Mark Leake
Professor Anniversary Chair of Biological Physics

Profile

Career

MA Natural Sciences (Cantab), MSc Medical Physics (Surrey), MA (Oxon), PhD Biophysics (London), MInstP, FRMS

Summary of expertise

  • Biological physics
  • Single-molecule biophysics
  • Biophotonics/bespoke optical microscopy
  • Superreolution in cellulo imaging

Previous posts

  • 2007-2012 Royal Society University Research Fellow,Oxford University,UK
  • 2007-2012 Senior Research Fellow and Principal Investigator in Systems Biology,Oxford University,UK
  • 2008-2011 Hertford CollegeOxfordScience Research Fellowship
  • 2007-2009 Principal Investigator of the Interdisciplinary Research Collaboration in Bionanotechnology,Oxford University,UK.
  • 2006-2007 Leverhulme Trust Early Career Fellow,Oxford University,UK
  • 2003-2006 Interdisciplinary Research Collaboration Research Fellow in Bionanotechnology,Oxford University,UK
  • 2002-2003 Deutsche Forschungsgemeinshaft Postdoctoral Research Fellow, Ruprect-Karls-Universität Heidelberg, Germany.
  • 2001-2002 Postdoctoral Research Fellow in Biological Physics,Oxford University,UK.

Honours

  • European Biophysical Societies Association (EBSA), Young Investigator Finalist, 2011
  • Young Investigator Award British Biophysical Society, 2010
  • Fellow of the Royal Microscopical Society (FRMS), 2008
  • HertfordCollegeScience Research Fellowship, 2008
  • Royal Society University Research Fellowship, for independent research, 2007
  • Daiwa Adrian Anglo-Japanese Prize. Co-author for bacterial motor research, 2007
  • Leverhulme Trust Early Career Fellowship for independent research, 2006

University roles

  • Anniversary Chair of Biological Physics (between Physics and Biology Depts)
  • Yorklead PI in White Rose Consortium doctoral training student network in ‘Single-molecule methods’

Research

Overview

Research groupBiological Physics Group

I am the Anniversary Professorial Chair of Biological Physics, heading an interdisciplinary science team across the Depts of Physics and Biology. The group specializes in developing and applying novel forms of optical microscopy to investigate complex biological processes at the level of single molecules.

Our research specializes on the theme of 'Single-molecule cellular biophysics'. This is becoming a highly topical area of life sciences research which strives to move towards a greater physiological relevance to single molecule biophysics experimentation, either by combining in vivo cellular biology techniques with those of cutting-edge single molecule biophysics or by creating a  greater level of molecular complexity to single biomolecule experiments in vitro, and is in effect emerging as a novel disciple in its own right which is likely to increase in application significantly over the next few years as these techniques become more widely used. We use a range of cutting-edge biophotonics and photophysical methods in combination with state-of-the-art genetics. Our group has a depth of expertise in physics applied to biology at the single molecule level, and has  worked on bio-molecule mechanical manipulation and force spectroscopy using both AFM and laser-tweezers, low-light fluorescence imaging in vivo and customized advanced microscope design involving development of nanometre length scale imaging with millisecond time resolution. We have a reputation in single molecule investigations on living cells involving several multi-institutional collaborations.

General biological questions of interest to us involve addressing the molecular basis of the cell, seeing how single molecule properties in a living organism scale up to bring about whole-organism functionality, striving to bridge our gap in understanding between molecular biology and cell science in a rational, predictive context. These  pose some of the hardest and most fundamental challenges to the future of biophysics research. Full understanding of processes in living organisms is only achievable if all molecular interactions are considered. Cell biology strives to cultivate a full insight into the mechanisms of living cells by investigating interactions that elicit and direct cellular events, though to date the shear complexity of biological systems has caused precise single-molecule experimentation to be far too demanding, instead focusing on studies of single systems using relatively crude bulk ensemble-average measurements. One way forward which we're currently pushing is to monitor several biological systems simultaneously in living, functioning cells using more powerful and precise single molecule techniques, in effect investigating systems level biology from a bottom-up molecular level, eradicating noise rife in systems biology data associated with cell population stochasticity.

Using novel microscopy techniques and state-of-the-art genetics (Nature 2006, 443, 355; PNAS 2008, 105, 15376; Science 2010, 328, 498, Science 2012, 338, 528), we have developed means to monitor single proteins within a living, functioning cell and to observe exchange with other molecules in a complex, functioning biological system. Our objectives are  to drive these optical techniques to a much higher level to permit fast, real-time, molecular in vivo imaging of several different proteins in multiple, complex biological systems, to establish and validate mathematical models of complex systems down to the molecular level, and to push forward the genetic development of cell strains for use in these 'optical proteomics' studies. Currently we are targeting several biological systems including motility, protein transport, cell signalling and bioenergetics, but over half of our work is devoted to studies of  and the 'lifecycle' of the DNA molecule through from replication to segregation. 

Our primary experimental technique utilizes advanced approaches of  fluorescence microscopy such as total-internal-reflection fluorescence (TIRF) and Slimfield imaging, generally necessitating customized construction, combined with cutting-edge Fluorescent protein  fusion molecular genetics technology.

Projects

  • Development of millisecond 3D superresolution 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
  • Studying cell membrane biophysics at the nanoscale
  • Investigating live-cell molecular bio-energetics

External activities

Memberships

National/International Committee Roles

  • Physics of Life EPSRCUKnetwork biological physics steering panel member
  • IoP Biological Physics Group committee member
  • British Biophysics Society (BBS) steering panel member
  • Light Microscopy committee member of the Royal Microscopical Society
  • Royal Society Research Grants Scheme Biological Sciences Board
  • Royal Society International Exchange Scheme Review Committee

‌‌‌Mark Leake

Department of Physics
University of York
Heslington
York
YO10 5DD
U.K.

mark.leake@york.ac.uk
Tel: +44 (0)1904 322697
Fax: +44 (0)1904 322214
Room: P/C102