containing 4 Tesla GPUs. The system includes a complete set of development tools for hybrid computing, including CUDA, OpenCL, and PGI GPGPU-targeted compilersAccess to the LBNL facilities from anywhere in the US or the world is available through ESnet, which provides a 100-gigabit Ethernet backbone connection between NERSC, LBNL and other DOE national laboratories. ESnet also provides major backbone links including peering with domestic and international research and education networks.

OFFICEOffice space for students and researchers working on the KBase aspects of the Knowledge Network are provided in the Arkin laboratory. There are interactive spaces on every floor of the Energy Biosciences Building, including quiet areas for reading and writing, informal meeting space, a kitchenette and dining area, and balcony space. Designed for interactions, the building common spaces are shared with 9 hotel desks and 2 open offices. A central facility for autoclaving and dishwashing is provided on the lower floor. There is also access is to the core analytical facility, which has numerous analytical chemistry platforms.

OTHER MAJOR EQUIPMENTAt LBNL there are the following: DeltaVision Deconvolution Microscope, Qiagen QiExtractor robot, Partec Flow Cytometer with Robbywell 96 well plate autoloader, Tetrad PCR Engines, Axon Microarray Scanner, Biomek FX liquid handling robot, Biomek 3000 liquid handling robot, fermentation system, Affymetrix Fluidics Station, Agilent Bioanalyzer, NPE Quanta Analyzer, Zeiss epifluorescence microscope, Tecan and Beckman Coulter microplate readers, and an Electrolab bioreactor.



Date post:	26-Mar-2018
Category:	Documents
Upload:	vannga
View:	213 times
Download:	1 times

OMB No. 0925-0001/0002 (Rev. 08/12), Continuation Page Web viewIt is one of the leading biomedical...

Documents