Mark Leake
Professor and Anniversary Chair of Biological Physics

Research

Overview

Coordinator - Physics of Life Group

I am a physicist by training but now address challenging biophysical and biochemical questions in a range of biological processes. Following initial undergraduate studies as a ‘natsci’ in the University of Cambridge in 1990-93, I gained my PhD in the biophysics of muscle proteins using optical tweezers techniques in King’s College London, with subsequent postdoctoral positions in Oxford and Heidelberg. I later gained independence as a Royal Society University Research Fellow in Oxford, leading research themes in single-molecule cellular biophysics and molecular scale optical proteomics, prior to becoming the new Anniversary Chair of Biological Physics at the University of York in 2013. I was the Director Founder of the Biological Physical Sciences Institute and am now the Coordinator of the Physics of Life Group.

General themes of my research involve (i) developing new biophysical instrumentation for addressing open biological questions, and (ii) applying these coupled to molecular biology and biochemical approaches to investigating questions concerning single molecules under physiologically relevant environments. I developed an exceptional cluster of biophysical techniques enabling the imaging and manipulation of single molecules with extraordinary control. This scientific success is founded on the single-molecule fluorescence microscopy with molecular and cellular manipulation and precision microfluidics technology. My team is in an ideal position to take the leap from studying single molecules to investigating entire complex biological processes at much higher length scales of cells and tissues.

For full details of my teams research check out our full publications – highlights include adding insight into the behaviour of the flagellar motor of bacteria [1,2], DNA replication, repair and remodelling [3-6], protein transport, oxidative phosphorylation, signal transduction, transcription and gene regulation [7], antibiotic tolerance and liquid-liquid phase condensates [8] and photosynthesis in viral-like nanomachines [9]. These advances have been underpinned by innovative tools and techniques enabling robust quantification of molecular and cellular properties: the spatiotemporal dynamics of functional molecular machines, their architecture and mechanical properties, the nature of their functional interactions, and their level of expression on a live cell-by-cell basis.

We also have exciting in vitro based projects emerging in DNA-protein interactions using a combination of AFM imaging, single-molecule FRET, tethered particle motion and an exciting new magneto-optical tweezers super-resolution imaging tool [10]. We are developing innovative experimental and computational pipelines to study liquid-liquid phase separation in biological systems [11], combining single molecule AFM imaging and molecular dynamics simulations to study topology changes in DNA about protein binding [12] 

1. Nature 437:916 (2005) 2. Nature 443:355 (2006)3. Science 328:498 (2010) 4. Science 338:528 (2012) 5. Nucleic Acids Research 10:210 (2019) 6. Nucleic Acids Research, Syeda & Wollman et al, in press (2019)7.eLife 6:e27451 (2017)  8.Mol Cell 73:1439. Plant Cell, Sun & Wollman et al, in press (2019)10.Photonics 2:758 (2015) 11. Science Advances 7(43):eabh2929 (2021) 12 Nucleic Acids Research 49:8684 (2021) 13 Interface 19:20220088

Projects

• Liquid-liquid phase separation in biological systems
• Development of millisecond 3D super-resolution imaging with photoblinking
• Designing and applying bio-molecular force transduction tools of laser/magnetic tweezers combined with nanoscale fluorescence imaging
• Probing cellular DNA replication/segregation using single-molecule biophysics
• Investigating molecular-level signal transduction in living cells
• Investigating DNA repair and remodelling processes
• Studying cell membrane biophysics at the nanoscale
• Probing cancer physics through imaging membrane receptors
• Studying infection and immunity through chemokines and synapses
• Probing liquid-liquid phase condensation in antibiotic tolerance and epigenetics
• Investigating live-cell molecular bio-energetics
• Developing optical tools to study emergent biological structures, including biofilms

Research group(s)

Physics of Life Group

External activities

Memberships

National/International Committee Roles

• Chair of the Physics of Life EPSRC UK Network 2021-present
• Chair of the IoP Biological Physics Group 2020 - present
• British Biophysics Society (BBS) steering panel member 2010 -present
• Light Microscopy committee member of the Royal Microscopical Society 2008 - present
• Royal Society Research Grants Scheme Biological Sciences Board 2016 - present
• Royal Society International Exchange Scheme Review Committee 2012 - present
• sLOLA BBSRC funding panel member 2020 - present
• EPSRC Peer Review College 2015 - present
• BBSRC Panel of Experts 2015 - 2018