Research
We have 3 project areas investigating the biophysical chemistry of viral infection and lipid membranes
Project 1: Experimental Studies of Sendai virus
Sendai virus is the prototypical member of the paramyxoviruses, a family of viruses which includes the human parainfluenza viruses, mumps, measles, and other important human and animal viruses. Sendai is also a common viral vector, and has been developed for use in gene therapy and vaccine development, among other uses. In this project, we are investigating the early stages of Sendai virus infection (binding and fusion) using sensitive fluorescence microscopy techniques, which allow us to study individual viruses. We observe the individual viruses binding and fusing with host cell membrane mimics called model lipid membranes, which we construct inside microfluidic devices. This allows us to simplify the complex host cell environment, enabling us to ask direct biophysical questions about key molecular interactions.
Project 2: Computational Modeling of Flavivirus Fusion
Flaviviruses are RNA viruses that include well-known human pathogens such as Zika virus, West Nile virus, and Dengue virus. Unlike paramyxoviruses, which are primarily transmitted via respiratory routes, flaviviruses are typically transmitted between humans by vectors (mosquitoes, ticks, etc.). However, as is true for paramyxoviruses, membrane fusion is a required feature of flavivirus infection of host cells. For flaviviruses, fusion is mediated by the viral E protein, which undergoes a series of structural rearrangements to bring the host membrane into close proximity with the viral membrane, much like a grappling hook being shot out by the virus into the host membrane. This fusion mechanism for flaviviruses is an ongoing area of research. Some data sets have identified key intermediates in the process, but many steps and features remain unclear. In this project area, we are modeling flavivirus fusion using computational techniques in order to gain insight into the molecular fusion mechanism.
Project 3: Bio-analytical Studies of Model Lipid Membranes
Cell membranes are very complex - containing many different classes and types of lipid molecules. Model lipid membranes are membranes prepared artificially in the lab using a small number of purified lipids, and they afford the experimenter incredible control over membrane composition in a way not possible in the complex cellular environment to ask specific questions. They can be prepared in a range of different sizes and geometries – such as liposomes (small spherical membranes), and glass supported bilayers (planar membranes on a glass surface). While model lipid membranes are used quite widely in fields ranging from basic science (as in our lab) to drug delivery and drug formulation, the influence of the preparation methodology on the composition of these membranes is often not carefully studied. In this project area, we are studying that question by developing and applying analytical methods to quantify the lipid composition of model membranes. We anticipate that our data will be of widespread interest to researchers in many fields – including basic research, drug delivery and formulation, and biotechnology – with an interest in improved preparation of model membranes.