Mentor:  Susan Daniel

Education:

Boston University – B.S. in Biomedical Engineering, 2020

Awards and Honors:

• Dean’s List  for four semesters; Graduated Cum Laude
• Appointed Dean’s Host at Boston U.
• Selected for the Partnership for Global Health Technologies Program (Boston U.)

Research Experience:

• Sgro Lab, Boston University (Biosensors for bacterial communication)
• Karp Lab, Brigham and Women’s Hospital (Nanotechnology and cancer biology)

Current Research Activities:

The COVID-19 pandemic caused by the SARS-CoV-2 virus has led to several million deaths across the globe and coronaviruses have been listed as a top ten pandemic threat by the WHO for many years. However, much is still left to be learned about how spike sequence, membrane chemistry, and environmental conditions lead to infection caused by this virus. Specifically, the spike protein is an important target since it plays a critical role in host cell entry through membrane fusion. Mutations in the spike protein are part of the constant evolutionary process and often lead to distinctive changes in infectivity and transmission as observed with emerging mutants of the SARS CoV-2 virus. The major challenges scientists face right now are: 1) correlating spike mutation with infectivity and predicting how infectious a mutation may be, 2) predicting pandemic potential of future coronaviruses, and 3) developing broad spectrum antiviral drugs and vaccines that can work for any mutation that may emerge for SARS CoV-2. All of these challenges require a better understanding of the biological and chemical interactions between the virus and host that ultimately lead to successful infection. Such fundamental understanding will enable effective antiviral designs, identification of patterns that can be used to predict virulence, and development of diagnostics that will ensure that we are better equipped to respond to  future coronavirus pandemics. Therefore, my project is focusing on a specific region of the spike protein called the fusion peptide which has been seen to have many key conserved amino acid sequences that could prove useful in developing antiviral drugs and understanding how infection changes with changes in these important residues. In the next two years I purpose to gain insight into molecular level interactions between the fusion peptide and the host cell membrane, focusing on the role of the host’s membrane chemistry. Lipid ordering, caused by cholesterol and  saturated acyl chains, is a precursor to membrane fusion, so here I hypothesize that the presence of these components will influence ordering and alter membrane fusion. Furthermore, the amino acid sequence of the fusion peptide can also dramatically influence the interaction with the host membrane. This is because charged residues can influence the hydrophobic interactions of the fusion peptide with the membrane. Thus, I hypothesize these changes in hydrophobic interactions, due to the change in amino acid sequence, will also lead to observable changes in fusion. My project’s goals are to systematically examine each of these features to develop an understanding of the chemical rules that govern the virus entry process. By understanding these biochemical interactions and their influence on the structure and biological function of the fusion peptide and the membrane lipids, with techniques such as bulk fusion fluorescence assay, Circular Dichroism (CD) Spectroscopy, Isothermal Titration Calorimetry (ITC) and cell infectivity, I can piece together a basic science understanding of coronavirus infection and rules that govern its pathogenesis. This information would give us predictive power in determining conditions that lead to stronger interactions, more host susceptibility and greater infectivity.