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SHAWN AHMED LAB

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Page 1: SHAWN AHMED LAB - bgsa.web.unc.edu

SHAWN AHMED LAB

Page 2: SHAWN AHMED LAB - bgsa.web.unc.edu

Current Research Question:

Can germ cells transmit forms of stress whose effects are as severe as

starvation?

- chromosome ends

- ‘heritable stress’

The Ahmed lab studies:

Page 3: SHAWN AHMED LAB - bgsa.web.unc.edu

VICTORIA BAUTCH LAB

Page 4: SHAWN AHMED LAB - bgsa.web.unc.edu

John Pelton Bautch Lab

Blood vessel sprouts have established

apical-basal polarity

Two endothelial cells overlap at the distal

end of sprouts

Blood Vessel Polarity is Established Via Tip Cell Overlap in New Sprouts

Blood vessel lumen formation correlates with cellular overlap

Page 5: SHAWN AHMED LAB - bgsa.web.unc.edu

JOHN BRUNO LAB

Page 6: SHAWN AHMED LAB - bgsa.web.unc.edu

John Bruno: Marine Biodiversity

Page 7: SHAWN AHMED LAB - bgsa.web.unc.edu

Abel Valdivia

BRUNO LAB

My dissertation research aims to understand how overfishing is modifying coral reefs and how the consequences of this impact affect biodiversity and ecosystem functioning. Overfishing remains the most prevalent anthropogenic disturbance in the oceans and predators are especially vulnerable. Therefore we ask a fundamental question: what is the role of predators in natural systems and how the loss of predators alter the structure, diversity and stability of coral reefs under other stressors like pollution and climate change?

MR

BC

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NC

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MC

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TO

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PO

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AL

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CP

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MW

GH

HM PZ

BC

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LG

GC

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Apex predatorPiscivore-InvertivoreInvertivoreOmnivoreHerbivorePlanktivore

Site Codesfish

bio

ma

ss

gm

2

0

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* *

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marine reserves

*

fishing pressure

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Lindsey Carr

Bruno Lab

How temperature affects green urchin grazing rates and algal community dynamics in the Galapagos Islands

Lindsey Carr

Page 9: SHAWN AHMED LAB - bgsa.web.unc.edu

CHRISTINA BURCH LAB

Page 10: SHAWN AHMED LAB - bgsa.web.unc.edu

2nd year PhD student Burch Lab

Kayla is interested in mutation rates, robustness, evolvability, and virus evolution. Her current projects include:

Elevating coronavirus mutation rates until they mutate to death

Evolving robustness in gene networks under both asexual and sexual reproduction

Modeling the evolution rate of influenza based on within-host parameters

Page 11: SHAWN AHMED LAB - bgsa.web.unc.edu

Competition and novel resource use in a virus: Using an experimental evolution approach in the bacteriophage ϕ6, I am testing the role of competition on the evolution of novel resource (host) use.

• Competition promotes the evolution of a novel resource-use phenotype.

• Coexistence between the alternative resource-use phenotypes only occurs when fitness trade-offs evolve.

• These phenotypes are currently being further evolved to test the process of ecological speciation.

Burch and D. Pfennig Labs

Lisa Bono

Page 12: SHAWN AHMED LAB - bgsa.web.unc.edu

SABRINA BURMEISTER LAB

Page 13: SHAWN AHMED LAB - bgsa.web.unc.edu

Hormonal

OH

O

Neural

Molecular

Receiver

Signaler

Signal production Behavioral Response

The Burmeister Lab

The Neurobiology of Social Signaling

Page 14: SHAWN AHMED LAB - bgsa.web.unc.edu

Yuxiang Liu 刘宇翔

Burmeister Lab

Spatial memory of frog

Page 15: SHAWN AHMED LAB - bgsa.web.unc.edu

FRANK CONLON LAB

Page 16: SHAWN AHMED LAB - bgsa.web.unc.edu

Conlon Lab

University of North Carolina

Department of Biology

UNC McAllister Heart Institute

Page 17: SHAWN AHMED LAB - bgsa.web.unc.edu

Conlon Lab

Conlon Lab Past Members

Sarah Goetz (Sloan/Kettering) Yvette Langdon (U. Penn) Kathleen Christine (MIT)

Elizabeth Mandel (Max-Planck Freiburg, Germany)

Daniel Brown (Carnegie Institute) Chris Showell (Start Up Company)

Jackie Swanik (Wake Tech)

Work was funded by grants from NIH/NHLBI,NIH/NIDCR,

American Heart Association, and NCBC

Present Lab Members Stephen Sojka Kerry Dorr Marta Szmacinski Erin Kaltenbrun Lauren Kuchenbrod Panna Tandon Lauren Waldron Nirav Amin Leslie Kennedy Chris Slagle

Page 18: SHAWN AHMED LAB - bgsa.web.unc.edu

Characterizing the Major Transcriptional complexes of Early Heart Vertebrate Development

Eomes Mesp1/2

Tbx20 Tbx5 Nkx2.5 GATA 4/6

Castor

Tcf21

(Eomes: Chris Slagle)

(Tbx20: Erin Kaltenbrun, Lauren Kuchenbrod and Leslie Kennedy) (Tbx5: Lauren Waldron and Lauren Kuchenbrod) (Nkx2.5 and Gata4: Willian Pu, Harvard Univeristy)

(Castor: Stephen Sojka and Marta Szmacinski)

(Tcf21: Panna Tandon)

Page 19: SHAWN AHMED LAB - bgsa.web.unc.edu

Isolation of the Cardiac Specific Complexes From ES Cell Induced Cardiomocytes

Example of the TBX20 Complex Characterization

ES Cells Are Induced Into Cardiomyocytes

Identification of Tbx20 Targets by ChIP-Seq

ES Cell Cardiomyocyte

Page 20: SHAWN AHMED LAB - bgsa.web.unc.edu

Systems Based Approach for the Isolation of Cardiac Complexes

Early Cardiac Tissue or Embryonic Stem Cells Induced Into Cardiomoycytes

Harvest and freeze cells

Cryogenic Lysis

Separation

Identification (LC-MS/MS)

TBX20-EGFP (Coomassie Stain) IP (αGFP)

Page 21: SHAWN AHMED LAB - bgsa.web.unc.edu

Tbx20 interacts with the TLE/GRO complex

Page 22: SHAWN AHMED LAB - bgsa.web.unc.edu

Lauren Waldron

Frank Conlon Lab

-Cardiac transcription factor TBX5

- Congenital heart disease Holt-Oram Syndrome

- New function for transcriptional activator TBX5 through interaction with

transcriptional repressor NuRD complex in the adult heart

Mi-2β RBBP4

HDAC2 MTA 1

GATAD2A

TBX5

Page 23: SHAWN AHMED LAB - bgsa.web.unc.edu

GREGORY COPENHAVER LAB

Page 24: SHAWN AHMED LAB - bgsa.web.unc.edu

Gregory P. Copenhaver

Copenhaver Lab

My lab is primarily interested in understanding how meiotic recombination is regulated at the genomic level in higher eukaryotes. The regulation of recombination ensures proper chromosome segregation and influences allelic diversity a the population level. Errors in regulating recombination result in human diseases including cancer and chromosomal abnormalities. Conversely, understanding the mechanisms that direct recombination opens the door to an array of biotechnological advances. We use the model system Arabidopsis thaliana to explore both genetic and epigenetic levels of control. To the left, meiotic groupings of male gametes (pollen) expressing different fluorescent marker proteins are shown. We use this visually striking system to quantitatively measure a variety of key meiotic phenomenon including genetic exchange, gene conversion and chromosome segregation.

Page 25: SHAWN AHMED LAB - bgsa.web.unc.edu

STEPHEN CREWS LAB

Page 26: SHAWN AHMED LAB - bgsa.web.unc.edu

Control of Drosophila CNS Development

Stephen Crews Lab

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Generation of Neuronal Formation and Differentiation

Stephen Crews Lab

Alexandra Balaban

Sunny Patel

Stephanie Stagg

Joseph Watson

Page 28: SHAWN AHMED LAB - bgsa.web.unc.edu

Regulation of Glial Cell Development and Function

Stephen Crews Lab

AMG * PMG * runt en

Joseph Watson

Scott Wheeler

Page 29: SHAWN AHMED LAB - bgsa.web.unc.edu

Control and Evolution of CNS-Specific Gene Expression

Stephen Crews Lab

Joe Pearson

link-5’

link-5’-mutT134

Page 30: SHAWN AHMED LAB - bgsa.web.unc.edu

Neuronal and Glial Migration and Axon:Glial Interactions

Stephen Crews Lab

Rachel Tyson

Joseph Watson

Scott Wheeler

Page 31: SHAWN AHMED LAB - bgsa.web.unc.edu

Diversity of Neural Function and Connectivity

Stephen Crews Lab

Joe Fontana

Nivi Umasankar

SIG IG IG TM

Page 32: SHAWN AHMED LAB - bgsa.web.unc.edu

MARA DUNCAN LAB

Page 33: SHAWN AHMED LAB - bgsa.web.unc.edu

The Duncan Lab

Investigating the roles of membrane traffic in cell physiology

Endosomal traffic provides food for a starving cell

ATP reshapes endosomal traffic

ATP

Endosomal traffic regulates cell signaling

Page 34: SHAWN AHMED LAB - bgsa.web.unc.edu

ROBERT DURONIO LAB

Page 35: SHAWN AHMED LAB - bgsa.web.unc.edu

Duronio & Marzluff Labs

Histone mRNA

Regulation in

Drosophila

Development

histone locus

body (HLB)

Page 36: SHAWN AHMED LAB - bgsa.web.unc.edu

Joy Meserve, Duronio Lab

Investigating cell cycle re-entry following damage using an RNAi screen in the developing Drosophila eye disc

TF RNAi?

Wild type adult eye

Page 37: SHAWN AHMED LAB - bgsa.web.unc.edu

Studying The Organization And Function Of The Drosophila melanogaster Histone Locus Body (HLB)

Este Terzo

Duronio Lab

Page 38: SHAWN AHMED LAB - bgsa.web.unc.edu

PAT GENSEL LAB

Page 39: SHAWN AHMED LAB - bgsa.web.unc.edu

Branching and vasculature that might

represent early leaf evolution in seed plant

line- Early Devonian (407 mya)

Fossil plant studies provide information about

morphology, innovation, diversity, and

phylogeny through time

Patricia G. Gensel, Biology Dept., UNC-Chapel Hill

Accumulated data allow for

reconstructing past environments,

here for E.Devonian, New Brunswick

Early Devonian evidence of secondary

tissues

Spore

ultrastructure is

phylogenetically

informative

Page 40: SHAWN AHMED LAB - bgsa.web.unc.edu

BOB GOLDSTEIN LAB

Page 41: SHAWN AHMED LAB - bgsa.web.unc.edu

Bob Goldstein

Goldstein lab

We use C. elegans to discover fundamental mechanisms in cell and developmental biology.

We’re also developing water bears as a new model for studying how such mechanisms evolve.

Page 42: SHAWN AHMED LAB - bgsa.web.unc.edu

SARAH GRANT LAB

Page 43: SHAWN AHMED LAB - bgsa.web.unc.edu

Tatiana Mucyn, Scott Yourstone, Surge Biswas, Abigail Lind, Corbin Jones, Jeff Dangl and Sarah Grant

Pseudomonas syringae is a Gram-negative bacterial plant pathogen with high phylogenic diversity responsible for

worldwide disease on many crop species.

HrpL is the master regulatory transcription factor of P. syringae that controls expression of the genes encoding the

structural and regulatory components of the type III secretion system, essential for virulence, and expression of the type III

secreted effectors.

We implemented and refined transcriptional analysis methods using cDNA derived high-throughput short read sequencing

data (RNA-seq) to identify the HrpL-regulated genes for six isolates of P. syringae, that represent the diversity of the

species.

Comparative analysis of the HrpL-regulons highlighted strain-specific variability in the secreted type III effectors and in

genes for non-secreted HrpL-regulated proteins including operons which produce secondary metabolites. Some of these

operons have been shown to be required for virulence on the natural host but the functions of the majority of HrpL-

regulated genes for non-secreted proteins remain to be characterized.

Comparative analysis of HrpL regulons of diverse

Pseudomonas syringae reveals novel virulence factors.

Nu

mb

er

of

Hrp

L-r

eg

ula

ted

ge

ne

s

P. syringae isolates

Predicted gene functions

Sarah Grant

Page 44: SHAWN AHMED LAB - bgsa.web.unc.edu

TY HEDRICK LAB

Page 45: SHAWN AHMED LAB - bgsa.web.unc.edu

Ty Hedrick

Hedrick lab

Biomechanics, Comparative Physiology and Behavior Aerodynamics Control and Stability in locomotion Group behavior and flocking Muscle physiology Neuromuscular control of movement Neurosensory systems

Moth perturbation

Swal

low

tan

dem

flig

ht

Page 46: SHAWN AHMED LAB - bgsa.web.unc.edu

ALLEN HURLBERT LAB

Page 47: SHAWN AHMED LAB - bgsa.web.unc.edu

Allen Hurlbert

HURLBERT LAB

biodiversity patterns, biogeography, climate change, citizen science

Page 48: SHAWN AHMED LAB - bgsa.web.unc.edu

Jes Coyle

Hurlbert Lab

Understanding spatial variation in

the properties of ecological

communities

Page 49: SHAWN AHMED LAB - bgsa.web.unc.edu

ALAN JONES LAB

Page 50: SHAWN AHMED LAB - bgsa.web.unc.edu

Alan M. Jones

Alan Jones Lab

Page 51: SHAWN AHMED LAB - bgsa.web.unc.edu

Alejandro received his PhD in molecular biology at the University of Buenos Aires, Argentina; he has joined the lab as a postdoc in August 2011. His main interest is to study the role of G proteins in the epigeneticresponses of Arabidopsis to environmental stress.

The impact of Drought in Arabidopsis CpG methylation

ALEJANDRO COLANERI

Alan Jones Lab

Page 52: SHAWN AHMED LAB - bgsa.web.unc.edu

Daisuke Urano

Alan Jones lab

I research diversity of heterotrimeric G-protein pathways. My research field ranges from animals and plants to some basic single cellular eukaryotes. I also research plant G-protein pathway using liverworts, an genetic model of evolutionary intermediate plants.

Page 53: SHAWN AHMED LAB - bgsa.web.unc.edu

Jian-Ping Huang (Jenny)

Jenny is a research collaborator from Northeast Agricultural University in China . She is studying on the integration of HXK1-dependent and RGS1-dependent glucose signal transduction pathways in Arabidopsis thaliana.

Alan Jones Lab

Page 54: SHAWN AHMED LAB - bgsa.web.unc.edu

Meral Tunc-Ozdemir

Meral Tunc- Ozdemir is a postdoctoral Research Associate; she joined the lab in November, 2012. She is interested in understanding the heterotrimeric G protein signalling network upon recognition of plant pathogens.

Alan Jones Lab flg22

AtRGS1

BIR1 BAK1

Page 55: SHAWN AHMED LAB - bgsa.web.unc.edu

Nguyen Phan

Nguyen Phan is a postdoctoral researcher. He works on the genetics, cellular trafficking and signal transduction of G protein in Arabidopsis.

Alan Jones Lab

Page 56: SHAWN AHMED LAB - bgsa.web.unc.edu

Susanne Wolfenstetter

Susanne Wolfenstetter is a postdoctoral Research Scholar; she joined in October, 2012. She is investigating the mechanism of plant G protein activation in response to different extracellular stimuli

Alan Jones Lab

Page 57: SHAWN AHMED LAB - bgsa.web.unc.edu

Wenli (Wendy) Chen

Wen Li is a visiting scholar from South China Normal University in China; she joined in May, 2013. She is interested in researching the role of autophagy in G protein-dependent nutrient sensing in Arabidopsis using genetic studies, molecular biology and LSCM.

Alan Jones Lab

Page 58: SHAWN AHMED LAB - bgsa.web.unc.edu

Yan Fu

Alan Jones Lab

Yan is a postdoc working on building quantitative mathematical model of G protein activation system in Arabidopsis. Her current research focus on how plant cells decode patterns (e.g. intensity and sustainability) of sugar signals and respond with specificity.

Page 59: SHAWN AHMED LAB - bgsa.web.unc.edu

Yashwanti Mudgil a visiting scholar from Delhi University in INDIA; she joined in Sept , 2012. She is interested in researching the role of NDL proteins in G protein-dependent stress sensing in Arabidopsis using genetic and biochemical approaches.

Alan Jones Lab

Yash Mudgil

Page 60: SHAWN AHMED LAB - bgsa.web.unc.edu

CORBIN JONES LAB

Page 61: SHAWN AHMED LAB - bgsa.web.unc.edu

Artur Romanchuk

• Corbin D. Jones lab

Although organisms vary dramatically, molecular pathway

structure, and interactions between genes are conserved. This

suggests common constrains on gene gain. How can genes

appear without disrupting existing molecular

pathways?

I focus on gene connectivity within molecular pathway

topology and how molecular pathway topology influence gene

gain.

Page 62: SHAWN AHMED LAB - bgsa.web.unc.edu

Eric Earley

Corbin Jones Lab

Genetics of food preference evolution in Drosophila

Genomic methods in mapping complex phenotypes

Page 63: SHAWN AHMED LAB - bgsa.web.unc.edu

BILL KIER LAB

Page 64: SHAWN AHMED LAB - bgsa.web.unc.edu

Bill Kier

Comparative Biomechanics

-Functional morphology of musculoskeletal systems

-Structure, function, development and evolution of muscle

-Biologically inspired robotics

Page 65: SHAWN AHMED LAB - bgsa.web.unc.edu

Jessica Kurth

Kier Lab

Studying effects of body size on the hydrostatic (i.e. fluid-filled) skeletons of soft-bodied invertebrates. These animals range in size from micrometers to meters long and span many taxa. Many species burrow through the soil and play important ecological and economic roles as ecosystem engineers. The effects of size on burrowing mechanics are also poorly understood. My current system is the earthworm Lumbricus terrestris.

Page 66: SHAWN AHMED LAB - bgsa.web.unc.edu

JOEL KINGSOLVER LAB

Page 67: SHAWN AHMED LAB - bgsa.web.unc.edu

Kingsolver lab Invasive species

Climate change

Selection in nature

Responding and adapting to changing environments

Page 68: SHAWN AHMED LAB - bgsa.web.unc.edu

Jessica Higgins

Kingsolver Lab

Adaptation to climate change in larval Colias butterflies.

• Research Questions

• Short Term Growth • Over what range of temperatures

can caterpillars feed and how has this changed over time?

• Long Term Growth

• How does the interaction of host plant and temperature affect larval development historically and today?

• Extreme Events

• What effect does heat shocks have on larvae?

Changing feeding rates (short term growth) and summer temperatures over 40 years. The top graphs are larval feeding rates from 1972 vs. 2012 and the bottom graphs are summer temperature densities from 1961-1971 and 2001-2011.

Page 69: SHAWN AHMED LAB - bgsa.web.unc.edu

ALAIN LAEDERACH LAB

Page 70: SHAWN AHMED LAB - bgsa.web.unc.edu

Laederach Lab

• Understanding the relationship between RNA structure and folding dynamics

• Applying cutting edge computational and experimental techniques to understand the role of SNPs occurring in UTRs in human disease and advance personalized medicine

Charles

Zack

Dry lab Wet lab

Jasmin

Chas Katrina Justin

Matt Kevin

Gabi

Wes

Alex

Amanda CPU - Alain

Page 71: SHAWN AHMED LAB - bgsa.web.unc.edu

Gabriela Phillips

Laederach Lab

1. Work in the laboratory predicts that the disease-associated C116U SNP significantly perturbs

the secondary structure of the SERPINA1 5’ UTR.

a. We are validating the predicted changes using SHAPE.

b. We will use in vitro Luciferase assays to determine whether or not changes in 5’ UTR

structure affect translation of the protein.

2. Using random mutagenesis and deep sequencing, we are creating a library to identify all

mutations in the 5’ UTR of SERPINA1 that could potentially induce a large conformational

change in the mRNA.

SERPINA1 and COPD

Alpha 1-antitrypsin (A1AT) deficiency is a genetic disorder

caused by the defective production of A1AT, a protein encoded

by SERPINA1. Severe deficiency of A1AT causes many

problems including panacinar emphysema or Chronic

Obstructive Pulmonary Disease (COPD). Using the data from a

recent genome-wide association study, our laboratory identified

a SNP in the 5’ UTR of SERPINA1 associated with increased

risk of developing COPD.

Ongoing Projects

Page 72: SHAWN AHMED LAB - bgsa.web.unc.edu

JASON LIEB LAB

Page 73: SHAWN AHMED LAB - bgsa.web.unc.edu

Sheera Adar Postdoc

Jason Lieb lab

A genome-wide study of DNA repair Immunoprecipitation of DNA damage:

IPoD-seq

Higher damage levels at 3’ and 5’ ends of genes CPDs are widespread and dictated by the underlying sequence:

Experimental scheme in S.cerevisiae:

Page 74: SHAWN AHMED LAB - bgsa.web.unc.edu

Laura Simmons Kovacs Postdoc

Lieb Lab

TF

TF

TF T

urn

ove

r R

ate

Transcription Rate

TF T

urn

ove

r R

ate

Nucleosome Binding

? ?

Page 75: SHAWN AHMED LAB - bgsa.web.unc.edu

Zhuzhu Zhang

Jason Lieb Lab

How completely is the chromatin structure in human iPS cells reset to an ES-like state?

Page 76: SHAWN AHMED LAB - bgsa.web.unc.edu

Abstract Two of the canonical measurements of protein-DNA binding dynamics, Fluorescent Recovery After Photobleaching (FRAP) and competition ChIP (a unique adaptation of ChIP), give very different measurements of residency time. Despite numerous FRAP and regular ChIP measurements being taken on similar proteins, FRAP and competition ChIP measurements have never been taken in the same system and with the same protein. To get a better understanding of protein-DNA binding dynamics we have three aims.

Max Boeck

Lieb Lab

Aims 1) Reconcile the disparate residence time of FRAP and competition ChIP by taking both measurements in the same system using the same protein. 2) Better understand their relationship by taking FRAP measurements with multiple site-specific promoter arrays. 3) Understand the effect of local chromatin environment in both systems by using genome-wide miccrococcal nuclease digestion assays.

Page 77: SHAWN AHMED LAB - bgsa.web.unc.edu

Sebastian Pott

Jason Lieb lab

Somatic sequence variation in normal human tissues

• To determine number, distribution, and types of somatic sequence variants in human tissues • To correlate tissue-specific features of somatic sequence variation with cancer prevalence of tissues • To identify (tissue-specific) determinants of somatic mutations in normal tissues

sequencing

Page 78: SHAWN AHMED LAB - bgsa.web.unc.edu

Shehzad Sheikh MD, PhD Assistant Professor of

Medicine

Jason D. Lieb

Characterizing non-coding DNA variants

in Inflammatory Bowel Disease (IBD)

Hypothesis: IBD single nucleotide polymorphisms (SNPs) in open chromatin regions are DNA regulatory elements that are active in and relevant to IBD pathogenesis, and are causal SNPs that are more likely to directly mediate chronic intestinal inflammation. Methods: Determine chromatin status throughout the genome in colon tissue harvested from patients with IBD by FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements), and RNA analysis for gene expression, combined with Illumina high-throughput sequencing. Impact: To study the influence that non-coding DNA variants (SNPs) have on the phenotype of human IBD as individual variations in disease extent, severity and response to therapy.

Page 79: SHAWN AHMED LAB - bgsa.web.unc.edu

C. elegans gamete chromatin organization

-Nucleosome positioning in oocytes and sperm

- Transgenerational inheritance of histone modifications

-Genome-wide localization of gamete-specific histone H1 variants

Tess Jeffers Bioinformatics and Computational Biology

Lieb Lab

Page 80: SHAWN AHMED LAB - bgsa.web.unc.edu

KEN LOHMANN LAB

Page 81: SHAWN AHMED LAB - bgsa.web.unc.edu

Geomagnetic Navigation, Migration, and

Sensory Biology in Marine Animals

Lohmann Lab

Department of Biology

Univ. of North Carolina

Chapel Hill, North Carolina

U.S.A.

Page 82: SHAWN AHMED LAB - bgsa.web.unc.edu

WILLIAM MARZLUFF LAB

Page 83: SHAWN AHMED LAB - bgsa.web.unc.edu

Control of Mammalian Histone mRNA Metabolism

William Marzluff

Page 84: SHAWN AHMED LAB - bgsa.web.unc.edu

GREGORY MATERA LAB

Page 85: SHAWN AHMED LAB - bgsa.web.unc.edu

Kavita Praveen

Matera Lab

Understanding the etiology of SMA using Drosophila melanogaster

SMA is a lethal childhood neuromuscular disorder

Caused by mutations in Survival motor neuron 1 (SMN1)

How do mutations in SMN1 lead to SMA? Create SMA patient-derived point mutations in

Drosophila Smn gene

Locomotion/Behavioral assays RNA

Sequencing

Viability/longevity assays

Proteomics SMA point mutants

Page 86: SHAWN AHMED LAB - bgsa.web.unc.edu

Matera Lab

snRNP Biogenesis and Spinal Muscular Atrophy

mRNA levels (FPKM)

Levels of minor (U12-type) inton-containing mRNAs fluctuate more over development than between Ore-R and Smn mutant

RNA-seq of Smn mutant

mRNA levels - normalized read tracks of wild-type (Ore-R) and Smn mutant

Developmental delay of Smn mutant

RNA-seq. comparison with larval developmental transcriptome

Eric Garcia, Ph.D.

Page 87: SHAWN AHMED LAB - bgsa.web.unc.edu

Zhipeng Lu

Matera Lab

Research Projects 1. Identifying novel non-coding (nc)RNAs and mRNAs

that associate with Sm-class RNA binding proteins 2. Developed algorithm for refining ncRNA ends from

RNA-seq data 3. Discovered a novel cytoplasmic organelle

E

D2 D3

B

G F

D1

SMN bodies in Spermatocytes

Sm ring

Page 88: SHAWN AHMED LAB - bgsa.web.unc.edu

Michael Meers

Matera Lab

Histone post-translational modifications play a significant role in regulating gene expression. Of particular interest to our lab is the methylation of lysine 36 in the histone H3 subunit (H3K36me), which co-transcriptionally recruits complexes that repress cryptic transcription and regulate alternative splicing. Using a ground-breaking Drosophila melanogaster histone replacement model, we are using flies with point mutations in H3K36 to study the effect of depleting H3K36me upon development, proliferation, and complex gene regulatory functions.

Nature Reviews | Molecular Cell Biology

MeMe

Me

K36

H3

MRG15

PTB

ESRP

DNA

7

FGFR2 in mesenchymal cells

IIIb IIIc 10

↑ NSD?↑ SETD2↑ ESRP

7

FGFR2 in epithelial cells

↑ ESRP↑ NSD?↑ SETD2

IIIb IIIc 10

Polypyrimidine tract-binding

protein

(PTB). A protein that has been

implicated as an antagonist of

exon definition, the action

of which results in the

repression of exon inclusion.

Fibroblast growth factor

receptor 2

(FGFR2). A membrane-bound

receptor that undergoes

alternative splicing and is

subject to regulation by

methylation of Lys36 on

histone H3.

Epithelial splicing regulatory

protein

(ESRP). An alternative splicing

factor that is enriched in

epithelial tissues and is

responsible for enforcing

specific exon inclusion.

octamer correlates with the average length of an internal

exon. This is likely to be more than just mathematica l

serendipity; it is probably evidence of interplay between

chromatin and splicing. Several large-scale bioinfor-

matics studie s have analysed both the positions of

nucleosomes and their modification status within the

genomes of humans, C. elegans, D. melanogaster and

mice79–81. In each case, nucleosomes were enriched

speci fically at exonic sequences. Although the increased

deposition of nucleosomes at exons guarantees a bias

in histone modifications within exons relative to those

within introns, it is also clear that a subset of modifica-

tions is specifically enriched here. This is particularly

true for H3K36me3 but also includes methylation at

H3K79, H4K20 and H2BK5 (REF. 80). Each analysis also

found that the H3K36me3 bias is more pronounced

within exons further downstream of the transcription

start site. This preference may reflect the propensity of

RNAPII to abort transcription early in the transcription

cycle, thereby reducing the number of nucleosomes that

are displaced further downstream. The known asso-

ciation between Set2 and the RNAPII CTD may also

further explain the particular increase in H3K36me3

signatures seen at downstream exons61,82. The impli-

cation of nucleosome enrichment and the increase in

H3K36me3 modifications is twofold. First, nucleosomes

probably act as intrinsic pause sites for elongating

RNAPII which could alter splice site recognition and,

hence, change exon inclusion. Others have found that

the introduction of pause sites within minigenes can

increase the inclusion of alternatively spliced exons83,84.

Furthermore, expression of a ‘slow’ mutant RNAPII in

D. melanogaster results in different inclusion patterns of

the exons within the Ultrabithorax mRNA85. A second

possibility, which is not mutually exclusive with effects

on RNAPII pausing, is that the H3K36me3 modifica-

tion relays a specific signal to the splicing machinery

to alter how it defines exons, leading to the specific

inclusio n or exclusion of particular exons.

Although the global analyses of H3K36me3 posi-

tioning in various genomes provide compelling evi-

dence that this modification affects splicing, functional

evidence beyond this has been lacking. However, an

interesting connection has been made between SETD2,

the reader protein MORF-related gene 15 (MRG15;

which contains a chromodomain) and polypyrimidin e

tract-binding protein (PTB), the last of which is a known

antagonist of exon definition that affects splicin g of

fibroblast growth factor receptor 2 (FGFR2) pre-mRNA86,87.

FGFR2 contains two mutually exclusive exons (II Ib

and IIIc) that encode a region within the extracellular

immunoglobulin-like domain and are each responsi-

ble for receptor binding to a unique range of FGFs88.

Exon II Ib is included in epithelial cells through the

action of epithelial splicing regulatory protein (ESRP),

whereas exon I I Ic is included in cells of mesenchy-

mal origin89 (FIG. 3). Furthermore, the splicing pattern

switches from exon IIIb to exon IIIc inclusion as pros-

tate epithelial cells become androgen-independent, an

important factor in metastasis. Analysis of nucleosome

modifications throughout FGFR2 show that H3K36me3

is specifically enriched within exon IIIb and is restricted

to mesenchymal cells, which exclude this exon. This

H3K36me3 modification is recognized by MRG15,

which also interacts with PTB. Thus, by recruiting PTB

to its target exon, these interactions position PTB to

bind to its intronic splicing silencer sites, which flank

the repressed exon as they emerge from the transcribing

RNAPII complex (FIG. 3). PTB repression of this exon

can be alleviated by downregulating either MRG15 or

SETD2. This regulatory module also exists at other

alternatively spliced exons, with a bias towards exons

that contain weaker PTB-binding sites86. What remains

to be seen is how two distinct cell types achieve this dif-

ferential methylation of H3K36 within nucleosomes at

alternatively spliced exons in order to regulate splicing.

This example of FGFR2 control exemplifies how

the methylation status of H3K36 can affect splicing.

However, this crosstalk is bidirectional: mutations in

splice sites that abrogate intron removal of β-globin

reporter genes cause a shift in H3K36me3 signatures

H3K36me3 influences alternative splicing in a cell-type specific manner.

FGFR2

influence splicing at this locus. FGFR2

REVIEWS

NATURE REVIEWS | MOLECULAR CELL BIOLOGY VOLUM E 13 | FEBRUARY 2012 | 121

© 2012 Macmillan Publishers Limited. All rights reserved

Transgenic histone mutant pupae marked by GFP expression

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• Importin-7 (Imp7) interacts with snRNP protein and RNA components in flies • Imp7 localizes to snRNP specific nuclear bodies (Cajal bodies) • Conservation of Imp7 interaction with the snRNP import adaptor, Snurportin, in

humans, and localization to Cajal bodies. • Imp7 null mutants display snRNP specific phenotypes suggesting a snRNP import defect: -Reduced survival motor neuron (SMN) protein -Reduced coilin protein (snRNP nuclear body marker) -Reduced numbers of Cajal bodies -Cytoplasmic accumulation of TMG capped snRNAs

SMN SMN SMN SMN

Amanda Natalizio

Matera Lab

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Stephen Klusza Ph.D.

Matera/Duronio Lab

The methylation of lysine 20 on the Histone 4 tail (H4K20Me) is a very intriguing histone mark, because correct deposition of the mark is dependent on a functional cell cycle. This mark is implicated in a variety of cellular processes in mammalian systems, including cell migration, replication origin licensing, DNA damage response, and chromatin packaging/architecture. We have developed a transgenic genetic array to test the roles of H4K20Me directly in Drosophila, and are currently assessing the molecular and developmental consequences of loss of this mark, with a focus on how chromosome compaction by H4K20Me influences cell-cycle dynamics and other downstream events that govern cellular processes.

Normal development of larvae with

methylated H4K20

Developmental defects in

larvae with non-

methylated H4K20

H4K20 methylation during the cell cycle

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I’m a research specialist team-­­working with Kavita Praveen, a former Ph.D student in Matera lab, on the project of Drosophila model of Spinal Muscular Atrophy.

We developed a Drosophila model system to study SMApaEent-­­derived loss-­­of-­­funcEon mutaEons in the background of an Smn null allele.

Ying Wen M.S.

SmnWT and SmnT205I Animals Have Similar snRNA ProfilesKP, YW and GM, Cell Report, 2012

Matera Lab

Drosophila model of Spinal Muscular Atrophy

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ANN MATTHYSSE LAB

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The Role of Glycoside hydrolases in the Interaction of Non-soft Rot Gram-negative Bacteria with Plant Surfaces

Ann Matthysse’s lab The interaction of Salmonella enterica typhimurium with plant surfaces

Jessica Glatz, Andrew Patterson, and Palak Patel

The interaction of Agrobacterium tumefaciens with plant surfaces Stephanie Mathews, Haylea Hannah, Hillary Samagaio, and Janice Lee

S. enterica invading the edge of a stem scar on a tomato fruit Left: bright field Right :fluorescence microscopy. Bacteria labeled with Gfp

Effect of mutations in two glycoside hydrolase genes on the binding of A. tumefaciens to tomato root hairs(left) and virulence on tomato stems (right). Arrows point to bound bacteria or to tumors. C58 (the wild-type parent strain) binds and is virulent.

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CHARLES MITCHELL LAB

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James Cronin

Mitchell Lab

My primary research area is community ecology, with emphasis on plant-insect-pathogen interactions. I am motivated by a desire to advance theory by linking patterns of phenotypic variation to population, community, and ecosystem processes. My current projects include:

• Developing tools to identify Pathogen Reservoirs

• Predicting Global Change’s influence on Disease Risk

• Explaining Herbivore and Pathogen Community Assembly

Δ Acquisition

Δ Allocation Enemy Activity

Δ Fitness

Host Developmental Tempo

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Rob Heckman

Mitchell Lab

Impacts of natural enemies on plant invasions Role of plant functional traits in response to enemies Effects of diversity on invasions

Study Systems:

Old fields

Tallgrass prairies Deciduous forest understories

Page 97: SHAWN AHMED LAB - bgsa.web.unc.edu

Erin Mordecai

Charles Mitchell Lab

Maintenance of parasite diversity. Impacts of pathogens on plant coexistence. Impact of temperature on disease transmission.

Study systems: o Barley Yellow Dwarf Viruses o Human malaria o Salt marsh trematodes o Black fingers of death fungal

pathogen

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ROBERT PEET LAB

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Peet Lab – Focal topics

1. Community assembly & diversity – Determination of patterns in diversity and community assembly relative to scale and environment.

2. Vegetation dynamics – Identification of mechanisms driving vegetation change.

3. Ecoinformatics – Examination of large-scales patterns of community assembly, and development of supporting cyber-infrastructure.

4. Vegetation classification & survey – Documentation of the vegetation of the Carolinas, and development of international standards.

Plant Community Ecology

Page 100: SHAWN AHMED LAB - bgsa.web.unc.edu

Kyle Palmquist

Peet Lab

• Vegetation dynamics over space and

time

• Scale dependence of ecological

patterns and processes

• Community assembly in grassland

ecosystems

• Maintenance of plant biodiversity

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DAVID PFENNIG LAB

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We study the interplay between evolution, ecology,

and development by investigating:

• the evolutionary and ecological implications of phenotypic

(developmental) plasticity;

• the causes and consequences of transgenerational

epigenetic inheritance;

• competition’s role in diversification;

• development and evolution of mimicry.

David Pfennig lab

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Snake Pigmentation, Coloration, and Perception by Birds

Warning signalsUltrastructureand pigments

Reflectancespectra of skin

David Kikuchi, 5th Year, D. Pfennig Lab

Between coral snakes and mimics, similarity in phenotype production This results in similar perception by birds, which are the likely agents of selection on coloration in coral snake mimicry.

For snakes with and without out a critical pigment, birds see a color difference;p = 0.0004

Co

ralS

nak

eK

ings

nak

e

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KARIN PFENNIG LAB

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We study mechanisms of behavior and the factors that

affect behavioral evolution.

Karin Pfennig lab

We focus on mate choice, because

mate choice represents one of the most

critical behaviors that can affect lifetime

fitness.

We also seek to apply our research to

solve pressing issues, ranging from the

roots of behavioral disorders to

behavior’s role in species’ invasions.

Page 106: SHAWN AHMED LAB - bgsa.web.unc.edu

Emily Schmidt

K. Pfennig Lab

Current Research: •Context-dependent mate choice in hybrid female Spea

•Development and stability of behavioral syndromes in Spea bombifrons

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TED SALMON LAB

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Ted Salmon

Kinetochores are multi-protein complexes that mechanically link chromosomes to the ends of spindle microtubules (MTs). We have developed super-resolution fluorescence microscopy methods to understand how protein architecture and conformational changes produce key kinetochore functions for dynamic-end-on-MT attachment, force production, spindle checkpoint control and correction of MT attachment error s that produce chromosome mis-segregation in anaphase.

Kinetochore

ACHIEVING ACCURATE CHROMOSOME SEGREGATION

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MT END

Core “Unit Attachment Fiber”

Ska3

Tentative Model

nm CHROMATIN

Wan et al., Cell, 2009; Varma et al., Nat. Cell Biol. 2011

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Time-Lapse of Mitotic PtK1 Cell

10 microns

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JEFF SEKELSKY LAB

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Kathryn Kohl

Sekelsky Lab

Drosophila meiotic recombination

Studying the pathways used in the regulation and formation of Drosophila

meiotic crossovers

Page 113: SHAWN AHMED LAB - bgsa.web.unc.edu

Eric Stoffregen

Sekelsky Lab

What is the role of BLM in the early Drosophila embryo?

Embryos from BLM mutant mothers undergo significant nuclear damage,

including nuclear fallout and asynchronous replication Fallout and

asynchrony

Nuclear Fallout

Nuclear Fallout

DAPI pH3 pTyr

Page 114: SHAWN AHMED LAB - bgsa.web.unc.edu

Stephanie Bellendir

Sekelsky Lab

DNA Repair and Mitotic Recombination

In vivo and in vitro analysis of the role of the Drosophila putative Holliday-junction resolvase GEN in double-strand break repair

DNA double-strand

break

Double Holliday

Junction

intermediate

Resolution

Non-crossover Crossover

?

Double-strand break repair model

GEN

GEN

Holliday junction

cleavage

Two separate DNA products

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MARIA SERVEDIO LAB

Page 116: SHAWN AHMED LAB - bgsa.web.unc.edu

Maria Servedio

Servedio lab

Many evolutionary phenomena, such as speciation, are hard to observe directly. Biologists develop verbal explanations for the roles that they believe various evolutionary mechanisms may play in these phenomena. I use mathematical models to test whether these explanations work, and to develop new ones.

Major research areas

Speciation and the evolution of premating isolation

Male mate choice

The role of learning in sexual selection and speciation

Evolutionary Theory

Page 117: SHAWN AHMED LAB - bgsa.web.unc.edu

Sumit Dhole

Servedio Lab

I study the evolution of traits involved in sperm competition and sexual selection.

I’m using mathematical models to study -

• Evolution of resource allocation by males to different seminal proteins that help in sperm competition – what proteins males make and how much of them?

• How do sperm competition traits co-evolve with traits involved in mate choice, such as male display traits?

• How do female preferences evolve for male displays that indicate good quality genes when females can also directly detect male quality.

Page 118: SHAWN AHMED LAB - bgsa.web.unc.edu

ELIZABETH SHANK LAB

Page 119: SHAWN AHMED LAB - bgsa.web.unc.edu

Elizabeth Shank

Shank Lab

Chemical signaling

Bacterial development and heterogeneity

Microbial interspecies interactions

Soil microbial ecology

Page 120: SHAWN AHMED LAB - bgsa.web.unc.edu

KEVIN SLEP LAB

Page 121: SHAWN AHMED LAB - bgsa.web.unc.edu

Jonathan Leano

Slep Lab

CLASP TOG2 Crystal Structure

Elucidating the mechanism underlining the CLASP family of proteins to regulate microtubules during interphase and mitosis

Model of CLASP TOG2 bound to tubulin monomer

Bipolar Spindle Monopolar Spindle

Wild-Type CLASP RNAi/mutant

Hyperstabilized Monopolar Spindle

CLASP overexpressed

Page 122: SHAWN AHMED LAB - bgsa.web.unc.edu

KEITH SOCKMAN LAB

Page 123: SHAWN AHMED LAB - bgsa.web.unc.edu

Susan Lyons

Keith Sockman

Rob Aldredge

Bird song

reproduction

neuroendocrinology

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TODD VISION LAB

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Todd Vision

Evolutionary and computational genetics

Phenotypes

Phylogenies

Genetic maps

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ALAN WEAKLEY LAB

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•Alan Weakley

•Paul Gabrielson

•Carol-Ann McCormick

•Derick Poindexter

•Alexandra Permar

•Karl Fetter

UNC Herbarium

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Karl Fetter - UNC Herbarium Biogeography of Liriodendron

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HAVEN WILEY LAB

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Evolution of Signaling in Noise R. Haven Wiley

The evolution of signaling in noise requires inevitable trade-offs for both signaler and receiver. Both face diminishing returns in reducing the effects of noise.

Evolution leads to an equilibrium between receivers that make mistakes and signalers that cannot always elicit responses.

Receivers’ thresholds for response and signalers’ exaggeration of signals depend on the level of noise.

1 2

3

Wiley 2013 in press. Behaviour, Special Issue in Honor of R. H. Wiley

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CHRISTOPHER WILLETT LAB

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Poster by Christopher S. Willett Biology Department at UNC, Chapel Hill with Research support from NSF

Female with eggsac

Example of Rocky Outcrop with copepods

Tigriopus californicus- Lives in tide pool on west coast of North America

Why we study this species: •Speciation Study of divergent populations can help illuminate the process of speciation •Adaptation Can populations adapt to increasing temperatures (and how)?

Copepods-are a diverse and numerous group of crustaceans (like crabs and shrimp)

Copepod Facts:

•Abundant in fresh and saltwater

environments, in fact, likely the most

numerous animal on planet

•11,500 species, most 1-2mm some

up to 23cm

-Parasite on whales -23 cm long!

From Abaunza,Arroyo, & Reciado, Crustaceana 74(2):193-210

From Ernst Haeckel's Kunstformen der Natur

T. californicus mating pair Photo by G. Rouse

Copepods – Key Players in Aquatic Environments

Copepods in trees?

Copepods found in leaf litter in redwood forest canopy

Copepods on whales?

Larval Copepod

Aren’t copepods too small to feed whales (and fish)?

Not when there are so many of them! Sampling net for zooplankton in ocean

Photo by P. Sullivan

Sample of copepods from Bay of Fundy-food for right whales

New England Aquarium Photo

Photo by Chris Linder WHOI

Closer view of copepods from the Bering Sea

Pennella balaenopterae

Some copepods can cause disease

Some copepods can prevent disease

M. Camann, K. Lamoncha, and C. Jones, Save-the-Redwoods League, and Humboldt State University

Mesocyclops copepod eating mosquito larvae that is vector of dengue fever. Used to control dengue in Vietnam

Sea lice (a type of copepod) on salmon farms do almost ½ billion dollars of damage yearly world-wide Photo by A. Morton

Photo from ecotippingpoints.org

Page 133: SHAWN AHMED LAB - bgsa.web.unc.edu

Thiago Lima

Willett Lab

Genetics of speciation in Tigriopus californicus

I am studying genome-wide patterns of hybrid incompatibilities in populations of the copepod Tigriopus californicus. This work aims at answering 3 main questions: - What regions of the genome are contributing to

hybrid incompatibilities?

- Do the same genomic regions contribute to hybrid incompatibilities in crosses between different populations?

- How does the number of incompatibilities increase with divergence time?

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BIOLOGY TEACHING FACULTY

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Bio 101 Bio 202 Bio 252 Bio 276

UNC Biology Teaching Faculty

How do our students want to be taught?

100% Lecture 75% group work, 25% lecture Poll questions mixed into lecture Mix of polls, activities, and lecture

We asked our students early in the Spring 2013 semester about how they want to be taught – here is what over 1200 of them had to say!

Kelly Hogan

The majority of our students, from freshman to seniors, want to be taught in an active and engaging manner

Jean DeSaix

Gidi Shemer

Corey Johnson

Justin Shaffer