The human immune system has means of detecting foreign bodies and defective cells, but some dysfunctional cells, like tumor cells, can avoid an immune response altogether. These cancer cells avoid an immune response by evading T cells (Schreiber, 2011), through the activation of the PD-1 receptor on T cells. PD-1 negatively regulates T cell activity, and this receptor is stimulated by PDL-1 and PDL-2 ligands. A new approach to cancer therapy, through immune checkpoints, can help the immune system regain an advantage over tumor cells. This experiment aims toward designing a protein--a PD-1 domain--to bind to ligands released by tumor cells. In order to produce such a therapy, however, the binding affinity of the protein must be improved. The protein's affinity will be improved with affinity maturation, with techniques such as using mutagenesis libraries and ELISA assays.

In this research project we will be developing a refined TGF-beta inhibitor by improving upon current TGF-beta antagonists. TGF-beta is a protein primarily involved in regulating cell proliferation and differentiation. TGF-beta typically stops the cell cycle at G1, preventing additional growth. It also plays a role in apoptosis. Accordingly, many cancers are often accompanied by mutations in the TGF-beta pathway. TGF-beta has also been found to play a role in atherosclerosis, marfan syndrome, and loeys-dietz syndrome. However, because we are primarily interested in inhibiting TGF-beta, we will be focusing on treating pathologies resulting from overexpression of TGF-beta. Interestingly, though TGF-beta plays a beneficial role in healthy cells by helping regulate the cell cycle, in oncogenic cells TGF-beta is often overexpressed, affecting alternate pathways. Thus, suppression of TGF-beta in cancer cells has shown promise as a targeted cancer therapy. It is also known that overexpression of TGF-beta leads to immunopathies. Recent studies have suggested that an overabundance of TGF-beta may lead to a wide range of allergic diseases in humans, given that TGF-beta supports the expansion of regulatory T cells. In finding a better antagonist for TGF-beta we aim to maximize efficiency and circulation time in the body while minimizing side effects. In doing so, we hope to help treat some of the aforementioned conditions for others in the field...Our research project will primarily be conducted using online software. First, we will investigate the nuance structure of TGF-beta and it’s receptor using online public resources, notably RCSB Protein Data Bank. RCSB Protein Data Bank will allow us to view both the chemical and three dimensional structure of molecules of interest. Moreover, it will help us characterize bonds within the proteins relevant to our research. Then, we plan on using public, open source programs such as PyMOL and RasMol to simulate docking of our antagonist. We expect this aspect of our research project to take up the most time due as we optimize the fit of our TGF-beta inhibitor...

Biofilms are complex, interdependent communities of surface-associated bacteria. The microorganisms are enclosed in an exopolysaccharide matrix that can occur on any surface, in particular aquatic and industrial water systems. Because they often form sessile communities on medical devices and food preparation settings, millions of people in the developed world are affected by diseases such as cystic fibrosis and pneumonia, with some experiencing death as a consequence. For the safety of both plants and animals, it is vital to harness the ability to eliminate biofilms. However, as bacteria switch between a planktonic lifestyle to a biofilm lifestyle, the polymers in their matrix retard diffusion of antibiotics, giving biofilms an increased tolerance to host immunological defenses, stress, and biocides. Moreover, there is a greater frequency for individual bacteria in biofilms to develop antibiotic resistance due to the higher probability of horizontal gene transfer among bacteria in close proximity. A biofilms’ resistance to antibacterial agents warrants the need to either prevent initial growth, sterilize the colony, or inhibit communication. In our study, we seek to focus on the latter of the three.