Anti-oxidised LDL antibodies and their humanised fragments for the treatment of atherosclerosis: From in vitro mechanistic studies to in vivo functional molecular imaging

British Heart Foundation and National Heart and Lung Institute (NHLI)

4-year MRes/PhD Studentship, within the BHF doctoral training programme at Imperial College London

Applications are invited for a BHF 4-year MRes/PhD studentship starting in October 2023 at the National Heart and Lung Institute (NHLI) in partnership with the Bioengineering Department at Imperial College. There are four BHF DTP MRes/PhD studentship places (3 studentships funded by the BHF and 1 matched Departmental studentship). 

The Cardiovascular Sections of the National Heart and Lung Institute, Imperial College, are located within the Main Campus at South Kensington, the Brompton Campus, and Hammersmith/White City Campus. Bioengineering is also located at Main Campus at South Kensington and at White City. Students will have the opportunity to work in state-of-the-art facilities within a highly developed research environment where our ambition is to translate research findings to help those with cardiovascular diseases. All students benefit from a full programme of training in research and transferable skills organised through the Graduate School, the quality of which has been recognised several times at the Times Higher Education (THE) Awards. The student will join a well-established doctoral training program with bespoke teaching activities, seminars, mentors, and workshops.

Project summary

Atherosclerosis occurs when cholesterol builds up in blood vessels walls increasing the risk of cardiovascular disease and heart attacks and strokes. LDL cholesterol and its oxidised form (oxLDL) is particularly important in the development and severity of atherosclerosis. Cardiovascular disease is the biggest killer in the UK and around the world. This project will use innovative and novel approaches to image and manage low density lipoprotein (LDL) cholesterol in vascular and immune cells and in mouse models in vivo. This BHF 4-year MRes/PhD studentships comprises a 1-year MRes in Biomedical Research, followed by a linked 3-year PhD. During the MRes year, students undertake two laboratory projects which will prepare them for the PhD. The first project will be in Prof Mitchell’s laboratory, which will study the pharmacological and toxicological profiling of monoclonal antibody LO1 and its humanised Fab fragment in macrophages and endothelial cells. This antibody is the focus of the 4 year study and is targeted against oxidised LDL in atherosclerosis. The second project will be exploring the role of the antibodies in the interaction between oxLDL and LOX-1 in endothelial cells in vitro.

The Three year PhD project aims to study either LO1 or LO1-Fab against malondialdehyde (an oxidative stress epitope) oxLDL (MDA-LDL) affecting the rate of atherosclerosis progression and modification of disease biology in vivo, as well as exploring their role in trafficking of oxidised LDL through immunocomplex formation and mobility. The laboratory work will be mainly focused on in vivo passive immunisation, molecular imaging and ex vivo analysis as well as some mechanistic cellular work and immunohistochemistry. The main in vivo imaging modality will be Fluorescence Molecular Tomography and CT, using multiple targeting agents.

This is a translational programme, where the student will be exposed to high quality basic science and biological techniques, clinical translational techniques as well as imaging analysis. Dr Khamis will be principal supervisor and be responsible for the overall progress of the research towards completion. Professor Mitchell will be co-supervisor and responsible for the pharmacological and vascular biology aspects of the work. Professor Haskard will co-supervise.

Applicant Requirements

Applicants must hold, or expect to obtain, a first or upper second-class honours degree or equivalent in an appropriate subject from a recognised academic institution. Candidates must fulfil College admissions criteria.

 Some experience in in vivo work would be an advantage including in vivo imaging. Holding an animal license would be an added advantage.

How to Apply

To apply, please email Jaya Rajamanie ([Email Address Removed]) with the following documents.

-      Your CV

-      The names and addresses of at least two academic referees.

-      A personal statement of no more than 1,000 words explaining your interest in the project and ensure that you specify your degree classification for your undergraduate and postgraduate degrees (and attach scanned copies of the certificates if possible).

Selected candidates will get a tour of the relevant campus. Please assume that your application has not been successful if you have not heard from us within a month of the closing date.

Closing date for all applications: 20 February 2023

Interviews will be held online mid/end of March.