INBRE 3 (2015-2020) introduced the Developmental Research
Project (DRP) program that allows individual faculty at SC INBRE network
institutions to submit competitive proposals for biomedical research. Of nine
DRP awards conveyed statewide to PUIs in 2015, two were received by Furman
faculty (Prof. Jason Rawlings and Prof. Renee Chosed). In 2016, Prof Alison
Roark received this award. Each of these researchers will receive over
$75K/year in research support. A brief overview of their research focus is
mechanisms of chromatin decondensation in lymphocytes by Dr. Jason Rawlings
Control of T cell proliferation is essential to proper immune function; lack of proper control can lead to pathologies such as autoimmunity, immunodeficiency, and cancer. STAT5 is a transcription factor that is absolutely essential for peripheral T cell proliferation. Following T cell receptor (TCR) engagement, activated T cells produce IL-2 which induces proliferation via STAT5. Naïve T cells, for which TCR engagement has not occurred, are refractory to IL-2 stimulation, remaining quiescent during an immune response. This ensures a clonal expansion of antigen specific T cells. Recently, we demonstrated that IL-2 induces STAT5 activation and nuclear localization in naïve T cells; however, STAT5 cannot engage DNA due to the condensed nature of chromatin in these cells. This condensation is not due to global modification of histones as previously thought, but to a higher-order chromatin condensation that is dependent on the activity of the condensin II complex. In this proposal we will determine the signaling pathway(s) downstream of the TCR that are responsible for chromatin decondensation during T cell activation. We will also determine if chromatin condensation is a conserved mechanism to regulate proliferation in other lymphocyte populations. These studies will provide important insight into the epigenetic control of lymphocyte proliferation and function.
INTERSPECIFIC COMMUNICATION BETWEEN ANEMONES AND THEIR AGAL SYMBIONTS BY DR. ALISON ROARK
evolutionarily ancient animals including jellyfish, anemones, and corals, many
of which form symbioses with intracellular, photosynthetic algae in the genus Symbiodinium.
The goal of the proposed project is to determine the extent to which and the
mechanism by which algal symbionts regulate development and reproduction of
their cnidarian hosts. My hypothesis is that algal symbionts produce compounds
that directly modulate host performance. Given their evolutionarily ancient
origins, simple body plans, well established life histories, and mutualistic
interactions with photosymbionts, cnidarians are particularly appropriate
models for studying the impacts of interspecific cell signaling processes. In
particular, studying the effects of exogenous compounds on reproductive
function of anthozoans can provide information about conserved signaling
pathways that are relevant to all animals. Phytochemicals such as flavonoids
are increasingly recognized as endocrine-active compounds that influence
reproductive capacity of animals including humans. My proposed work using the
sea anemone Aiptasia pallida thus provides insight into the effects of
plant-derived compounds on reproductive performance and the mechanisms
underlying these effects in all animals, not just cnidarians.
REGULATION OF POSTTRANSLATIONAL MODIFICATIONS IN HUMAN DISEASES BY DR. RENEE CHOSED
The overall research goal is to understand the role that posttranslational modifications play in disease progression. Posttranslational modifications function to regulate a variety of events in the cell including signal transduction, protein targeting, degradation, enzymatic activity and protein-protein interactions. Misregulation of posttranslational modifications often occurs due to mutations in the enzymes that add and remove these modifications from target proteins. For example, posttranslational modifications to histones impart epigenetic regulation upon the human genome, which help determine whether genes are actively transcribed or repressed. The histone modifying enzymes that add and remove these modifications have been implicated in various cancers and other human diseases. Due to their importance in controlling gene expression, these modifying enzymes have been utilized as drug targets in cancer therapies (Arrowsmith et al., 2012). Further complicating the scheme, the histone modifying enzymes themselves are highly regulated, thus having a clear understanding of how these enzymes are controlled is essential in identifying and developing new targeted therapies.