A Medical Research Organization
“People, not Projects”
Transforming discoveries
High risk, high reward research
Few constraints
Generous and flexible funding
Howard Hughes Medical Institute
Howard Hughes Medical Institute $10.6 billion invested in
research and science education since 1985
- $9 billion for research and research support
- $1.6 billion for science education, international research
Endowment of $16 billion* *close of FY 2011
Scientific Leadership Robert Tjian, Ph.D. President, HHMI and Professor of Biochemistry & Molecular Biology University of California-Berkeley Jack Dixon, Ph.D. Vice President and Chief Scientific Officer Science Department, HHMI and Professor of Pharmacology, Cellular & Molecular Medicine, and Chemistry & Biochemistry University of California, San Diego
Gerry Rubin, Ph.D. Vice President and Director, Janelia Farm Research Campus Sean Carroll, Ph.D. Vice President for Scientific Education and Professor of Molecular Biology and Genetics University of Wisconsin, Madison
Medical Advisory Board: A Committee Guiding Scientific Review and Policy
David Baltimore, Ph.D. Nobel laureate President Emeritus and Robert Andrews Millikan Professor of Biology California Institute of Technology J. Michael Bishop, M.D. Nobel laureate Director, G.W. Hooper Foundation and University Professor University of California, San Francisco Michael Botchan, Ph.D. Richard and Rhoda Goldman Distinguished Professor of Biochemistry and Co-Chair of the Department of Molecular and Cell Biology University of California, Berkeley Gerry Fink, Ph.D. Herman and Margaret Sokol Professor Whitehead Institute for Biomedical Research Massachusetts Institute of Technology Carol Greider, Ph.D. Nobel laureate Daniel Nathans Professor & Director Molecular Biology & Genetics Johns Hopkins University School of Medicine Rowena Matthews, Ph.D. G. Robert Greenberg Professor Emeritus of Biological Chemistry and Research Professor Emeritus, Life Sciences Institute University of Michigan
Elizabeth Nabel, M.D. President Brigham and Women's/Faulkner Hospitals, Boston Janet Rossant, Ph.D., F.R.S. University Professor of Molecular Genetics and of Obstetrics and Gynecology, University of Toronto Chief of Research The Hospital for Sick Children, Toronto Phil Sharp, Ph.D. Nobel laureate Institute Professor, Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology Bruce Stillman, Ph.D., F.R.S. President, Cold Spring Harbor Laboratory Marc Tessier-Lavigne, Ph.D. President, The Rockefeller University Craig Thompson, M.D. President, Memorial Sloan-Kettering Cancer Center
HHMI’s Major Programs
HHMI Investigators
Janelia Farm Research Campus
International Research
Science Education
The Science Program at HHMI Seeks
To nurture exceptional scientists at
all career stages
To create a framework for discovery
To connect basic biology and
medicine
The HHMI Science Department
Oversees the flagship Investigator Program 1. 75 host institutions
2. 344 Investigators and 50 Early Career Scientists
3. Conducts investigator reviews for renewal decisions
3. Selects new investigators with open competitions
Oversees the international projects/scholars program
1. K-RITH studying HIV/TB in South Africa
2. International Scholars modeled after the Early Career Scientists program
Oversees Collaborative Innovator Awards program 1. Currently, eight (8) research teams funded
Science Department budget: ~$650M/year Average of $1.4M USD/investigator 344 Investigators 50 Early Career Scientists
HHMI Investigator Program
The HHMI Investigator Life Cycle
Infant
Student
M.D.
Ph.D.
Postdoctoral Training
Faculty Scientist
Publications Recognition
Tenure University Scientific
Leadership
HHMI Review @ 5 Years
Successful Review
Unsuccessful Review
Industry
Chair
Dean
HHMI Investigator
HHMI Investigator Competition
High Risk Research
National Academy (147)
Nobel Prize (13)
Strategies to maximize an investigator’s impact
1. “People, not projects”: Promote freedom to focus on projects driven by passion, incentive to emphasize creativity and a sense of responsibility to harness resources to study risky but high impact questions
2. Minimize non-research requirements
3. Require 75% of time to be spent on “active conduct of research”
4. Provide extensive administrative, legal, operational and scientific assistance, both at Headquarters and at the host institutions
5. Provide salary and benefits for investigators and other lab personnel
6. Enable investigator to manage generous operating budget for personnel and research expenses
7. Enable applications for major equipment purchases during four rounds of capital funding annually
8. Foster critical review and scientific collaborations through annual scientific meetings and workshops
•High Risk Research •Creative, Innovative •Productive, High-Impact •Scientific Meetings •Web Page Updates •Faculty Responsibilities
•Criteria •Review Materials •Research Presentation •Advisors: MAB, SRB, ad hoc •HHMI Final Decision
•Salary •Fringe Benefits •Operating Budget ($600K -
$1.2 million) •Occupancy Payments to
Host Institution
•Success - 5 years support •Non Success - 2 years
support •Rate 80%
Outcome Support
Expectations 5 Year Review
A Model That Fosters Innovation and Invention
2,477 inventions
1,270 active licenses
1,242 patents
976 pending patent applications
100+ start up companies
Measures of Success
HHMI: A Powerful Model
72 Host Institutions
158 Members of the National Academy of Sciences
12 Lasker Award winners
13 Nobel laureates
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HHMI Investigator Competitions History
Year Type Selected
1994 General (all levels) 41
1997 General (all levels) 70
2000 Computational Biology (all levels) 12
2000 General (0-7 years experience) 36
2002 Patient Oriented (6-16 years) 12
2005 General (4-10 years) 43
2007 Patient Oriented (4-16 years) 15
2008 General (4-10 years) 55
2009 Early Career (2-6 years) 50
2011 Plant (all levels >4 years) 15
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When the opportunity arises to influence a field or a career stage, HHMI undertakes a
special emphasis competition
Structural biology (~1980’s)
Computational biology (2000)
Physician-scientists in patient-oriented research (2002, 2007)
Hughes Collaborative Innovator Awards (2008 and 2012)
Early career scientists (2008)
Plant Biology (2011), in collaboration with the Gordon and
Betty Moore Foundation
Current Investigator Competition
We invite applications from more than 200 institutions (universities and medical schools, research institutes and independent hospitals)
Individuals apply directly via online system Streamlined applications: CV, Research Description (e.g. 3000
words), Future Plans (e.g. 250 words), self-evaluation of most significant work
Multiple rounds of peer review are used to select new Investigators
This includes experts in the field, Medical Advisory Board (MAB) and Scientific Review Board (SRB) members. In addition, a selected number of HHMI Investigators participate in the early review stage.
Does Our Review Process Retain Only the Best People?
Reviewing the HHMI Investigator
“The most important single task that Jack Dixon and I have at HHMI is to review the reviewers.”
Robert Tjian, President of HHMI
Scientific Review
The Review Process
Reviews take place every 5 years; no review for ECS (a six year appointment)
All reviewer panel votes are counted for each investigator
No progress reports are required between formal reviews
The Reviewers are:
A mixture of experts in a specific field and “knowledgeable generalists”
Especially important to include skilled evaluators of scientific talent
Members of the Scientific Review Board, Medical Advisory Board and ad hoc
distinguished scientists (No HHMI Investigators participate in the review)
“The Howard Hughes Medical Institute expects not only that its investigators be talented and productive scientists, but also that they demonstrate some combination of the following attributes to an extent that clearly distinguishes them from other highly competent researchers in their field: (1) They identify and pursue significant biological questions in a rigorous and deep manner. (2) They push their chosen research field into new areas of inquiry, being consistently at its forefront. (3) They develop new tools and methods that enable creative experimental approaches to biological questions, bringing to bear, when necessary, concepts or techniques from other disciplines. (4) They forge links between basic biology and medicine. (5) They demonstrate great promise of future original and innovative contributions.”
What are the criteria for an investigator review?
A shorthand way of defining the criteria: the “deletion test”
Scientific Review Process
Addresses the current five year appointment period
Investigators submit curriculum vitae, bibliography, progress report and
description of future plans, and five significant publications
At HHMI Headquarters, each investigator makes a 35-minute presentation
Advisors and investigator have a 20-minute question and discussion period
Advisors meet in executive session to develop a consensus recommendation
HHMI leadership uses recommendation to make final reappointment decision
Successful review: five-year renewable appointment
Unsuccessful review: two-year nonrenewable term
Investigator Review Outcomes: 2000 - 2011
Year # Reviews # Terminated % Terminated
2000 28 5 18
2001 36 7 19
2002 65 17 26
2003 67 16 24
2004 74 14 19
2005 58 6 10
2006 30 4 13
2007 60 7 12
2008 41 10 24
2009 48 10 21
2010 60 12 20
2011 59 10 17
Total 626 118 19 23
Early Career Scientists
Applicants must be within 2 – 6 years of initial academic appointment Single, non-renewable appointment term of 6 years Salary and benefits covered by HHMI Annual research budgets from $150,000 – $300,000 over 6 year term Eligible for justified equipment purchases
50 Early Career Scientists selected for funding from 2100 initial applications >30 institutions represented among the finalists
Objective
Identify important biomedical problems for which future progress requires technological innovation and then foster the establishment of integrated teams of biologists and tool builders who seek to break through the existing barriers.
Recruitment
Neurobiologists
Molecular biologists
Chemists
Geneticists
Physicists
Instrument designers/engineers
Computer scientists/mathematicians
To accomplish these goals, JFRC recruits
Current Research at JFRC
Two synergistic objectives:
Identify general principles that govern how information is processed by groups of neurons
Develop enabling imaging technologies
JFRC Scientific Staff under initial 5 year plan:
24 Group leaders (20 as of today)
20 Fellows (19 as of today)
Senior Fellows (5 as of today)
Applied Physics and Instrumentation Group
Visitors and Project Teams (53 active projects)
Graduate student program (21)
Junior Fellow (independent postdoctorals; 4)
Shared Scientific Support (8 different) Scientific Computing (20)
Instrument Design and Fabrication (14)
Optical Microscopy with Resolution of Electron Microscopy
Figure 1A: A high-resolution optical microscope image of a fluorescently labeled Golgi in a cell, demonstrating the limits of optical resolution. 1B: The same area imaged and processed by the PALM approach, resulting in significantly higher resolution.
New Directions for JFRC: Structural Biology, with an emphasis on Cryo-Electron Microscopy Stephen Harrison, Richard Henderson, Roderick MacKinnon, Eva Nogales & Thomas Walz, advisors Development and Evolution of Nervous Systems Sydney Brenner, Sean Carroll & Larry Zipursky, advisors Cell Biology of Neurons
Karel Svoboda, Mary Kennedy & Michael Greenberg, advisors
Hughes Collaborative Innovation Award Program
HCIA Program supports innovative, collaborative projects led by HHMI investigators with collaborators including non-HHMI and international scientists
Current program supports 8 projects for four years each (2008-2012), with an annual budget of ~$1.2M ($10M/year)
Examples of funded projects:
- Peter Walter: Deciphering the role of the unfolded protein response in disease
- Xiaowei Zhuang: Wiring diagrams of mammalian brain
- Simon John: An implantable ultra-miniature sensor with remote interrogation system
Catherine Dulac, Ph.D. HHMI Investigator Harvard University How Does Gene Imprinting Shape Behavior and Brain Development?
Simon John, Ph.D. HHMI Investigator Jackson Laboratory Developing a Tiny, Wireless Sensor to Monitor Glaucoma Around the Clock
Danny Reinberg, Ph.D. HHMI Investigator New York University School of Medicine What Can Ants Teach Us About Aging and Behavior?
Collaborative Innovator Awards: Project Leaders
Susan Lindquist, Ph.D. HHMI Investigator Whitehead Institute for Biomedical Research Discovering New Strategies to Treat Neurodegenerative Diseases
Douglas C. Rees, Ph.D. HHMI Investigator California Institute of Technology Building a Better Foundation for Structural Studies of Membrane Proteins
Xiaowei Zhuang, Ph.D. HHMI Investigator Harvard University A Better Wiring Guide to the Mammalian Brain
Huda Y. Zoghbi, M.D. HHMI Investigator Baylor College of Medicine Speed Scanning the Genome for Neurodegenerative Disease Therapies
Peter Walter, Ph.D. Univ. of California-San Francisco The Unfolded Protein Response: A Good Target for Drug Design?
New Competition for Hughes CIA Projects
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Competition announced December 2, 2011
Project leader must be an HHMI investigator
Collaborators may be ECS, HHMI investigator, non-HHMI and international
4 year projects; typically ~$1.1M annual budget
71 proposals submitted by March 13, 2012
Selection of funded projects by July 1, 2012
Project funding to begin on or after Sept. 1, 2012