Doctor of Philosophy (PhD)
First Advisor's Name
Bernard S Gerstman
First Advisor's Committee Title
Second Advisor's Name
Prem P Chapagain
Second Advisor's Committee Title
Third Advisor's Name
Third Advisor's Committee Title
Fourth Advisor's Name
Fourth Advisor's Committee Title
biological and chemical physics
Date of Defense
Viruses do not possess complete cellular machinery but have the ability to reproduce by utilizing cellular machinery inside host cells. They are nanoscale machines that rapidly modify (evolve) their molecular components to cause disease and death. Therefore, emergence of deadly infectious viruses is a monumental health concern and understanding how viruses are able to enter, replicate, assemble and egress from the host cell is important to mitigate the threat.
A fully active, infectious viral structure is known as a virion. A virion contains genetic material and is enclosed by a capsid. The capsid is a protein shell and some viruses also are coated by a lipid membrane. My research focuses on viral proteins that interact with lipid membranes in host cells. The lipid molecules can be part of the cellular membrane or part of lipid structures within a cell, such as the endoplasmic reticulum. In my research, I used molecular dynamics computational techniques to study the interactions of the filovirus matrix protein, also known as VP40, of Ebola and Marburg viruses with the lipid molecules in the human plasma membrane. VP40 proteins associate in the inner layer of the plasma membrane and oligomerize to form the matrix that gives the shape of the virion particle. My research focuses on the membrane association, membrane transportation of VP40, which represents the early stage of the virus’ assembly inside the cell. I have identified the amino acids playing important roles in both membrane association and conformational flexibility. I also investigated the Zika virus NS1 protein association on the outer layer of endoplasmic reticulum, which is where the Zika virus forms the virion. The aim of my research is to use molecular level understanding of the virus life-cycle to develop improved molecular interventions such as designing drug molecules that disrupt the functions of the VP40 and NS1 proteins, for prevention and cure of viral diseases.
Previously Published In
Bhattarai, N.; Gc, J. B.; Gerstman, B. S.; Stahelin, R. V.; Chapagain, P. P. Plasma membrane association facilitates conformational changes in the Marburg virus protein VP40 dimer. RSC Adv 2017, 7 (37), 22741-22748.
Pavadai, E.; Bhattarai, N.; Baral, P.; Stahelin, R. V.; Chapagain, P. P.; Gerstman, B. S. Conformational Flexibility of the Protein-Protein Interfaces of the Ebola Virus VP40 Structural Matrix Filament. J Phys Chem B 2019, 123 (43), 9045-9053.
Wijesinghe, K. J.; Urata, S.; Bhattarai, N.; Kooijman, E. E.; Gerstman, B. S.;Chapagain, P. P.; Li, S.; Stahelin, R. V. Detection of Lipid Induced Structural Changesof the Marburg Virus Matrix Protein VP40 Using Hydrogen/Deuterium Exchange MassSpectrometry. The Journal of biological chemistry 2017.
Bhattarai, Nisha, "Structural Dynamics of Membrane Interacting Viral Proteins" (2021). FIU Electronic Theses and Dissertations. 4795.
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