About

William M. Gelbart is a Distinguished Professor at UCLA with a background in biophysics and chemical biology. He earned his B.S. from Harvard University in 1967 and his Ph.D. from the University of Chicago in 1970. His research interests encompass statistical mechanics, focusing on structure and phase transitions in complex fluids such as liquid crystals, amphiphilic molecules, polymer solutions, and colloidal suspensions. Around 20 years ago, he shifted his focus to the study of viruses, aiming to understand their mechanisms of work. Collaborating with Avi Ben-Shaul, he contributed to theory predicting high pressures in DNA viruses and explored various aspects of RNA virus self-assembly. He established a laboratory with Chuck Knobler to perform experiments on physical aspects of viruses, including the first measurement of pressure (~50 atm) in a DNA virus and structural determinations of RNA viral genomes in their native state using advanced techniques like synchrotron small-angle X-ray scattering, fluorescence correlation spectroscopy, and cryo-electron microscopy. Over the past decade, his research has expanded to include plant, insect, and mammalian viruses, moving from in vitro studies to investigating how these viruses operate within host cells. His work also involves collaborations with pharmaceutical and biotech companies, focusing on using virus-like particles containing therapeutic mRNA for gene and vaccine delivery.

Research topics

• Chemistry
• Physics
• Biology
• Materials science
• Chemical physics

Selected publications

• A New Approach to In Vivo Transformation of Killer T Cells

  Journal of Molecular Biology · 2025-08-05 · 2 citations

  articleSenior author
  PublisherDOI

• How much genetic information in RNA form can be protected by a CCMV virus-like particle?

  PLoS ONE · 2025-12-10 · 1 citations

  articleOpen accessSenior authorCorresponding

  The capsid protein of cowpea chlorotic mottle virus (CCMV) has been used extensively for in vitro packaging of heterologous RNA. The associated virus-like particles (VLPs) are spherical with a 3nm-thick/28nm-diameter protein shell and are therefore limited in the amount of RNA they can package. As shown in earlier work, when RNA lengths are longer than ~3500nt the RNA is no longer self-assembled exclusively into a single VLP. Rather, it is shared by two or more 28nm-diameter capsids in the form of doublets, triplets, and higher-order multiplets, with the RNA threaded through the naturally- occurring ~1.5nm-diameter holes in the 180-subunit/icosahedrally-symmetric protein shells. Consistent with this fact we find in the present work that 3500nt is the maximum length of packaged RNA that is fully protected under strong RNase digestion conditions.

  PublisherDOI

• Connecting In Vitro and In Vivo Studies of Biomolecular Interaction and Assembly

  Journal of Molecular Biology · 2025-10-06

  editorial1st authorCorresponding
  PublisherDOI

• In Vitro and in Vivo Transformation of Killer T Cells

  SSRN Electronic Journal · 2025-01-01

  preprintOpen accessSenior author
  PublisherDOI

• <i>In Vivo</i> Delivery of Spherical and Cylindrical <i>In Vitro</i> Reconstituted Virus-like Particles Containing the Same Self-Amplifying mRNA

  Molecular Pharmaceutics · 2024-05-06 · 13 citations

  articleOpen accessCorresponding

  The dramatic effectiveness of recent mRNA (mRNA)-based COVID vaccines delivered in lipid nanoparticles has highlighted the promise of mRNA therapeutics in general. In this report, we extend our earlier work on self-amplifying mRNAs delivered in spherical in vitro reconstituted virus-like particles (VLPs), and on drug delivery using cylindrical virus particles. In particular, we carry out separate in vitro assemblies of a self-amplifying mRNA gene in two different virus-like particles: one spherical, formed with the capsid protein of cowpea chlorotic mottle virus (CCMV), and the other cylindrical, formed from the capsid protein of tobacco mosaic virus (TMV). The mRNA gene is rendered self-amplifying by genetically fusing it to the RNA-dependent RNA polymerase (RdRp) of Nodamura virus, and the relative efficacies of cell uptake and downstream protein expression resulting from their CCMV- and TMV-packaged forms are compared directly. This comparison is carried out by their transfections into cells in culture: expressions of two self-amplifying genes, enhanced yellow fluorescent protein (EYFP) and Renilla luciferase (Luc), packaged alternately in CCMV and TMV VLPs, are quantified by fluorescence and chemiluminescence levels, respectively, and relative numbers of the delivered mRNAs are measured by quantitative real-time PCR. The cellular uptake of both forms of these VLPs is further confirmed by confocal microscopy of transfected cells. Finally, VLP-mediated delivery of the self-amplifying-mRNA in mice following footpad injection is shown by in vivo fluorescence imaging to result in robust expression of EYFP in the draining lymph nodes, suggesting the potential of these plant virus-like particles as a promising mRNA gene and vaccine delivery modality. These results establish that both CCMV and TMV VLPs can deliver their in vitro packaged mRNA genes to immune cells and that their self-amplifying forms significantly enhance in situ expression. Choice of one VLP (CCMV or TMV) over the other will depend on which geometry of nucleocapsid is self-assembled more efficiently for a given length and sequence of RNA, and suggests that these plant VLP gene delivery systems will prove useful in a wide variety of medical applications, both preventive and therapeutic.

  PublisherOA PDFDOI

• Long ssRNA undergoes continuous compaction in the presence of polyvalent cations

  Biophysical Journal · 2023-07-27 · 2 citations

  articleOpen accessSenior author

  In the presence of polyvalent cations, long double-stranded DNA (dsDNA) in dilute solution undergoes a single-molecule, first-order, phase transition ("condensation"), a phenomenon that has been documented and analyzed by many years of experimental and theoretical studies. There has been no systematic effort, however, to determine whether long single-stranded RNA (ssRNA) shows an analogous behavior. In this study, using dynamic light scattering, analytical ultracentrifugation, and gel electrophoresis, we examine the effects of increasing polyvalent cation concentrations on the effective size of long ssRNAs ranging from 3000 to 12,000 nucleotides. Our results indicate that ssRNA does not undergo a discontinuous condensation as does dsDNA but rather a "continuous" decrease in size with increasing polyvalent cation concentration. And, instead of the 10-fold decrease in size shown by long dsDNA, we document a 50% decrease, as demonstrated for a range of lengths and sequences of ssRNA.

  PublisherDOI

• Spontaneous bilayer wrapping of virus particles by a phospholipid Langmuir monolayer

  The European Physical Journal E · 2023-12-01

  articleOpen access

  Abstract We report here the spontaneous formation of lipid-bilayer-wrapped virus particles, following the injection of “naked” virus particles into the subphase of a Langmuir trough with a liquid monolayer of lipids at its air–water interface. The virus particles are those of the well-studied cowpea chlorotic mottle virus, CCMV, which are negatively charged at the pH 6 of the subphase; the lipids are a 9:1 mix of neutral DMPC and cationic CTAB molecules. Before adding CCMV particles to the subphase we establish the mixed lipid monolayer in its liquid-expanded state at a fixed pressure (17.5 mN/m) and average area-per-molecule of (41Å 2 ). Keeping the total area fixed, the surface pressure is observed to decrease at about 15 h after adding the virus particles in the subphase; by 37 h it has dropped to zero, corresponding to essentially all the lipid molecules having been removed from the air–water interface. By collecting particles from the subphase and measuring their sizes by atomic force microscopy, we show that the virus particles have been wrapped by lipid bilayers (or by two lipid bilayers). These results can be understood in terms of thermal fluctuations and electrostatic interactions driving the wrapping of the anionic virus particles by the cationic lipids. Graphical Abstract

  PublisherOA PDFDOI

• Designing Amphiphilic Conjugated Polyelectrolytes for Self-Assembly into Straight-Chain Rod-like Micelles

  Macromolecules · 2023-04-12 · 6 citations

  article

  Semiconducting polymers are a versatile class of materials that are used in many (opto)electronic applications, including organic photovoltaics. However, they are inherently disordered and suffer from poor conductivities due to bends and kinks in the polymer chains along the conjugated backbone, as well as disorder at grain boundaries. In an effort to reduce polymer disorder, we developed a method to straighten polymer chains by creating amphiphilic conjugated polyelectrolytes (CPEs) that self-assemble in water into worm-like micelles. The present work refines our design rules for self-assembly of CPEs. We present the synthesis and characterization of a straight, micelle-forming polymer, a derivative of poly(cyclopentadithiophene-alt-thiophene) (PCT) bearing two ammonium-charged groups per cyclopentadithiophene unit. Solution-phase self-assembly of PCT into micelles is observed by both small-angle X-ray scattering (SAXS) and cryo-electron microscopy (cryo-EM), while detailed SAXS fitting allows for characterization of intra-micellar interactions and inter-micelle aggregation. We find that PCT displays significant chain straightening thanks to the lack of steric hindrance between its alternating cyclopentadithiophene and thiophene subunits, which increases the propensity for the polymer to self-assemble into straight rod-like micelles. This work extends the availability of micelle-forming semiconducting polymers and points to further enhancements that can be made to obtain homogeneous nanostructured polymer assemblies based on cylindrical micelles.

  PublisherDOI

• The In Vitro Packaging of “Overlong” RNA by Spherical Virus-Like Particles

  Springer series in biophysics · 2023-01-01 · 1 citations

  book-chapterSenior author
  PublisherDOI

• Multiple Nucleocapsid Structural Forms of Shrimp White Spot Syndrome Virus Suggests a Novel Viral Morphogenetic Pathway

  International Journal of Molecular Sciences · 2023-04-19 · 11 citations

  articleOpen access

  White spot syndrome virus (WSSV) is a very large dsDNA virus. The accepted shape of the WSSV virion has been as ellipsoidal, with a tail-like extension. However, due to the scarcity of reliable references, the pathogenesis and morphogenesis of WSSV are not well understood. Here, we used transmission electron microscopy (TEM) and cryogenic electron microscopy (Cryo-EM) to address some knowledge gaps. We concluded that mature WSSV virions with a stout oval-like shape do not have tail-like extensions. Furthermore, there were two distinct ends in WSSV nucleocapsids: a portal cap and a closed base. A C14 symmetric structure of the WSSV nucleocapsid was also proposed, according to our Cryo-EM map. Immunoelectron microscopy (IEM) revealed that VP664 proteins, the main components of the 14 assembly units, form a ring-like architecture. Moreover, WSSV nucleocapsids were also observed to undergo unique helical dissociation. Based on these new results, we propose a novel morphogenetic pathway of WSSV.

  PublisherOA PDFDOI

Recent grants

• Sizes of Viral Genomes and Strengths of Viral Capsids

  NSF · $750k · 2008–2010

• Statistical Mechanics of Colloidal Networks and Limited-Size Clusters

  NSF · $400k · 2000–2004

• FLYBASE: A DROSOPHILA GENOMIC AND GENETIC DATABASE

  NIH · $18.0M · 1992–2014

• How Do Genome and Capsid Fluctuations Determine the Translation Efficiencies of RNA Viruses?

  NSF · $766k · 2017–2021

• Self-Assembly and Packaging of RNA and DNA in Viruses and Virus-like Particles

  NSF · $570k · 2011–2014

Frequent coauthors

• Charles M. Knobler

  University of California, Los Angeles

  98 shared

• Avinoam Ben‐Shaul

  85 shared

• Richard C Lewontin

  61 shared

• Anthony Jf Griffiths

  60 shared

• David T Suzuki

  39 shared

• William E. McMullen

  35 shared

• Jeffrey H Miller

  33 shared

• Rees F. Garmann

  San Diego State University

  31 shared

Education

• Ph.D., Chemistry

  University of Chicago

  1970

• B.S., Chemistry

  Harvard University

  1967

Awards & honors

• Alfred P. Sloan Research Fellow (1974)
• Camille and Henry Dreyfus Teacher-Scholar Award (1976)
• Glenn T. Seaborg Award (1981)
• Hanson-Dow Distinguished Teaching Award (1986)
• American Physical Society Fellow (1987)