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Prof Lorna Dougan
Prof David Brockwell
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
Background: The accumulation of low molecular mass compounds is known to be a common strategy used by microorganisms to cope with extreme environments and stressful conditions, such as high osmolarity or elevated temperature. Extremophilic (extreme-loving) organisms make use of specific compatible solutes to survive. These solutes are generally negatively charged, whereas mesophiles accumulate primarily neutral solutes. This suggests that the unique charged solutes of extremophiles, such as hyperthermophiles, were especially selected through evolution to preserve cell components at high temperature.
Objectives: This project will develop quantitative biophysical approaches to compare the structure, stability and dynamics of hyperthermophilic proteins in the presence of relevant compatible solutes. We will make use of protein engineering and single molecule force spectroscopy to characterise the stabilty and dynamics of the protein and provide a detailed understanding of the energy landscape of the system.
Impact: The use of compatible solutes to improve protein stability is a well established practice for many biotechnological and clinical applications. However, the molecular mechanisms that govern this stabilization remain elusive. A bespoke force-clamp atomic force microscopy (AFM) instrument will be used to examine the conformational dynamics of single extremophilic proteins. The development of these methods will deliver fundamental insights into the mechanisms of extremophile adaptation, identification of new solutes for protein stabilization and storage, in addition to developing research tools that will be exploited in synthetic biology and bionanotechnology.
The project will be embedded within an active research group at Leeds whose focus is Life in Extreme Environments, providing the optimum research environment for this ambitious project. For more info: email Dr Lorna Dougan and/or look at www.mnp.leeds.ac.uk/ldougan
Objectives: This project will develop quantitative biophysical approaches to compare the structure, stability and dynamics of hyperthermophilic proteins in the presence of relevant compatible solutes. We will make use of protein engineering and single molecule force spectroscopy to characterise the stabilty and dynamics of the protein and provide a detailed understanding of the energy landscape of the system.
Impact: The use of compatible solutes to improve protein stability is a well established practice for many biotechnological and clinical applications. However, the molecular mechanisms that govern this stabilization remain elusive. A bespoke force-clamp atomic force microscopy (AFM) instrument will be used to examine the conformational dynamics of single extremophilic proteins. The development of these methods will deliver fundamental insights into the mechanisms of extremophile adaptation, identification of new solutes for protein stabilization and storage, in addition to developing research tools that will be exploited in synthetic biology and bionanotechnology.
The project will be embedded within an active research group at Leeds whose focus is Life in Extreme Environments, providing the optimum research environment for this ambitious project. For more info: email Dr Lorna Dougan and/or look at www.mnp.leeds.ac.uk/ldougan
Funding Notes
4 year BBSRC studentship, under the White Rose Mechanistic Biology DTP.
The successful applicant will receive fees and stipend (c.£13590 for 2013-14). The PhD will start in Oct 2013.Applicants should have, or be expecting to receive, a 2.1 Hons degree in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support.
There are 2 stages to the application process. Please see our website for more information:
http://www.fbs.leeds.ac.uk/gradschool/keywords/mnuFindaphd.php
The successful applicant will receive fees and stipend (c.£13590 for 2013-14). The PhD will start in Oct 2013.Applicants should have, or be expecting to receive, a 2.1 Hons degree in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support.
There are 2 stages to the application process. Please see our website for more information:
http://www.fbs.leeds.ac.uk/gradschool/keywords/mnuFindaphd.php
References
T. Hoffmann and L.Dougan, (2012) Single molecule force spectroscopy using polyproteins, ChemSocRev, 41, 4781
J.J. Towey, A.K.Soper and L. Dougan, Molecular insight into the hydrogen bonding and micro-segregation of a cryoprotectant molecule, Journal of Physical Chemistry B, 2012
Sadler, D. Petrik, E., Taniguchi, Y. Pullen J., Kawakami, M., Radford, S. and Brockwell D. (2009) Identification of a mechanical rheostat in the hydrophobic core of protein L. J Mol Biol 393:237-248.
J.J. Towey, A.K.Soper and L. Dougan, Molecular insight into the hydrogen bonding and micro-segregation of a cryoprotectant molecule, Journal of Physical Chemistry B, 2012
Sadler, D. Petrik, E., Taniguchi, Y. Pullen J., Kawakami, M., Radford, S. and Brockwell D. (2009) Identification of a mechanical rheostat in the hydrophobic core of protein L. J Mol Biol 393:237-248.
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Career overview
Professor Lorna Dougan is a physicist who completed her MPhys and PhD at the University of Edinburgh. She has received several prestigious awards, including the Water Woman Award for Research Excellence in 2020, the British Biophysical Society Young Investigator Medal in 2018 for her research on the physics of living systems, and the Royal Society of Chemistry MacroGroup UK Young Researchers Medal in 2013. In 2015, she was awarded the Medical Research Council and Royal Society Suffrage Science Award. Professor Dougan currently leads an Engineering Physical Sciences Research Council Fellowship focused on exploring multiscale biomechanics and has previously led a European Research Council Fellowship in Extreme Biophysics.
Research interests
Professor Dougan''s research focuses on hierarchical biomechanics, extreme biophysics, liquid structure, life in extreme environments, and synthetic biology. She leads an Engineering Physical Sciences Research Council Fellowship to explore multiscale biomechanics and has previously led a European Research Council Fellowship in extreme biophysics. Her multidisciplinary research group develops tools to investigate multiscale mechanics, single molecule manipulation techniques, and neutron scattering to understand the physics of living systems. The group studies hierarchical biomechanics, self-assembly, and the structure and dynamics of molecules in aqueous solutions, addressing both simple and complex systems. Professor Dougan is also involved in science communication and leads an EPSRC public engagement champion grant aimed at exploring creativity in STEM.
Hierarchical Biomechanics
Extreme Biophysics
Water
Aqueous Solutions
Cryopreservation
Biomolecular Self-Assembly
Protein Folding
Extremophiles
Single Molecule Force Spectroscopy
Multiscale Mechanics
Life in Extreme Environments
Synthetic Biology
Science Communication
Arts-Science Collaboration
Neutron Scattering.
Career overview
Professor David Brockwell is a Professor of Biochemistry and Molecular Biology at the University of Leeds, where he has been a faculty member since 2004. He completed his BSc in Pharmacy at the University of Manchester, followed by a pre-registration year at St Bartholomew''s Hospital in London, qualifying as a pharmacist in 1993. He returned to the University of Manchester for his PhD research, supervised by Dr Jill Barber, focusing on the biophysical effects of protein perdeuteriation. After a brief postdoctoral position at the same laboratory, he worked as a postdoc at the University of Leeds in Professor Sheena Radford''s lab for six years, where he began investigating force-induced unfolding and remodelling of proteins. In 2004, he was appointed to a joint URF/Lecturer position at Leeds and became an Associate Professor in 2012. With over 15 years of experience, Professor Brockwell''s research primarily investigates the effects of force on proteins and their aggregation, resulting in more than 45 publications in the field. His expertise encompasses protein (un)folding, force in biology, outer membrane protein biogenesis, biopharmaceutical aggregation and engineering, and protein hydrogels.
Research interests
Professor Brockwell''s research focuses on several key areas within biochemistry and molecular biology. His work investigates the effects of mechanical force on proteins and their complexes, utilising atomic force microscopy (AFM) to measure the mechanical properties of single protein molecules. He has explored how proteins with similar stability to chemical denaturants can exhibit different behaviours when subjected to force, and has studied the mechanical gating of outer membrane transporters. In the realm of membrane protein folding, Professor Brockwell examines the folding and insertion processes of bacterial outer membrane proteins (OMPs), collaborating with other researchers to understand how periplasmic chaperones and the b-barrel assembly machinery facilitate these processes. His research also addresses the challenges in biopharmaceutical manufacture, particularly how environmental changes can lead to unwanted protein unfolding and aggregation, which is critical in the biopharmaceutical industry. He collaborates with colleagues to investigate flow-induced aggregation and the manufacturability of biopharmaceuticals. Additionally, Professor Brockwell''s interests extend to protein hydrogels, which have applications in tissue engineering and drug delivery. He is working on developing hydrogels from folded globular proteins to exploit their full functional spectrum, including catalysis and ligand binding.
Biochemistry
Molecular Biology
Protein Folding
Protein Unfolding
Force in Biology
Outer Membrane Protein Biogenesis
Biopharmaceutical Aggregation
Protein Engineering
Protein Hydrogels
Mechanical Properties of Proteins
Membrane Protein Folding
Biopharmaceutical Manufacture
Hydrodynamic Forces
Protein Aggregation
Tissue Engineering
Stimulus-Responsive Hydrogels
Ligand-Triggered Actuators
Drug Delivery
Periplasmic Chaperones
Bacterial Outer Membrane Proteins
AFM (Atomic Force Microscopy)
Protein Stability
Protein Dynamics.
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