The proposed studies will detail the role of microRNAs as critical regulators of genes expressed in the Schwann cell lineage, and thus will have important implications for understanding the pathomechanisms of various peripheral neuropathies including Charcot-Marie-Tooth disease.

James R. Bartles, PhD
Professor of Cell and Molecular Biology
Project title: The Roles of Espins in Hair Cell Stereocilia
Sponsor: National Institute on Deafness and Other Communication Disorders

Hearing and vestibular function depend critically on fingerlike protrusions called stereocilia, which are found atop hair cells in the inner ear. At the core of each stereocilium is a specialized cytoskeletal element, a parallel actin bundle, which acts as a molecular scaffold and determines stereocilium dimensions, placement, and physical properties. We have discovered and are characterizing a novel family of actin-bundling proteins, the espins, which cross-link the stereocilium's parallel actin bundle and thereby regulate stereocilium length, diameter, and integrity.

In addition, we have found that espins are the target of genetic mutations that cause deafness and vestibular dysfunction in mice and in humans. The goals of this grant are to determine how espins with deafness mutations differ from normal espins in their interactions with actin filaments and bundles, to elucidate the effects of espin deafness mutations on hair cell stereocilia in mouse models, and to use a newly developed epithelial cell model to study the targeting and interactions of espins and other stereocilium proteins.

Julius P. A. Dewald, PhD
Associate professor and chair, Department of Physical Therapy & Human Movement Sciences
Project Title: The Loss of Independent Joint Control of the Upper Limb in Spastic Hemiparetic CP
Sponsor: National Institute of Neurological Disorders and Stroke

Movement discoordination in individuals with spastic hemiparetic cerebral palsy (SH-CP) may be caused by stereotypic multi-joint movement patterns (synergies), reflecting a loss of independent joint control. Using virtual mechanical environments generated by a 3D robot, we plan to quantify the presence and extent to which this discoordination exists. Finally we propose to quantify differences in morphology between brain hemispheres and fiber density in these individuals versus control subjects and its relationship with the expected loss of independent joint control.

Rick McGee, PhD
Associate professor of medical education and faculty development
Project Title: Career Decision Making of Future Minority Biomedical Science Faculty
Sponsor: National Institute of General Medical Sciences

The study is designed to help us understand how students in the life sciences, especially those from underrepresented groups, view and make decisions about their future careers. Of particular interest to us is how students make decisions about academic careers as one option for young scientists. Although much research has been done on the factors that influence college student retention in the sciences in general, almost nothing is known about how those who actually enter PhD programs decide what to do with their PhD training. The multi-year study will use annual semi-structured interviews to follow the career thinking and planning of more than 250 students from across the U.S., beginning as juniors in college and continuing through their first years of PhD training or other postbaccalaureate activities. Qualitative research methods will be used to study the patterns and primary influences on student thinking and intentions across this diverse sample of future scientists.

Amy S. Paller, MD
Walter J. Hamlin Professor of Dermatology
Chair, Department of Dermatology
Project title: Genetics of Atopic Dermatitis-Eczema Herpeticum
Sponsor: National Institutes of Health

This grant is for two studies as part of the Atopic Dermatitis Vaccinia and Immunization Network (ADVN). The two titles are: 1) Genetics of Atopic Dermatitis-Eczema Herpeticum 2) ADVN Biomarker Registry Study. The objective of the genetics study is to use new genomic technologies using high-throughput genotyping and guided by gene expression profiling studies in skin samples infected with three different viruses (HSV-1, Vaccinia and molluscum contagiosum virus [MCV]) to provide significant and novel information on the pathways responsible for the development of Eczema Herpeticum and possibly other relevant viral infections seen more commonly in AD subjects. 
 
The purpose of the registry study is to facilitate ADVN clinical research designed to reduce the risk of eczema vaccinatum (EV), a complication of vaccinia immunization that occurs in patients with atopic dermatitis, by collecting the relevant data and blood samples and providing participating investigators with access to a pool of potential study subjects for subsequent studies.

This project will fund high-resolution imaging studies of the synaptic circuit organization of the motor area of the cerebral cortex. By identifying and quantitatively characterizing the basic circuits in motor cortex, we hope to shed light not only on synaptic mechanisms underlying the cortical control of movement, but also provide a framework for identifying pathological mechanisms at the circuit level involved in movement disorders, paralysis, and other neurological diseases involving impairment of voluntary movement.

MHC class Ib molecules comprise the majority of the MHC class I family. However, much less is known of their role in immunity compared to classical MHC class Ia molecules. The goals of this project are to investigate the effect of thymic-selecting pathways on the in vivo function of MHC class Ib-restricted CD8+ T cells and to examine the relative role of various MHC class Ib-restricted CD8+ T cells in host defense against intracellular bacterial infection. Studies on this relatively uncharacterized segment of the mammalian immunologic repertoire may lead to improved methods for vaccination against infectious diseases.

The goal of this research is to define the interactions between the prefrontal cortex and interconnected thalamic nuclei in mediating acquisition and consolidation of trace eyeblink conditioning, a well-studied paradigm for associative learning and memory in mammals. Reversible inactivation of the prefrontal cortex will be used to define sites required for expressing conditioned responses. Connections of these sites with the thalamus will be identified by neuroanatomical tracing. The relative activities of these interconnected sites will be determined by recording behavioral responses and responses of multiple single neurons from each site in vivo. The experiments should lead to a better understanding of the role of the forebrain in associative learning, age-related learning and memory impairments, and the neural mechanisms mediating addiction.