Joseph Research Group

Welcome!

Welcome to the Joseph Group at Princeton. We are part of the Department of Chemical and Biological Engineering and the Princeton Bioengineering Initiative.  

Research Overview

The goal of our research group is to determine the principles governing intracellular compartmentalization and to employ these rules for bioengineering. 

Systems of interest: We are particularly interested in the characterization of biomolecular condensates—compartments inside cells that lack physical membranes. These compartments are largely composed of proteins, RNA and other biomolecules and are thought to assemble via phase separation. Importantly, biomolecular condensates are linked to both healthy (e.g., RNA processing) and aberrant (e.g., neurodegenerative disorders) cellular functions. Thus, careful characterization of these compartments presents exciting opportunities for engineering new cellular functions, as well as for developing therapies to bypass condensate-linked disorders.

A leading aim of our research is to determine the physicochemical factors that dictate the fate of biomolecular condensates and to engineer strategies for regulating their properties. 

Group Approach

Molecular dynamics with Mpipi Model

To address these and other questions, we design computer simulations and develop theoretical approaches that enable us to interrogate intracellular compartments across a variety of spatiotemporal scales. Specifically, we integrate molecular dynamics and Monte Carlo-based techniques, as well as implement and design atomistic, coarse-grained, and minimal model representations of biomolecules. Using these tools, we investigate the factors that govern the formation, dissolution, and misregulation of biomolecular condensates. We then exploit the mechanistic insight to rationally design condensates with novel functions.

Our research lies at the intersection of biology, chemistry, physics, computer science and engineering and is therefore highly collaborative.

Recent Publications

2023

2022