Faculty of Biological Sciences

Dr David Brockwell

BSc, PhD 1997, Manchester.
Associate Professor
School of Molecular and Cellular Biology

Contact:  Astbury 10.116, +44(0) 113 34 37821, email address for  

You can read more about Dr Brockwell's interests here:
www.fbs.leeds.ac.uk/staff/Brockwell_DJ

Research Interests

The effects of force on proteins and their complexes; extremophilic proteins; membrane protein folding and folding factors.

Currently research in the group is following three themes which are described below. If you are interested in joining the lab to study for a PhD find studentship and eligibility details here.

Our Asylum Research AFM instruments are housed in the School of Physics and Astronomy at Leeds.  This allows regular contact with colleagues Simon Connell, Lorna Dougan and Neil Thomson.   Areas from which our research benefits from the input of colleagues in Leeds include the Structural Molecular Biology and Integrative Membrane Biology groups.

The effects of force on proteins and their complexes

Mechanical unfolding: in vitro many proteins are required to resist or respond to mechanical stimuli. Over the last decade the development of atomic force microscope (AFM) instruments with high force sensitivity and sub-nanometre distance resolution has allowed the mechanical properties of single protein molecules to be measured. This work has revealed that proteins with similar stability to chemical denaturants can behave very differently when unfolded by the AFM. We are interested in finding out why some proteins are able to resist greater unfolding forces than others to understand how Nature uses mechanical denaturation to accelerate protein unfolding. In addition, we also use this information to rationally design proteins with novel mechanical properties.

Publication: Identification of a mechanical rheostat in the hydrophobic core of protein L.  Sadler et al. (2009) J Mol Biol 393:237-248.

 

Exploring protein-ligand interactions: in addition to characterising the behaviour of proteins under mechanical extension we have also started to measure the mechanical strength of the non-covalent interactions between proteins and their ligands. In particular we are interested in finding out how very strong interactions are broken apart on timescales fast enough to be biochemically useful. To do this we specifically immobilise one protein partner onto a surface and the other onto the tip of the AFM cantilever. This work has revealed that highly avid complexes can be rapidly broken apart by the application of small forces that are accessible to Nature.

Publication: A force-activated trip switch triggers rapid dissociation of a colicin from its immunity protein.   Farrance et al. (2013) PLoS Biol 11:e1001489.

Properties of extremophilic proteins

Life is found in the harshest of environments: low and high temperatures (< 0 and > 100 °C, respectively), low pH (< pH 2) and high salt concentrations (> 2M).  For many uni-cellular organisms, adaption to survival in these environments often occurs by the evolution of extremophilic proteins e.g. those that remain functional at low or high temperatures (psychrophilic and hyperthermophilic proteins).  In a collaboration with Lorna Dougan (Physics, Leeds), we have recently started to examine the biophysical and mechanical properties of a range of extremophilic proteins.

Publication: Single-molecule force spectroscopy identifies a small cold shock protein as being mechanically robust. Hoffmann et al. (2013) J Phys Chem B 117:1819−1826.

Membrane protein folding and folding factors

Despite their ubiquity and importance as cellular gatekeepers, progress in understanding how membrane proteins fold into the narrow ensemble of structures required for their function is slow. In a collaboration with Professors Steve Baldwin and Sheena Radford we are examining the folding and insertion of the bacterial outer membrane protein PagP into liposomes and how periplasmic chaperones facilitate this process.

Publication: Malleability of the folding mechanism of the outer membrane protein PagP: parallel pathways and the effect of membrane elasticity.  Huysmans et al. J Mol Biol 416:453-463.

 

Faculty Research and Innovation



Studentship information

See also:

Modules managed

BIOC1303 - Introductory Biochemistry: Problem Solving and Data Handling

Modules taught

BIOC1301 - Introductory Integrated Biochemistry: the Molecules and Processes of Life
BIOC1302 - Introductory Biochemistry: Practical Skills
BIOC1303 - Introductory Biochemistry: Problem Solving and Data Handling
BIOC2301 - Intermediate Integrated Biochemistry
BIOC2302 - Intermediate Biochemistry: Practicals
BIOC2303 - Intermediate Biochemistry: Skills
BIOC3111/12 - ATU - Protein Dynamics
BIOC3160 - Laboratory/Literature/Computing Research Project
BIOC3221/22/BIOL3210 b - ATU - Folding & Diseases
BIOL3397 - Biotechnology Research Project
BIOL3398 - Research Tools and Applications
BIOL3399 - Extended Research Project Preparation
BIOW5901X - Foundation module
BMSC2120 - Scientific Skills
FOBS1135/BIOL1112 - The Basis of Life/The molecules of life

Committees

Member of Masters Taught Student Education Committee (Exams Officer: Bioscience)

Centre membership: The Astbury Centre for Structural Molecular Biology

Postgraduates

Ciaran Doherty (Primary supervisor) 65% FTE
Samuel Hickman (Primary supervisor) 34% FTE
Matthew Hughes (Primary supervisor) 50% FTE
Katherine Kendrick (Primary supervisor) 100% FTE
Leon Willis (Primary supervisor) 34% FTE
John Dobson (Co-supervisor) 50% FTE
Jessica Ebo (Co-supervisor) 50% FTE
Anna Higgins (Co-supervisor) 50% FTE
James Horne (Co-supervisor) 50% FTE
Julia Humes (Co-supervisor) 50% FTE
Robert Schiffrin (Co-supervisor) 50% FTE
Michael Wilson (Co-supervisor) 50% FTE
Alexander Wright (Co-supervisor) 50% FTE