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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
(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
1
+
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 [email protected] (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
1
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
M
HelperT cell
B cellCD8T cell
DC
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
M
HelperT cell
Ca2+
Ca2+
Ca2+Ca2+
Examining memory cell generation to infection
Engineering soluble high affinity T cell receptors
Measuring T cell activation with calcium influx
①
②
③
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
2500
5000
7500
10000
12500
15000
17500
LLO118 LLO560
5000
10000
15000
20000
25000
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)
5µm
Aga2pS S
SS
Aga1p
HA
scTCR
~50,000identical copies/cell
c-myc
Yeast Cell Wall
Yeast Proteins(anchors)
Fluorescent Ligand
Yeast Cell
Engineering high affinity T cell receptors
V
V
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
NFAT
Calcineurin
Nucleus
NFAT
Orai1
Ca2+Ca2+Ca2+
Ca2+Ca2+
Ca2+
TCRCD3
IP3
ERCa2+
Ca2+
Ca2+
Ca2+
Fertilization * Transcription * Lymphocyte activation * Muscle contraction * Cell death
Th1 Th2
Th17
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 [email protected] (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
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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
Seru
mTu
mor
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 [email protected] (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
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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
Neo
nate1
Adult
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
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 [email protected] (801) 422-7562
Areas of Interest: Cellular and molecular physiology, particularly vesicle membrane fusion in neuronal cells and its block by botulinum (botulism) toxin
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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
Axon
Neuromuscular junction
[email protected] 4Figure 4-19, Sherwood, 2001
[email protected] 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 [email protected] (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
Utah
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?
Cotton GenomicsJoshua UdallPlant & Wildlife Sciences [email protected] (801) 422‐9307
Areas of Interest: Genome research on cotton, raspberry, sagebrush, lupin
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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
Gen
e abun
dance SelectionG. hirsutum
G. barbadense
G. arboreum
Overlap region present in 454 and Sanger reads
New overlaps discovered in Illumina reads
