... understanding life in molecular detail

Prof Lorna Dougan

Physics of Life, Extreme Conditions, Synthetic Biology

We are developing single molecule manipulation techniques and neutron diffraction to explore the physics of living systems. These powerful techniques are used to study biomolecular self-assembly and the structure and dynamics of molecules in aqueous solutions, in both simple and complex systems.

Current major projects include:
  • Life in extreme environments
  • Single molecule force spectroscopy
  • Biophysical mechanisms of cryopreservation
  • Development of tools and technology for synthetic biology
  • Biomolecule self-assembly


Single molecule force - clamp spectroscopy is a powerful new experimental tool that permits investigation of the mechanical stability and folding pathways of individual proteins. We use this technique to apply a stretching force between two points of a protein, unfolding the protein to an extended state. By measuring the unfolding and folding trajectories of individual proteins, insight can be gained into the physical mechanisms of protein folding.

Our recent studies have demonstrated that this technique can be used to capture the role of solvent molecules in protein folding and chemical reactions and provide insight into enzyme catalysis and solvent mediation in biological systems.


Many organisms that live in extreme environments have developed mechanisms that protect them from environmental stresses. We are completing neutron diffraction experiments combined with computational modelling to provide structural insight and single molecule force spectroscopy experiments to probe the mechanical stability of proteins in cryoprotectant environments. By combining these two approaches we hope to shed light into the molecular mechanisms of cryoprotection.


Life has adapted to a vast range of environmental conditions and it is now difficult to find any place on Earth devoid of life. Some conditions are extreme in the sense of being unfavourable to most eukaryotic life forms. The adaption of proteins played a key role in enabling extremophilic organisms to colonise such ecological niches. Understanding the physical properties of proteins from extremophilic organisms and their remarkable preservation capability is not only of fundamental interest, but also pivotal to our ability to rationally engineer biological materials for exploitation.

We are developing quantitative biophysical approaches to characterise the physical mechanisms of protein folding and stability in extreme environments. We use a force spectroscopy instrument to examine the conformational dynamics of single extremophilic proteins. This technique is used to apply a constant stretching force along the end-to-end length of the protein, driving proteins to a fully extended unfolded state. By examining single molecules one at a time, the individual dynamics of protein subpopulations can be measured, revealing information which may be crucial for designing ‘artificial’ extremophilic proteins.


We are developing a single molecule approach to provide new insight into the mechanisms of protein folding. By exploring the structural limitations of extremophilic proteins we aim to uncover universal rules determining how proteins fold. Such knowledge will be invaluable for the de novo design of proteins with desired properties. This work will reveal critical information on the physics and function of proteins and provide the foundations for developing biologically inspired materials.


Biological processes are intimately linked to the unique properties of water and the versatility with which it interacts with a wide variety of biomolecules. Neutron diffraction experiments can be utilised to obtain information on the average structural interactions of model systems in solution on a local length scale (1−10 Å). Our experiments have shown that simple aqueous solutions display complex hydrogen bonding patterns, where networks of water molecules percolate throughout the system.


Polyglutamine chains are currently associated with nine neurological disorders. In these diseases polyglutamine chains stick together to form extended structures. We have made the experimental discovery that polyglutamine chains form compact, collapsed structures which exhibit extreme mechanical stability. We are developing novel biophysical tools to study polyglutamine chains and uncover the origin of their extreme stability and their interaction with the surrounding solvent environment. We use neutron diffraction to gain atomistic-level structural insight into the system.

Detailed research programme                  Close ▲

Professor of Physics
MPhys (Edinburgh) PhD (Edinburgh)

Postdoctoral Research Associate (Columbia University, NY 2006-2008)
Lecturer Biological Physics (Leeds University, 2009-2010)
European Research Council Fellow (Leeds University, 2011-2016

E.C.Stoner 8.32
School of Physics
0113 343 8958


Selected Publications

  1. Tych KM, Batchelor M, Hoffmann T, Wilson MC, Paci E, Brockwell DJ, Dougan L Tuning protein mechanics through an ionic cluster graft from an extremophilic protein. Soft Matter 12 2688-2699 (2016)

  2. Hughes ML, Dougan L The physics of pulling polyproteins: a review of single molecule force spectroscopy using the AFM to study protein unfolding. Reports on progress in physics. Physical Society (Great Britain) 79 076601 (2016)

  3. Hoffmann T, Tych KM, Crosskey T, Schiffrin B, Brockwell DJ, Dougan L Rapid and Robust Polyprotein Production Facilitates Single-Molecule Mechanical Characterization ofβ-Barrel Assembly Machinery Polypeptide Transport Associated Domains. ACS Nano 9 8811-8821, (2015)

  4. Towey JJ, Soper AK, Dougan L Low-Density Water Structure Observed in a Nanosegregated Cryoprotectant Solution at Low Temperatures from 285 to 238 K Journal of Physical Chemistry B 120 4439-4448 (2016)