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Dr Joel Crossley

Position
University-funded Pathway to Independence Fellow
Areas of expertise
Single-molecule biophysics, Molecular dynamics simulations, Protein conformational dynamics and folding, Intrinsically disordered proteins, Protein misfolding and aggregation
Location
Garstang 10.135
Faculty
Biological Sciences
School
Molecular and Cellular Biology

Artistic rendering of the bacterial SecY protein embedded in the inner membrane during protein translocation. The lipid bilayer is shown as layered grey spheres, with SecY spanning the membrane. Red and green glowing spheres highlight fluorophores used in single-molecule FRET experiments, illustrating conformational changes during translocation.

Introduction

My research aims to understand how biomolecules function by directly observing their motions. I develop and apply advanced single-molecule fluorescence approaches to capture rapid conformational dynamics and transient interactions that are inaccessible to many established structural biology techniques. By integrating these measurements with molecular dynamics simulations, cryo-electron microscopy, and NMR spectroscopy, my work links molecular structure to function across multiple spatial and temporal scales.

As structural biology techniques have become increasingly powerful, a central challenge has emerged: translating detailed structural information into a dynamic understanding of function. This challenge is particularly acute because a large fraction of the human proteome is intrinsically dynamic or disordered, and these motions often underlie regulation, signalling, and disease. My research addresses this challenge by developing single-molecule fluorescence-based methods capable of probing millisecond and faster dynamics and by extending these measurements from simplified in vitro systems to complex environments, including living cells. By pushing structural biology into the time domain, my work provides a quantitative framework for understanding how molecular motions encode biological function and how their disruption leads to dysfunction in disease within native environments.

Current major projects

  • Development and application of advanced single-molecule fluorescence techniques
  • Mechanistic coupling of protein dynamics to function and disease-associated dysfunction