Cell trafficking is vital to all multicellular life and key in diseases such as cancer. In this PhD project, you will devise new methods to study how immune cells that circulate in the blood stream find and bind to sites of inflammation and how cancer cells hijack the system to metastasize. This is a formidable challenge that requires multiple disciplines – physics, biology and chemistry – to work hand in hand.
A key factor in this process are specialised receptor molecules on the surface of the circulating cells that recognize a polysaccharide-rich coat lining the blood vessel walls. The mechanical properties of the receptors and the blood vessel coat are critical for proper adhesion under the shear stress of blood flow. Yet, what these are and how they control selective cell trafficking is not well understood.
A key technique to probe the nanomechanics of individual molecular bonds along with the mechanical properties of tissues is atomic force microscopy (AFM). Laminar flow assays and optical microscopy, on the other hand, enable collective interactions to be probed. In a multidisciplinary environment, you will learn to create bottom up biosynthetic models of the circulating cell-blood vessel interface that enable well defined biophysical experiments using AFM and optical microscopy. The experimental work will be accompanied by theoretical work to aid the analysis of the experimental data and develop an understanding of the molecular and soft matter physics underpinning selective cell trafficking.
In this project, you will put soft matter physics to the benefit of understanding biology. This will provide new insight into how cells trafficking is regulated, and ultimately help to devise new strategies to interfere with diseases such as cancer and chronic inflammation, and to design advanced biomaterials that guide cells for tissue repair.
Suitable CANDIDATES would have a background in biophysics, soft matter physics, physical chemistry, biomedical engineering or a closely related field, and keen interest in multidisciplinary work. Experience in single molecule biophysics or advanced optical microscopy is an advantage.
PHYSICS AND BIOLOGICAL SCIENCES AT LEEDS. The University of Leeds operate “low-wall” principles with the aim of encouraging cross-disciplinary approaches to big science questions. This project will take place at the Faculty of Biological Sciences (http://www.fbs.leeds.ac.uk
) in tight collaboration with the Molecular and Nanoscale Physics Group (https://www.physics.leeds.ac.uk/research/groups/molecular-and-nanoscale-physics-group.html
). The Faculties offer superb facilities, provide a high quality research training environment and deliver an exceptional student education.
Please APPLY online, and include a CV, transcripts of your university record and contact details of two referees in your application. You do not need to provide a research proposal at this stage, but a motivation letter on why you want to join the project is desirable.
The studentship is for 3 years and covers academic fees and a stipend of £14,777 p/a. Applicants should have, or be expecting to receive, an undergraduate degree of at least 2.1 Hons level (or equivalent). A masters degree is an advantage.
Individuals interested in this project are encouraged to contact Dr. Ralf Richter ([email protected]) for further information. For questions related to the application process and eligibility, please contact Martha Smith ([email protected]).
1. H. S. Davies, D. Debarre, N. El Amri, C. Verdier, R. P. Richter and L. Bureau (2018) Elastohydrodynamic lift at a soft wall. Phys Rev Lett 120:198001.
2. F. Bano, S. Banerji, M. Howarth, D. G. Jackson and R. P. Richter (2016) A single molecule assay to probe monovalent and multivalent bonds between hyaluronan and its key leukocyte receptor CD44 under force. Sci Rep 6:34176.
3. G. V. Dubacheva, T. Curk, R. Auzély-Velty, D. Frenkel and R. P. Richter (2015) Designing Multivalent Probes for Tunable Superselective Targeting. Proc Nat Acad Soc USA 112:5579.