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Prof Paul Beales
Prof Stephen Muench
No more applications being accepted
Funded PhD Project (European/UK Students Only)
About the Project
Membrane proteins make up approximately one third of proteins transcribed by the human genome and are the targets for a large proportion of drugs. However, to realize their full biotechnology potential, these proteins require inclusion within durable, native-like membrane environments that enable them to function.
Liposomes have the required biocompatibility but lack long-term stability, whereas robust polymersomes don’t provide a native-like bilayer. Recent work has demonstrated the feasibility of hybrid lipid-polymer membranes that combine the benefits of biocompatibility with durability. This project will develop these hybrid vesicles for functional reconstitution of membrane proteins into resilient platforms suitable for industrial applications.
The successful candidate will develop a comprehensive range of interdisciplinary skills in the physical chemistry and bionanotechnology of self-assembled membranes as well as biology expertise in producing and handling membrane proteins. Specific skills to be learnt include preparation and characterisation of self-assembled membranes and vesicles, expression and purification of membrane proteins, confocal fluorescence microscopy and cryo-transmission electron microscopy.
The project will be supervised by Dr Paul Beales (School of Chemistry), Dr Stephen Muench and Dr Lars Jeuken (Faculty of Biological Sciences). Please contact the supervisors for further information about this project.
Liposomes have the required biocompatibility but lack long-term stability, whereas robust polymersomes don’t provide a native-like bilayer. Recent work has demonstrated the feasibility of hybrid lipid-polymer membranes that combine the benefits of biocompatibility with durability. This project will develop these hybrid vesicles for functional reconstitution of membrane proteins into resilient platforms suitable for industrial applications.
The successful candidate will develop a comprehensive range of interdisciplinary skills in the physical chemistry and bionanotechnology of self-assembled membranes as well as biology expertise in producing and handling membrane proteins. Specific skills to be learnt include preparation and characterisation of self-assembled membranes and vesicles, expression and purification of membrane proteins, confocal fluorescence microscopy and cryo-transmission electron microscopy.
The project will be supervised by Dr Paul Beales (School of Chemistry), Dr Stephen Muench and Dr Lars Jeuken (Faculty of Biological Sciences). Please contact the supervisors for further information about this project.
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
Nam J., Vanderlick T.K. and Beales P.A.; Formation and dissolution of phospholipid domains with varying textures in hybrid lipo-polymersomes. Soft Matter 8, 7982-7988 (2012).
Nam J., Beales P.A. and Vanderlick T.K.; Giant Phospholipid/Block Copolymer Hybrid Vesicles: Mixing Behavior and Domain Formation. Langmuir 27 (1), 1-6 (2011).
Muench, S.P., Huss, M., Phillips, C., Song, C.F., Wieczorek, H., Trinick, J. & Harrison, M.A.; Cryo-electron microscopy of the vacuolar ATPase motor reveals its mechanical and regulatory complexity. J. Mol. Biol. 386, 989-999 (2009).
McMillan, D.G.G., Marritt, S.J., Butt, J.N., Jeuken, L.J.C.; Menaquinone-7 is a specific co-factor in the tetraheme quinol dehydrogenase CymA, J. Biol. Chem. 287, 14215-14225. (2012)
Nam J., Beales P.A. and Vanderlick T.K.; Giant Phospholipid/Block Copolymer Hybrid Vesicles: Mixing Behavior and Domain Formation. Langmuir 27 (1), 1-6 (2011).
Muench, S.P., Huss, M., Phillips, C., Song, C.F., Wieczorek, H., Trinick, J. & Harrison, M.A.; Cryo-electron microscopy of the vacuolar ATPase motor reveals its mechanical and regulatory complexity. J. Mol. Biol. 386, 989-999 (2009).
McMillan, D.G.G., Marritt, S.J., Butt, J.N., Jeuken, L.J.C.; Menaquinone-7 is a specific co-factor in the tetraheme quinol dehydrogenase CymA, J. Biol. Chem. 287, 14215-14225. (2012)
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Career overview
Professor Paul Beales is a Professor of Soft Matter and Biophysics at the University of Leeds, having joined the institution as a Senior Research Fellow in November 2010. He was promoted to Lecturer in 2015, Associate Professor in 2016, and then to his current professorship in 2022. Professor Beales obtained his PhD from the University of Edinburgh in 2005. Following this, he undertook postdoctoral appointments at Princeton University from 2005 to 2008 and at Yale University from 2008 to 2010. His research is highly interdisciplinary, focusing on the interface of physics, chemistry, and biology, particularly in understanding, characterising, and engineering soft and biological materials.
Research interests
Professor Beales'' research is highly interdisciplinary, focusing on the interface of physics, chemistry, and biology. His interests include understanding, characterising, and engineering soft and biological materials. He aims to explore fundamental physical properties and interactions of macromolecular and supramolecular structures in living systems. Additionally, he is involved in efforts to reconstitute cellular processes and functions within minimal systems and in designing novel materials with technological applications. A significant aspect of his work involves developing new materials for drug formulation and delivery, contributing to the advancement of smart medicines. Many of his projects centre around self-assembled membranes, which serve as models for biological membranes or facilitate the encapsulation of chemical cargo within vesicle architectures. He is particularly interested in vesicles for the development of novel technologies, including nanomedicines, nanoreactors, controlled release systems, and artificial cells.
Career overview
Dr Stephen Muench studied for an undergraduate degree in Biochemistry and Microbiology at the University of Sheffield in 1997, during which time he undertook an undergraduate research project in X-ray crystallography, fostering his strong interest in structural biology. He continued at Sheffield for his PhD studies, focusing on the development of new anti-malarial and toxoplasmosis compounds through X-ray crystallography. After a brief postdoctoral position in Sheffield studying the role of the GTPase EngA, he moved to Leeds in 2005 to learn electron microscopy (EM). During this time, he developed a keen interest in EM and its application for studying large membrane protein complexes, as well as new methodologies such as time-resolved cryoEM. Following the award of an MRC career development fellowship in 2010, he established his own research group with a strong interest in combining different techniques to study the structure and function of a wide range of protein targets. Dr Muench is currently an Associate Professor in Membrane Biology at the University of Leeds, where his group has worked on various systems and technologies, including the development of new small molecules, membrane protein scaffolds, biosensors, and time-resolved approaches. Major contributions to the field include the use of EM to drive inhibitor design for membrane proteins, development of time-resolved methodologies for cryoEM, and advancements in understanding sample preparation within single particle cryoEM.
Research interests
Dr Muench''s research focuses on structural biology, particularly the dynamics and conformational variability of large protein complexes. His work employs a combination of techniques, including X-ray crystallography and electron microscopy (EM), with an emphasis on time-resolved applications. He is involved in developing new approaches for sample preparation and time-resolved cryoEM studies, aiming to enhance the understanding of the structure/function relationship of medically important targets. Dr Muench''s research includes the development of time-resolved cryoEM methodologies, which allow for the trapping of dynamic protein states at various points in their movement. This involves collaboration with experts in engineering, mass spectrometry, and chemistry to create systems that can capture protein behaviours on the second, millisecond, and microsecond timescales. His group has also investigated the stability of samples for single particle cryoEM, revealing the time-dependent nature of sample stability and degradation. In addition, Dr Muench is focused on improving the study of membrane proteins, which are crucial for drug targeting but are less understood than soluble proteins. His research explores the use of styrene maleic acid (SMA) and related copolymers to extract and stabilise membrane proteins in a more native lipid environment. This work has led to significant advancements, including the first negative stain and sub-nanometre single particle cryoEM structure of an SMA-extracted membrane protein. Dr Muench''s interests also extend to structure-based drug design, where he aims to develop new small molecule inhibitors and understand disease-causing mutations across various diseases. His collaborative projects span multiple areas of biology, involving national and international partners, and include studies on TRPC channels, receptor tyrosine kinases, ABC transporters, and myosin, among others.
Membrane Biology
Structural Biology
Electron Microscopy
Membrane Proteins
Structure Based Drug Design
Time Resolved Electron Microscopy
Sample Preparation
X-Ray Crystallography
Protein Dynamics
CryoEM
Small Molecule Inhibitors
Protein Expression
Styrene Maleic Acid
Native Lipids
Drug Targeting
Biochemical Analysis
Protein Complexes
Biosensors
Method Development
Conformational Variability
Therapeutic Targets.
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