|Friday, April 20th|
Carra Lyons, Winthrop University
Iron is essential to the survival of nearly all known organisms. Free iron in the cell also acts as a catalyst, reacting with common oxygen species within the cell, creating hydrogen peroxide and hydroxyl radicals. Every organism has to have a way to control iron uptake, to inhibit excess levels of iron within the cell. In S. pneumonia, the iron uptake mechanism is activated by extracellular iron; however, the sensory mechanism used to inhibit this uptake is not yet well understood. When iron is sensed extracellularly, a complex known as Stk-P is activated, and in the presence of ATP, this molecule will phosphorylate RitR. When not phosphorylated, RitR is bound tightly to the DNA of S. pneumonia in close proximity to the piu (pneumococcal iron uptake operon), preventing transcription of that portion of the DNA. When phosphorylated, RitR is not bound to the DNA, allowing transcription to occur. This research focuses on the location of phosphorylation on RitR. This will help understand how this protein functions and how it interacts with the DNA. Additionally, this work explores the difference in binding between RitR in its purified form, and the modified version of RitR. The phosphorylation sites on RitR were identified, and the structure changes caused by this phosphorylation were also explored. The sites that are modified by the kinase were identified to be Ser-19, Tyr-163, Thr-168, and Ser-172. Based on a homology model, three of these sites are located on a single helix in the DNA binding domain, while the Ser-19 site is located on the opposite side of the protein. The effects of these sites and their modification on the function of the protein will be explored further by modifying these amino acids to prevent the kinase from phosphorylating at these positions. The effects will then be observed on DNA binding to determine how this would influence the protein as it interacts with the piu.
Autumn S. Leggins, Winthrop University
Oct4 is a transcription factor that is crucial for the induction and retention of pluripotency in pluripotent stem cells. The potential for Oct4 to regulate the developmental potency of multipotent stem cells like adipose-derived mesenchymal stem cells (ADSCs) is not well understood. One approach to explore Oct4’s role would be through the use of cellular assays to control the expression of Oct4. This can possibly be accomplished by introducing a biological switch and the gene of interest into ADSCs. In this project, the GeneSwitch™ System was used to ultimately induce Oct4 expression. Oct4 was extracted from a pEX-K4-Oct4 plasmid (from Eurofins Genomics) that contained the gene of interest and was inserted into one of the GeneSwitch™ System plasmids that have the same recognition sites as those used to remove Oct4 from the pEX-K4-Oct4 plasmid. The newly combined GeneSwitch™ plasmid with Oct4 can then be placed into ADSCs along with the plasmid that will act as a biological switch. With this system put into ADSCs, it is expected that Oct4 levels will be successfully controlled. Once controlled, investigations can be completed to determine how Oct4 expression levels influence the developmental potency of ADSCs. Gaining the ability to control Oct4 will also open up the opportunity to test other hypotheses, including determining how Oct4 expression levels influence the developmental potency of other cell types. This knowledge could then be applied to tissue engineering and regenerative medicine strategies that rely upon the ability of ADSCs to produce specified cell lineages.
Brittney Ramsey, Winthrop University
Faculty Mentor: Ginger Williams, Ph.D.
Skin cancer is the most common cancer facing today’s society. Between 1982 and 2011, the percentage of Americans who developed melanoma doubled; one in five Americans will develop skin cancer within their lifetime. If preventative measures are not taken, 112,000 new melanoma cases are expected in the year 2030 alone. One method of combating the rising incidence numbers is through creating an educational program to combat the lack of proper skin care and skin protection knowledge. From previous literature, it is clear that young adults are a key demographic to consider when creating an interventional educational program, but results using this method have been modest, and it is unknown if the behavioral changes are continual. A customized education program is to be presented to students, who will be given a survey to assess their base knowledge, knowledge after the presentation, and retained knowledge after a few months. This study seeks to determine if an educational program would be an efficient method of combating the numbers at Winthrop University, gaining information as to the effectiveness and long-term effects of intervention programs within college-age individuals.
Maryssa Shanteau-Jackson, Winthrop University
Faculty Mentor: Takita Sumter, Ph.D.
Chemoresistance is a major limitation to effective cancer treatment regimens. Specifically, cancer stem cells, self-renewing cells that can differentiate, provide a pathway to escape treatments by targeting rapid cell division pathways. High mobility group A1 (hmga1) is implicated in the initiation and progression of various cancers and may be involved in the genetic events leading to the growth of cancer stem cells. Mice bearing the (hmga1 transgene develop aggressive lymphoid malignancies and are less responsive to chemotherapies that have been tested. To this end, we explored the role of (hmga1 in chemoresistance using 5-fluorodeoxyuridine (5-FdUrd). 5-FdUrd is the active antimetabolite of a mainstay in cancer treatment whose activity is based on the misincorporation of fluoropyrimidines into DNA and RNA during their synthesis. Studies were conducted using HCT-116 colorectal cancer cells with high endogenous levels of hmga1 proteins. These cells were treated with varying concentrations of 5-FdUrd and IC50 values were determined to be comparable to, but slightly higher than, previously published values. Silencing of (hmga1 expression by siRNA duplexes targeting different genetic regions enhanced sensitivity to 5-FdUrd by greater than 1.5- to 3-fold when compared to native HCT-116 cells. Collectively, we provide data that support the role of (hmga1 in orchestrating the ability of cancer cells to evade the impacts of chemotherapy, particularly those targeting cell division pathways. We expect that this work will contribute to an expanded understanding of cancer initiation and progression and will facilitate development of more effective cancer therapies.
Colin Frazier, Winthrop University
In this paper, we analyze a system of six ordinary differential equations to model dynamics of the human papilloma virus (HPV), cells infected with the virus, cells susceptible to the virus, precancerous cells, cancerous cells, and the immune system's response. The model considers the dynamics of these cell populations when the immune system is boosted through immunotherapy treatment. We find sufficient global stability conditions using the method of localization of compact invariant sets. Graphs of numerical simulations show the dynamics of the system when conditions are met and when conditions are not met.
John Brotemarkle, Winthrop University
Faculty Mentor: Kristen Abernathy, Ph.D., and Zachary Abernathy, Ph.D
Drug resistance, also known as multidrug resistance (MDR), is the leading cause of chemotherapy failure in treating cancer. This drug resistance in cancer cells can be transferred from resistant cancer cells to sensitive cancer cells. Sensitive cancer cells can become resistant through three main methods: via direct cell-to-cell contact with resistant cancer cells, through a membrane, or through exposure to the treatment drug. In our project, we take into account the transfer of drug resistance from resistant to sensitive cancer cells via direct cell-to-cell contact. We then introduce an immune response and chemotherapy, and establish conditions on treatment parameters in the resulting system to ensure a globally stable cure state. We conclude with evidence of a limit cycle and conjecture the existence of a Hopf bifurcation.
WEST 219 Session II, 2:45-4:15 p.m.