Department of Molecular and Cell Biology

Giancarlo Montovano
Robinson Lab
The Dual Binding Mode of the GTPase BipA is Controlled by Allosteric Regulation

Dr. Seth Fraden
Professor of physics, Brandeis University
Host: Carol Teschke

Symmetry-Guided Self-Assembly of DNA Origami and Proteins

We present a modular approach to synthetic self-assembly, using DNA and protein design to construct finite-sized nanostructures with a minimal number of unique monomers. Exploiting symmetry, we successfully assembled large icosahedral shells (100–1000 nm), inspired by Caspar and Klug’s 1962 virus structure theory. DNA origami enabled precise building block design, allowing us to control assembly pathways, kinetics, and yield. Cryo-EM validation and computational modeling revealed key factors governing self-assembly efficiency. These DNA-based capsids serve as an ideal realization of patchy particles whose geometry and interactions can be designed with sub-nanometer and kT precision. Expanding beyond icosahedra, we explored cylindrical and negatively curved surfaces. Now, leveraging AI-driven structure-based tools (Chroma, ESMfold, Boltz-1, AlphaFold3), we are testing whether these DNA origami principles apply to de novo protein design, pushing the frontiers of bioinspired materials engineering.

About Dr. Fraden:

Fraden is a professor of physics and co-interim chair of Engineering at Brandeis University, Waltham, MA. He served as director of the Bioinspired Soft Materials Research Science and Engineering Center (MRSEC) at Brandeis University from 2012 - 2024. Fraden received the 2008 Innovation Prize of the International Organization of Biological Crystallization for the development of microfluidic devices for high throughput protein crystallization. In 2020, Fraden was elected a Fellow of the American Physical Society for leadership in experimental soft matter physics. Fraden’s research focus is Bioinspired Soft Matter with a focus on (a) self-assembly in biomaterials with applications in antiviral therapy and drug delivery, (b) active matter with applications in soft robotics, (c) non-linear chemical dynamics and (d) the development of microfluidics for biotechnology with applications in protein crystallization.

Publications:

Economical routes to size-specific assembly of self-closing structures

Hierarchical assembly is more robust than egalitarian assembly in synthetic capsids

Programmable icosahedral shell system for virus trapping

Fraden website

John Briseno
Nyholm Lab

Dr. Dan Fabris
Harold S. Schwenk Sr. Distinguished Chair in Chemistry
Department of Chemistry, University of Connecticut
Host: Eric May

Hunting for new antivirals capable of disrupting the dynamic ensembles of regulatory RNAs

Summary: In many RNA viruses, genomic sequences corresponding to regulatory (i.e., non-coding) domains can fold alternative conformations responsible for different biological functions. Disrupting their interconversion would represent an excellent strategy for inhibiting such functions and interfering with the viral lifecycle. Owing to the intrinsic challenge of resolving the structural heterogeneity of these RNA dynamic ensembles, traditional drug-discovery approaches have thus far failed to provide effective leads. The talk will illustrate a suite of approaches based on native mass spectrometry (nMS) and Ion Mobility Spectrometry (IMS) MS, which afford the ability to distinguish the individual members of an RNA ensemble and to assess the effects of ligand binding on their mutual distribution. The talk will discuss the unique features that make nMS capable of taking accurate snapshots of all unbound/bound species present at equilibrium in solution when putative ligands are mixed with target RNAs. It will also show that combining nMS with IMS allows one to monitor RNA conformational landscapes before and after addition of ligand, which can reveal possible conformer selectivity. The information provided by these approaches will provide the foundations for developing conformer-specific antivirals with greatly reduced off-target toxicity.

Bio: Dan Fabris is a Professor and the Harold S. Schwenk Sr. Distinguished Chair in Chemistry. He received a Ph.D. at University of Padova (Italy) and trained as a post-doc at the National Research Council in Padova and the University of Maryland Baltimore County (UMBC). After raising to Professor at UMBC, he was recruited by University at Albany (SUNY) to become one of the founding members of The RNA Institute. He specializes on the development of novel approaches for the investigation of the structure/function relationships of RNA, which are based on mass spectrometric (MS) techniques. He pioneered native MS and crosslinking techniques for the structural elucidation of RNA and protein-RNA complexes that are not directly amenable to high-resolution techniques. At University of Connecticut since 2020, he is now exploring new strategies combining native MS with Ion Mobility Spectrometry (IMS) MS to investigate the effects RNA post-transcriptional modifications and ligand binding onto the structure and dynamics of regulatory RNAs.

Publication

Fabri Lab website