PhD Studentship â Improving immunotherapy for Alzheimerâs Disease by engineering antibodies. (1028318BJ)

PhD Supervisors: Jessica Teeling and Nullin Divecha; Co supervisors/sponsor: Allan Jensen (Lundbeck)

Interviews will be held: tbc

PhD Description:  

Many elderly will develop Alzheimer’s Disease (AD) but poor understanding of the underlying disease mechanism has hampered development of drugs. Immunotherapy to remove amyloid plaques from the brain showed very promising results in the laboratory. Unfortunately, clinical trials were less successful due to side effects. The brain requires a balanced immune system to prevent overreaction and too much, but also too little, activation may result in damage to the AD affected brain.  A number of cell surface receptors play a role in immune regulation, including receptors that bind to antibodies, called Fc Receptors (FcRs). We have shown increased expression of FcRs in aged and AD-affected brain, and they may contribute to neuroinflammation after binding to therapeutic antibodies.  The crystal structure of FcRs has allowed identification of the precise antibody binding sites and this information can be used to engineer antibodies with different properties. We propose to generate amyloid-specific antibodies with different effector function and binding characteristics to FcR. The student will test these antibodies in cell cultures in vitro or in vivo and measure the effects on amyloid removal, cell signalling, neuroinflammation and behavioural tasks (eg memory). We predict that this PhD-project will provide evidence that antibodies with altered binding or signalling through FcRs are safer and more effective drugs

This PhD studentship is a collaborative project between The University of Southampton and Lundbeck, who are based in Denmark. We are looking for a highly motivated candidate who will benefit from training in a range of molecular, biochemical, in vivo and ex vivo techniques.

The project is funded for 3 years and welcomes applicants from the UK and EU who have or expect to obtain at least an upper second class degree in Biological Sciences or allied subjects. Funding will cover fees and a stipend at current research council rates of £ 14,777 per annum for 2018/19.  Due to funding restrictions this position is only open to UK/EU applicants.

Relevant literature: 

Comparing the efficacy and neuroinflammatory potential of three anti-abeta antibodies.

Fuller JP, Stavenhagen JB, Christensen S, Kartberg F, Glennie MJ, Teeling JL.

Acta Neuropathol. 2015 Nov;130(5):699-711. doi: 10.1007/s00401-015-1484-2. 

Antibody Engineering for Optimized Immunotherapy in Alzheimer's Disease. Isabelle L. Sumner, Ross A. Edwards, Ayodeji A. Asuni and Jessica L. Teeling. Front Neurosci. 2018; 12: 254. doi:10.3389/fnins.2018.00254

Applications for an MPhil/PhD in Biological Sciences should be submitted online at:

https://studentrecords.soton.ac.uk/BNNRPROD/bzsksrch.P_Login?pos=4973&majr=4973&term=201819  Please place Jessica Teeling in the field for proposed supervisor.

General enquiries should be made to Jessica Teeling at 

jt8@soton.ac.uk.  Any queries on the application process should be made to pgafnes@soton.ac.uk

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, 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.

Closing Date: 26 Jul 2018
Post Type: PhD Studentship (Funded)