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Engineered antibodies for improved immunotherapies against breast cancer


Project Description

Antibodies have emerged as a major drug class for the treatment of human cancers and inflammatory disorders. Many of the therapeutic antibodies rely on their immune recruitment properties, engaging the host’s immune cells to antagonise tumours or dampen autoimmune responses (e.g. in autoimmune disorders. However, limitations arise from the tumour microenvironment where proteinases can cleave targeted antibodies. In a parallel phenomenon, bacteria have evolved proteinases and glycosylhydrolases that specifically degrade human immunoglobulins. By understanding these and other resistance mechanisms, we aim to develop new therapeutic antibodies to a range of diseases with an emphasis on improving antibody therapy against breast cancer.

The PhD candidate will aim to characterise the molecular basis for the specificity of IgG-degrading enzymes as well as elucidating the structure of emerging therapeutic antibodies that have been engineered for enhanced therapeutic properties. A major aim of the project is determination of structure by X-ray crystallography. Based at the School of Biological Sciences, the successful candidate will have access to a number of complementary techniques that includes structural biology, proteomics and protein engineering technologies. This will help in the design of novel antibodies that will then be tested by collaboration with the Southampton Centre for Cancer Immmunology (CIC).

The candidate would be expected to gain independence on the full work-flow in protein structure determination by X-ray crystallography and, overtime, will take responsibility for some aspects of running of the crystallography laboratory. The candidate will be a key contributor to the growing collaboration between Biological Sciences and the Centre for Cancer Immmunology. The candidate would be expected to write scientific articles and contribute to grant applications. The post will be partly funded by Against Breast Cancer (www.againstbreastcancer.org.uk) and the candidate will be expected to contribute to their public engagement activities.

Funding Notes

The project is funded for 4 years and welcomes applicants from the UK and EU who have or expect to obtain at least an upper second class degree in Biological and Molecular Sciences or allied subjects. Funding will cover fees, and a stipend at £18,000 per annum.

Due to funding restrictions this position is only open to UK/EU applicants.

References

Applications for a PhD in Biological Sciences should be submitted online at:
https://studentrecords.soton.ac.uk/BNNRPROD/bzsksrch.P_Login?pos=4973&majr=4973&term=201920 Please place Prof. Max Crispin’s name in the field for proposed supervisors.

General enquiries should be made to Prof. Max Crispin at [email protected] or Dr Ivo Tews Tews at [email protected] Any queries on the application process should be made to [email protected]

Applications will be considered in the order that they are received, and the position will be considered filled when a suitable candidate has been identified.

The University of Southampton and Biological Sciences both hold an Athena Swan Silver Award, respectively, demonstrating their commitment to provide equal opportunities and to advance the representation of women in STEM/M subjects: science, technology, engineering, mathematics and medicine. Due consideration will be given to applicants who have taken a career break. University benefits include onsite childcare facilities, state-of-the-art on-campus sports, arts and culture facilities, a full programme of events and a range of staff discounts.

How good is research at University of Southampton in Biological Sciences?

FTE Category A staff submitted: 34.80

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

Click here to see the results for all UK universities

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