Biological Sciences Funding Program 2013-2014 Awardees

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The Office of the Vice President for Research at the University of Iowa is proud to present the 2013-2014 recipients of the Biological Sciences Funding Program (BSFP).  The awards are designed to support seed funding to develop pilot data and to conduct preliminary work that will enable UI researchers to submit competitive applications for external research grants.

 

Gail BishopGail Bishop, Professor, Microbiology
Role of CD40 in preventing Obesity and insulin resistance

We recently discovered that CD40, an immune receptor essential for immune responses, plays an important role in the progression of obesity and insulin resistance. CD40-deficient mice exhibited an unexpected tendency for obesity and insulin resistance. Defining the means by which CD40 regulates obesity could lead to novel therapeutic approaches for controlling metabolic diseases. This project thus explores possible mechanisms and will allow us to obtain preliminary data necessary for obtaining external funding from the NIH, the American Diabetes Association, or other sources.
 

Alan KayAlan Kay, Professor, Biology
The mechanism of sensory transduction in the auditory system of Drosophila melanogaster

Identification of the primary transduction mechanisms at work in sensory cells is essential for comprehending how sensory systems work.  Our primary objective in this proposal is to identify the nature of the ion channels involved in mechanotransduction in fly's ears, Johnston's organ (JO), by intracellular recording from its component cells. We will investigate (a) the channels activated by mechanical stimulation (b) the ionic conditions in the scolopale space which surrounds the sensory dendrite and (c) the mechanical properties of JO.
 

Maurine NeimanMaurine Neiman, Assistant Professor, Biology
Developing a new multicellular animal model for aneuploidy

Human cells and bodies are severely comprised when just one of the full complement of 44 autosomes are missing. This phenomenon, aneuploidy, is lethal or generates profound developmental abnormalities  when it occurs at the zygote stage, characterizes most tumors, and may play a central role in cancer. Despite its severe consequences, aneuploidy occurs so often in humans that it is implicated as the leading cause of miscarriage, developmental disabilities, and mental retardation. A comprehensive understanding of the causes and consequences of aneuploidy has been limited by the lack of availability of model systems featuring naturally occurring viable and heritable aneuploids; rather, aneuploids must be created via artificial means. Here, I propose to leverage my recent discovery of likely widespread naturally-produced aneuploidy in a freshwater snail (Potamopyrgus antipodarum) to document and quantify the range and types of heritable aneuploidy in P. antipodarum and begin to elucidate the mechanism(s) by which these snails produce aneuploid eggs. These projects will comprise necessary steps towards transforming Potamopyrgus antipodarum, a freshwater snail already emerging as a model system for the genomic consequences of sexual reproduction and polyploidy, into a model system ideally suited to study aneuploidy.
 

Ibrahim Tarik OzbolatIbrahim Tarik Ozbolat, Assistant Professor, Industrial Engineering
Micro-fluidic Channels as Vascular Scaffolds for Direct 3D Organ Printing

The long-term goal of the PI is to bioprint a 3D artificial pancreas that is glucose sensitive. Our approach to achieve this goal is by exploiting pluripotent stem cell derived insulin producing cells (iPCs) and assembling them into a 3D artificial organ. In order to achieve this goal, this project particularly aims at printing and integrating blood vessel-like micro-fluidic channels to serve as a vascular system for 3D pancreatic organ fabrication. The outcome of this research has the potential to improve the development in biotechnology and reduce the demand for organ transplantation drastically. Our hypothesis is that printed vessel-like micro-fluidic channels will support viability of iPCs and formation of pancreatic organs in 3D.

Laura Ponto, Associate Professor, Radiology
Brain pH and Alzheimer's Disease

Alzheimers disease (AD) will pose a significant medical and financial burden to the US over the next several decades as the population ages.  Common to the models characterizing the events leading to the development of AD, is the key role of acidosis. However, no one has yet assessed brain pH changes associated with AD. This project will characterize the cerebral microenvironment with PET and MR imaging measures sensitive to pH and cellular metabolism (e.g., glucose, lactate) across the spectrum of cognitive function (healthy controls (HC), mild cognitive impairment (MCI) and AD) and amyloid (the hallmark pathology of AD) burden in order to investigate the potential role of pH as a mechanistic link underlying the AD pathological cascade.

 

Stefan StrackStefan Strack, Professor, Pharmacology
Mitochondrial dynamics in pain

Mounting evidence indicates that mitochondrial function is determined by mitochondrial morphology, which in turn depends on the balance of fission and fusion reactions. Elongated mitochondria can sustain higher rates of respiration and sequester Ca2+ more effectively, while shorter mitochondria are more effectively transported to distant synapses in neurons, thus promoting both synapse development and function. In preliminary studies, we found that knockout of a neuron-specific mitochondrial shape regulator has profound consequences for neuronal development and function. Mice that lack Bb2, an outer mitochondrion-targeted regulatory subunit of the protein Ser/Thr phosphatase PP2A show hyperphosphorylation and inactivation of the mitochondrial fission enzyme dynamin-related protein 1 (Drp1) and consequent elongation of neuronal mitochondria by unopposed fusion. This results in CNS wiring defects, blunted synaptic plasticity, and impaired memory performance, but also resistance to focal ischemic stroke. These CNS phenotypes are accompanied by equally intriguing PNS phenotypes, which are the subject of the present proposal. We found that heterozygous and homozygous Bb2 deletion lowers the pain threshold in response to heat and touch (thermal and mechanical hyperalgesia). In addition, Bb2 mRNA levels are dramatically downregulated in a model of neuropathic pain. We plan to explore these clinically significant findings by further characterizing the pro-nociceptive phenotype in Bb2 KO mice in models of acute, subacute (inflammatory), and chronic (neuropathic) pain (Aim 1), and pursue cutaneous pain fiber sprouting as a possible mechanism (Aim 2).  Results from this project will increase our understanding of the role of mitochondria in pain transmission, but may also lead to new treatments for insensate and painful neuropathies and other chronic pain conditions.
 

Bruce TomblinBruce Tomblin, Professor, Communication Sciences Disorders
Corticostriatal Structural and Functional Connectivity in Adults with Specific Language Impairment

The principal aim of the proposed project is to perform analyses of structural and functional neural connectivity in individuals with and without specific language impairment (SLI). We have hypothesized that the corticostriatal system, at least in part, accounts for the language learning difficulties in SLI. A recent structural imaging study we conducted provided strong evidence of subcortical abnormalities associated with individual differences in language. The imaging data from study allows for diffusion tensor tractography analysis and resting-state functional magnetic resonance imaging analysis that have not been performed. In the proposed project, we will examine the corticostriatal structural and functional connectivity in individuals with SLI in contrast with a control group.
 
Michelle VossMichelle Voss, Assistant Professor, Psychology
Sparking the plastic brain: Effects of aerobic exercise on brain function
 
Aerobic exercise is one of the few non-pharmacological interventions that has consistently demonstrated broad benefits for the aging mind and brain. However, little evidence exists about the neurobiological mechanisms underlying these benefits in humans, and the time and cost of large-scale randomized controlled exercise trials slows the rate of discovery. The objective of the proposed project is to determine the effects of an acute bout of aerobic exercise on clinically relevant brain networks and memory performance in healthy elderly, which could accelerate systematic examination of the optimal exercise dose to maximize brain health and quality of life.