Dec 9, 2020
Professor William Gelbart
In a new video, UCLA physical virologist Professor William Gelbart discusses the therapeutic and preventative COVID-19 vaccine that his group is developing. 
 
A Distinguished Professor of Chemistry & Biochemistry, Gelbart was one of three faculty members sharing overviews on a variety of research projects pertaining to the COVID-19 pandemic at the May 29th UCLA Division of Physical Sciences webinar titled “The Science of Our Lives: Research That Matters During a Pandemic”.
 
 
The panel was moderated by Physical Sciences Dean Miguel García-Garibay with the opportunity for viewers to submit questions for the experts to address. In addition to Gelbart, the panelists included Professor Rick Schoenberg, Statistics, discussing developments in the statistical modeling of infectious diseases, especially models helping to forecast the spread of COVID-19; and Professor Suzanne Paulson, Atmospheric & Oceanic Sciences, discussing air pollution and air quality in L.A. during the pandemic, in particular how aerosol particles and droplets move in the environment, and how masks and filters work.
 
In Gelbart’s presentation he described an approach to viral vaccines that involves delivery of the vaccine in the form of messenger RNA (mRNA), much like the Pfizer and Moderna vaccines that are becoming available on a large scale within the next several months. But unlike these latter vaccines, the RNA is protected and delivered in a unique particle that is synthesized in a test tube, from purified RNA – coding for COVID-19 spike protein – and a very special protein, exactly 180 copies of which self-organize into a perfectly symmetric, one-molecule-thick, shell (capsid). Also, the RNA has been genetically engineered to be self-replicating, so that many copies of it are made before it is translated into spike protein in the antigen-presenting immune cells to which the capsid has been targeted. These mRNA-containing capsids – “T-particles” – are designed to elicit a strong response to the virus from killer T cells. An accompanying B-cell response, involving the synthesis of neutralizing antibodies, is elicited separately by conjugating another set of capsids (“B-particles”) to a regular array of intact spike proteins. In collaboration with the group of Professor Otto Yang, M.D., in the School of Medicine, the Gelbart group is currently beginning in vitro testing of the activation of killer T cells by antigen-presenting cells that have been incubated with the vaccine particles.   
 
Gelbart joined the UCLA Chemistry & Biochemistry faculty in 1975, when he switched from photochemistry and molecular spectroscopy theory to the statistical mechanics of liquid crystals, self-assembling systems, polymer solutions, colloidal suspensions, and thin films.  During a 1998-1999 sabbatical year at the Institute for Theoretical Physics in UC Santa Barbara and at the Curie Institute in Paris, Gelbart became deeply intrigued by viruses and over the course of the next several years, with his UCLA colleague Professor Charles Knobler, established a laboratory to investigate simple viruses outside their hosts and isolated in test tubes. Early results included: the first measurement of pressure inside DNA viruses, establishing that it is as high as tens of atmospheres depending on genome length and ambient salt concentrations; and the demonstration that capsid proteins from certain viruses are capable of packaging a broad range of lengths of heterologous RNA with 100% efficiency. This work, along with that of several other groups in the United States and Europe, helped launch the field of "physical virology". Most recently he moved his viruses from test tubes to host cells, and from wildtype viruses to artificial viruses and virus-like particles, engineered for purposes of delivering self-replicating RNA genes, RNA vaccines, and therapeutic microRNA to targeted mammalian cells.
 
 
Penny Jennings, UCLA Department of Chemistry & Biochemistry, penny@chem.ucla.edu.