Selective effects on sperm functions
by novel compounds

 

Professors Robert Flowers (Chemistry) and Barry Bean (Biological Sciences)

Team Leaders:

Barry Bean, Ph.D.
Robert Flowers, Ph.D.

Graduate Students:

Rajni Singh
Jennifer Venditti

Undergraduate Students:

Jessica Adler
Emily Hoffman
Melanie Rudnick
Kevin Turezyn

 

Commonly used spermicides like nonoxynol-9 have some undesirable side effects and detrimental consequences for some infectious processes.  As a result, improved and alternative spermicides are needed.  We are synthesizing and testing novel chemical compounds; these may weaken sperm cells and microbes.   The architecture of human sperm cells includes several distinctive membrane regions that undergo substantial changes during the life history of the sperm cell.  Specific changes must take place within the compartments and membranous surfaces of sperm to make them able to fertilize an egg.  We will examine effects of a number of novel compounds on the functions of human sperm.  Outcomes may lead to new strategies for contraception, or improvements in prevention of disease and pregnancy.

Modeling local synaptic control
in neural coincidence detectors

 

Professors Linghai Zhang (Mathematics) and R. Michael Burger (Biological Sciences)

Team Leaders:

R. Michael Burger, Ph.D.
Linghai Zhang, Ph.D.

Graduate Students:

Matt Fischl
Akongnwi Clement Mformbele

Undergraduate Students:

T. Dalton Combs
Amber Horner
Adam Kasper
Joseph Sette
Victoria Stuss

 

 

Sensory neurons often process information over a large range of a given stimulus parameter. For example, the auditory system can function over a range of sound intensities corresponding to a 10¹³ fold increase in sound pressure from detection threshold. Indeed, special mechanisms at several levels of the auditory system are in place to maintain low detection thresholds but prevent saturation (overload) of the system. We are exploring one such mechanism at a synaptic site that requires very precisely timed synaptic input to achieve its computation function. Specifically, we propose that a particular receptor system (the GABA_B receptor) locally controls the strength of excitatory and inhibitory inputs to this neuron type. Further, we expect that local control of synaptic strength maintains the circuit in an optimal operating range. We will use mathematical modeling techniques to independently manipulate each target of the GABA_B R activation and inject our modeled synaptic currents back into the cells. Our approach will combine computational modeling with empirical hypothesis testing to determine the impact of these receptors on circuit function.

Analysis of Intracellular Mechanics

 

Professors Linda Lowe-Krentz (Biological Sciences), Daniel Ou-Yang (Physics), and Samir Ghadiali (Mechanical Engineering & Mechanics)

Team Leaders:

Linda Lowe-Krentz, Ph.D.
Daniel Ou-Yang, Ph.D.
Samir Ghadiali, Ph.D.

Graduate Students:

Hannah Dailey
Angela Lengel
Meron Mengistu

Undergraduate Students:

Hannah Brotzman
Theon Francis
Jeremy Olen
Jeff Park
Laura Ricles

 

Biologists have made great strides in understanding organism function at the cellular and molecular level. However, we know very little about how physical and/or biomechanical forces alter cell function. The goal of this study is to determine how different biomechanical forces alter the mechanical and structural properties of cells. We will focus on endothelial cells which line blood vessel walls and experience a variety of flow-induced forces.  We hypothesize that these forces will alter the cell’s cytoskeletal structure and mechanical properties. Cultured endothelial cells will be exposed to various flow conditions, optical techniques will be used to monitor changes in cytoskeletal structure and cell mechanics and computational models will be used to analyze experimental results. We hypothesize that global forces like laminar flow and chemical stresses will result in ordered increases in the actin cytoskeletal network, while localized forces will cause increased, but structurally different actin cytoskeletal changes. Knowledge of how biomechanical forces influence cell function may lead to a better understanding of the different disease conditions that are characterized by cellular dysfunction (i.e. atherosclerosis).

front: Samir Ghadiali, Linda Lowe-Krentz and Daniel Ou-Yang back: Hannah Dailey, Angela Lengel, Theon Francis, Jeff Park, Meron Mengistu, Laura Ricles

Integrating computational and experimental methods in the analysis of molecular complexity in nature

 

Professors Daniel Lopresti (Computer Science & Engineering), Ian Laurenzi (Chemical Engineering), and Stefan Maas (Biological Sciences)

 

Team Leaders:

Stefan Maas, Ph.D.
Ian Laurenzi, Ph.D.
Daniel Lopresti, Ph.D.

Graduate Students:

Dylan Dupuis
Mark Strohmaier

Undergraduate Students:

Benjamin Evans
Jessica Latona
Allison Porman
Patricia Rekawek

 

The delineation of whole genome sequences including the human genome have opened up new avenues to study biological phenomena using combined computational and experimental methods. Novel, fundamental questions about diversity and complexity in nature have also arisen from the obtained genomic information. For example, the tremendous complexity of higher organisms, in particular humans, cannot be explained by the number of genetic building blocks present in genomes when comparing primitive species, such as worms and flies, to mammals and primates.

Our team will be applying our extensive experience in computational biology as well as the molecular biology of RNA editing, which represents a phenomenon that allows organisms to produce many more functional molecules than what would be predicted from analyzing the genome.

We are working to develop a new software platform that will allow us to mine sequence databases to uncover genes that are subject to modification by RNA editing. The computational work is closely linked to experimental work using mammalian specimen to validate candidate targets and to address how editing affects individual gene function.

front: Patricia Rekawek, Jessica Latona, Allison Porman, Benjamin Evans center: Mark Strohmaier, Dylan Dupuis back: Ian Laurenzi, Stefan Maas, and Daniel Lopresti