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Development of synthetic CCL2-conjugates to study and manipulate the function of monocytic cells.

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  • Full or part time
    Dr Butterworth
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

The goal of this project is to develop functionalised chemokine-based tools that can be used to selectively study and manipulate monocytic cells. The project is co-supervised by Sam Butterworth (Lecturer in Medicinal Chemistry, labs in School of Chemistry), Robin May (Professor of Infectious Disease in School of Biosciences) and Christopher Weston (Research Fellow in Centre for Liver Research).
Monocytes and related cells such as macrophages are an important class of leukocytes that play a key role in a wide range of biological processes, many of which have direct relevance to human wellbeing; including cognition, infection response, development/resolution of fibrosis, and immune suppression in tumours. Consequently, tools that allow the study of monocyte behaviour in native systems (for example through in vitro and in vivo imaging) or the selective manipulation of cell phenotype will have utility for biological researchers working on a wide array of problems.

This class of cells can be characterised in part by their use of the chemokine receptor CCR2, which has limited or no expression on other cell types. In order to signal, CCR2 binds and internalises the peptide CCL2. It has been previously demonstrated that recombinant a CCL2-mCherry fusion protein is effectively internalised by monocytes without damaging cell viability (PLOS One. 2012, 7(5), e37208), and we have now shown that a synthetic CCL2-fluorophore construct behaves in the same way.
The use of synthetic systems is superior to the use of fusion proteins as they are easily tuneable, allowing rapid access to a range of novel agents with variable function. The student will examine the potential of this system through the design, synthesis, characterisation and evaluation of novel synthetic chemokine derivatives.
The project would be particularly suitable for a student with a background in chemistry, who would like to develop their skills by working at the interface of chemistry and biology.

We anticipate that the student will be able to develop skills in a wide range of techniques including; Synthetic chemistry and analytical techniques, Peptide synthesis, Protein-specific synthetic and purification methodologies (Click chemistry, size exclusion purification, dialysis etc.), Protein analytical techniques (NMR, UV/Vis, MS, ion exchange chromatography), Cell culture and isolation, Transwell migration assays and other migration experiments, FACS analysis, Imaging of live and fixed cells.

For more information about Sam Butterworth please visit http://www.birmingham.ac.uk/schools/cem/staff/profile.aspx?ReferenceId=57497.

For more information about the School of Chemistry please visit
http://www.birmingham.ac.uk/schools/chemistry/index.aspx

To find out more about studying for a PhD at the University of Birmingham, including full details of the research undertaken in the School, the funding opportunities available for your subject, and guidance on making your application, you can order a copy of our Doctoral Research Prospectus, at: www.birmingham.ac.uk/drp

Funding Notes

This studentship is competition funded by the BBSRC MIBTP scheme: http://www.birmingham.ac.uk/research/activity/mibtp/index.aspx


Stipend: £14,057 per annum (plus travel allowance in year 1, and laptop)

The Midlands Integrative Biosciences Training Partnership (MIBTP) is a BBSRC-funded doctoral training partnership between the universities of Warwick, Birmingham and Leicester. It delivers innovative, world-class research training across the Life Sciences to boost the growing Bioeconomy across the UK.

To check your eligibility to apply for this project please visit:http://www2.warwick.ac.uk/fac/cross_fac/mibtp/pgstudy/phd_opportunities/application/

Applications should be made through the “apply to study here” link on: http://www.birmingham.ac.uk/postgraduate/courses/research/chemistry/chemistry-phd.aspx.

For other queries or advice on making your application, please contact:
[email protected]

How good is research at University of Birmingham in Chemistry?

FTE Category A staff submitted: 28.00

Research output data provided by the Research Excellence Framework (REF)

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