Table of Contents - Research...

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Page #’s Title Name Department

2-5 Educational Research in the Life Sciences Jamie Jensen Biology

6-16 Helper T cell role in immunity to infection Scott Weber Microbiology and Molecular Biology

17-34 Cancer Research Kim O'Neill Microbiology and Molecular Biology

35-42 Molecular Pathways of Beta-cell Function and Proliferation Jeffery Tessem Nutrition, Dietetics and Food Science

43-51 Molecular Mechanisms of Exocytosis (Neurosecretion) Dixon Woodbury Physiology and Developmental Biology

52-70 Agave – Exploring the Native Ecology and Historic Uses of a Tough but Promising Succulent Crop Ryan Stewart Plant & Wildlife Sciences

71-75 Cotton Genomics Joshua Udall Plant & Wildlife Sciences

Table of Contents

Educational Research in the Life Sciences

Jamie Jensen

Biology

drjbiology@gmail.com

(801) 422-6896

Areas of Interest: The development and transferability of scientific reasoning skills; appropriate assessment techniques; effective strategies for constructivist teaching in the STEM classroom; strategies to enhance STEM retention

Jamie JensenDepartment of BiologyEducational Researcher

+Focus of Study

The development and transferability of scientific reasoning skills

Appropriate assessment techniques

Effective strategies for constructivist teaching in the STEM classroom

Strategies to enhance STEM retention

+Looking for collaborators who are…

In any STEM discipline

Interested in improving undergraduate education (with a special emphasis on introductory courses)

Interested in improving underlying thinking skills, rather than just content retention

Interested in a novel approach to teaching and want some help evaluating it!

Helper T cell role in Immunity to InfectionScott WeberMicrobiology and Molecular Biology scott_weber@byu.edu (801) 422-6259

Areas of Interest: Immunology; host-pathogen interactions; molecular biology; mechanisms of T cell activation and memory cell formation; high affinity T cell receptors

Scott Weber Microbiology and Molecular Biology

Brigham Young University

Helper T cell role in immunity to infection

Central role of helper T cells in immunity to infection

HelperT cell

B cellCD8T cell

T cell activation controlled on numerous levels

1) T cell receptor: T cell function dependent upon affinity of TCR-peptide MHC2) Cell signaling: Signaling cascade regulates the T cell response to antigen3) Co-receptors: Co-receptors have a critical role in T cell inhibition and activation

HelperT cell

Ca2+Ca2+

Examining memory cell generation to infection

Engineering soluble high affinity T cell receptors

Measuring T cell activation with calcium influx

Two TCR transgenic mice specific for Listeria

LLO118 LLO56

LLO118LLO190-205/I-Ab

Vα2, Vβ2

LLO56LLO190-205/I-Ab

Vα2, Vβ2

TCRtg mice

CD4+ cells CD4+ cells

LLO118 Ly5.1 LLO56 Thy1.1TCRs differ by 15 amino acids (10 in the CDR3β)

LLO118 LLO560

Key finding: LLO118 better in primary response and LLO56 better in secondary response

Primary Response Secondary Response

Weber et al (2012) Proceedings of the National Academy of Science

- How can helper T cell memory formation be improved? - What role does cell death have on memory cell generation? - How does TCR affinity affect recognition of infectious agents?- What is the role of nucleosome epigenics in T cell function?

Protein engineering using yeast display

HA V V c-myc

Why use yeast display? 1) Generate therapeutic and diagnostic reagents. 2) Increase biological understanding of T cell activation. 3) Stabilized TCRs are amenable to affinity and structural studies

Single chain T cell receptor (scTCR)

Aga2pS S

~50,000identical copies/cell

Yeast Cell Wall

Yeast Proteins(anchors)

Fluorescent Ligand

Yeast Cell

Engineering high affinity T cell receptors

Weber et al (2005) Proceedings of the National Academy of Science

High affinity T cell receptor

Cytokine (pro or anti-inflammatory)

- How is T cell activation altered when TCR affinity is increased?- Can high affinity TCRs be immunoregulatory therapeutics?

Calcium ions are involved in numerous cellular events

Cell membrane

Calcineurin

Nucleus

Ca2+Ca2+Ca2+

Ca2+Ca2+

TCRCD3

ERCa2+

Fertilization * Transcription * Lymphocyte activation * Muscle contraction * Cell death

Th1 Th2

Measuring T cell activation with calcium influx

- How is calcium influx and T cell activation altered in memory cells and high affinity T cells?

Cancer Research

Kim O’NeillMicrobiology and Molecular Biology kim_oneill@byu.edu (801) 422-2449

Areas of Interest: Prevention of disease through research and education; Enhancing the body’s own defense systems, such as the immune system and DNA repair mechanisms; early detection of disease

Cancer Research

Dry Kim O’NeillDepartment of Microbiology and Molecular

Biology

Our Research Foci.• Unlike most research

laboratories, we focuson three main approaches:

• 1. Prevention of disease through research and education.

• 2. Enhancing the body’s own defense systems,such as the immune system and DNA repairmechanisms.

• 3. Early detection of disease.

Over 70% of cancers are preventable and could be eliminated by simply adhering to preventative measures and early detection.

The First Major Research Focus: Prevention of disease through research and education.

Prevention Through Education.• A diet rich in fruits and

vegetables will help prevent many cancers and other lifestyle diseases.

• Five a day is the well balanced way.

• What is it in fruits and vegetables that give this protective effect?’

Antioxidant Protection (Heart disease, Cancer, Stroke etc)

Apoptosis (Cancer, and neurological)

Control of gene expression (Genetic)Immune System (Diseases)

Metabolic Physiology

DNA Repair (Genetic diseases, including Cancer)Mitochondria function (Aging, memory loss, muscle tone)

Protein function (Cancer, heart, brain, etc.)

Membrane Function (Heart, Stroke)

What do the phytochemicals do?

Research TeamWe have developed many specialized test systems to research phytochemicals.

The Second Major Research Focus:

To Enhance the Bodies own Defense Systems.

• DNA Repair

• Immune system.

The ‘Comet’ assay.

• DNA can be damaged by many different mutagens and carcinogens leading to mutations which can often lead to cancer.

• Virtually every cell in the body has a DNA repair system that when efficient can fix damaged DNA and prevent the build up of mutations that lead to cancer.

• We are studying that system and seeing what we can do to improve it.

Improving the Immune system.

• Every day our body’s we produce cancer cells, but they rarely develop into cancer.

• Most cancer cells are eliminated from the body by the immune system.

• Breakdown in the immune response often leads to cancer.

How does the immune system interact with tumors?

What causes the breakdown and how can we prevent it?

•Macrophages play a major role in our body’s defense against attack from all sorts of microorganisms. •They are one of the first immune cells to respond to invasion. •What happens when they encounter tumor cells that look like normal cells? •Has the tumor the ability to stop the immune system from attacking ?

EvidenceIt has recently been shown that over 50-80% of certain breast tumors are made up of macrophages. Do the macrophages have a role in tumor progression?

Tumor Associated Macrophages• We are studying the role

of Tumor Associated Macrophages (TAMs) and their interactions with cancer cells.

Third Foci: Early Detection of Disease.

• Early detection is the key to success against cancer!

• To this end we have extensively studied the mechanisms of cancer induction and have produced a test that may allow for the early detection of all cancers.

Clinical Relevance of TK1

Using a single drop of blood…

• We are now working on development of an inexpensive, non‐invasive, early detection test using monoclonal antibodies against TK1 to use in hospitals and clinical settings.

Molecular Pathways of Beta‐cell Function and Proliferation

Jeffrey TessemNutrition, Dietetics and Food Science jeffery_tessem@byu.edu (801) 422‐9082

Areas of Interest: Delineating the molecular pathways that increase Beta‐cell proliferation; enhance glucose stimulated insulin secretion; protection against Beta‐cell death

Molecular pathways of -cell function and proliferation

Jeffery S. Tessem, Ph.D.Department of Nutrition, Dietetics and Food Science

Brigham Young University

Type 1 and Type 2 Diabetes are increasing worldwide

347 Million people world wide are diabetic

Islet transplantation-potential cure for diabetes

Major obstacle to greater use of islet transplantation is the availability of beta‐cellsMore -cells are needed

Discovery and manipulation of -cell proliferation pathways

Embryo

Obesity

Pregnancy

• Identifymolecular accelerators and brakes of beta cell replication

• Understand how these factors regulate functional beta cell mass

• Develop small molecule activators of beta cell proliferation pathways

• Apply findings to two‐state models of beta cell function (obese vs. lean,young vs. aged, male vs. female)

• Discover unique regulators of integrative metabolism

Tessem Lab-Metabolic Regulation of -cells

FM = FSR (1 + MP – MD)

FM = functional beta cell massFSR = secretion rate factorMP = change in mass due to proliferationMD = change in mass due to cell death

What is functional -cell mass?

Our experimental methodology

Adenoviral gene transfer, shRNA knockdown, pharmacological activators and inhibitors, nutritional factors

Primary rat islets Primary human isletsINS‐1 ‐cell line

Changes in proliferation rate, glucose stimulated insulin secretion, protection against apoptosis

Expression analysis and molecular, biochemical, histological techniques are used to define pathways

‐cells ‐cells

Nkx6.1Nkx6.1

Increased Functional ‐cell Mass

Genes upstreamof Nkx6.1

Genes upstreamof Nkx6.1 Early Nkx6.1

TargetsEarly Nkx6.1

Targets

Nr4a1/Nr4a3Nr4a1/Nr4a3

VGFVGF

Nr4a TargetsNr4a Targets

GSISGSIS

Carrie DraneyCarrie Draney Jason RayDoug WallJason RayDoug Wall

Andrew StratfordMark Schlerf

Amanda Hobson

Andrew StratfordMark Schlerf

Amanda HobsonJordan Tingey Steve ShepherdJordan Tingey Steve Shepherd

Molecular Mechanisms of Exocytosis (Neurosecretion)

Dixon WoodburyPhysiology and Developmental Biology dixon_woodbury@byu.edu (801) 422-7562

Areas of Interest: Cellular and molecular physiology, particularly vesicle membrane fusion in neuronal cells and its block by botulinum (botulism) toxin

dixon_woodbury@byu.edu 2

Cell Biology

Areas of Focus

• Molecular mechanisms of exocytosis (neurosecretion)

Neuroscience

Dr. Dixon J. Woodbury,Ph.D.Biophysics Great Lab

Department of Physiology and Developmental Biology

dixon woodbury@byu edu3

Mammalian Motor Neuron

Motor neuron

Muscle fiber

Neuromuscular junction

dixon_woodbury@byu.edu 4Figure 4-19, Sherwood, 2001

dixon_woodbury@byu.edu 5Figure 5 from: Weber et al. (1998) Cell 92:759-72.

Plasma (target) Membrane

v- and t- SNARE proteins: Membrane Fusion Machinery

Figure 5 From Sutton et al., Nature 395:347

TeNT=Tetanus neurotoxinBoNt=Botulism neutotoxin

Cysteine rich domain anchors SNAP25 to the membrane via palmitoylation

Palmitoylation is a reversible post-translational modification of a protein which results in attaching the sixteen carbon saturated fatty acid palmitate to the thiol group of the cysteine amino acids

C C C C

SNAP25 has three isoforms found in different parts of

the body:

Oxidation of SNAP-25 protects it from proteolytic clip by BoNT/E

SDS-PAGE analysis of

BoNT/E clipping of SNAP-25.

Clip time

Techniques used in Dr. Woodbury’s Lab: • Mammalian protein expression by plasmid transfection in bacteria • Circular Dichroism (Protein secondary structure)• Mass Spec. (Dr. Prince – post-translational modification)• Functional assay for activity by Botulinum toxins. • Cysteine Biotinylation Assay (detection of reduced cysteines)• Redox states of Proteins with cysteines (Dr. Watt – eQCM and

cyclic voltammetry)• Differential Scanning Calorimetry (protein-lipid interactions)• Molecular modeling (Drs. Busath and Grubmȕller – SNARE

complex)• Dynamic Light Scattering (size of lipid vesicles)• Planar Lipid Bilayers (assay for fusion of vesicles to membranes)

Agave – Exploring the Native Ecology and Historic Uses of a Tough but Promising

Succulent CropJ. Ryan StewartPlant & Wildlife Sciences ryan.stewart@byu.edu (801) 422‐7984

Areas of Interest: Evaluations of survival, productivity, and water relations of agaves and other succulents; greenhouse‐based study to determine whether agaves are facultative CAM plants; prediction of population locations of A. utahensis; legacy effects of Agave roasting pits and rock fields; micropropagationof A. utahensis 1

Agave – exploring the native ecology and historic uses of a tough

but promising succulent crop

J. Ryan StewartDepartment of Plant and Wildlife

Sciences

Agave L.• Evolved 7-10 mya in

Mexico• ~166 species

– 125 spp. native to Mexico– 15 spp. native to. U.S.

Southwest– Remaining spp. found in

South America and Caribbean

Ἀγαύη …A noble and admirable group of plants!

Agave palmeri Agave parryi

Agave subgenus

Littaea subgenus

Agave utahensis

Adapted to semi-arid and arid environments– Semelparous flowering– Succulent, funnel-shaped rosettes

Aguamiel

Tequila/Mescal

Henequén fiber

Roasted agave heart

Ancient Agave roasting pit

Bioenergy

Ornamental

Alternative sweetener

Medicine

Agave utahensis Engelm.(Utah agave)

Nevada

California

Arizona

Benson and Darrow, 1981

Agave utahensis native distribution

Research projects1. Common garden study to evaluate survival,

productivity, and water relations of agaves and other succulents

– Agave nectar (syrup)– Aguamiel– Bioenergy

2. Greenhouse-based study to determine whether agaves are facultative CAM plants

– Determine the transition between C3 and Crassulaceanacid metabolism photosynthetic pathways

3. Prediction of population locations of A. utahensis4. Legacy effects of Agave roasting pits and rock fields 5. Micropropagation of A. utahensis6. Other projects

Agave survival, water relations, and productivity

• Three common garden plots– Spanish Fork, Utah– Holden, Utah– St. George, Utah

• Several Agave species and other succulents

• Potential crop uses– Agave nectar (syrup)– Aguamiel– Bioenergy

Agaves – tightwads or gluttons?• Due to unique photosynthetic pathway

(crassulacean acid metabolism), characterized as extremely water-efficient

• However, many consider agaves to be high-yielding (>30 metric tons/hectare)

• Can you have your cake and eat it, too?• Preliminary data suggests “Au contraire

mon frere!”• Agaves very likely facultative CAM plants

Agave rock fields – does the past hold the key to the future?

• Warming trends due to climate change suggest that native range of agaves could expand northward

• Indigenous peoples in Southwest cultivated agaves for hundreds of years in rock fields

• Could study of underlying biogeochemistry of rock fields provide insight in determining impacts of agaves in natural and human systems?

Ryan Stewart167 WIDB

rstewart@byu.edu801.422.7984

Cotton GenomicsJoshua UdallPlant & Wildlife Sciences jaudall1@gmail.com (801) 422‐9307

Areas of Interest: Genome research on cotton, raspberry, sagebrush, lupin

Cotton Genomics

Joshua UdallPlant and Wildlife Science

Department

1700 MB 900 MB

A framework for studying polyploidy in Gossypium

Effects of polyploidy and domestication on cotton nucleotide diversity

Wild forms

First cultivars

Landraces Modern cultivars

Nucleotide Diversity

e abun

dance SelectionG. hirsutum

G. barbadense

G. arboreum

Overlap region present in 454 and Sanger reads

New overlaps discovered in Illumina reads

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