BBSRC CASE PhD in Infection and Immunity: Dissecting the relationship between phosphinositide3-kinase δ activity and L-selectin expression by leucocytes

Outline

The PhD position will be funded through a BBSRC ICASE Studentship with GlaxoSmithKline (GSK).

This project is based on the new concept that L-selectin expression is required for influenza virus clearance by cytotoxic T lymphocytes (CTLs). Since the inhibition of phosphinositide-3-kinase δ (PI3Kδ) is known to result in the overall increase of cell surface expression of L-selectin in CTLs and other types of leucocytes (1, 2), we propose to study the potential pathways linking PI3Kδ inhibition and L-selectin expression in host immune responses against viral infections.

The leucocyte restricted homing molecule L-selectin has not been considered an important molecule on influenza-specific CTLs since expression is downregulated following T cell activation and is low on CTLs harvested from infected lungs. However, Dr Ager has shown that L-selectin is re-expressed on influenza-specific CTLs before lymph node egress and L-selectin is essential for virus clearance since L-selectin null CTLs cannot control influenza infection despite being activated in lymph nodes. Moreover, L-selectin enhanced CTLs expressing a shedding-resistant mutant of L-selectin, which do not downregulate L-selectin following activation (LΔP) are superior in controlling influenza infection.

The classical view of the role of L-selectin in T lymphocyte homing was restricted to naïve and central memory trafficking to lymph nodes; however, Dr Ager’s new data has overthrown this dogma. We have shown that CD8+ T cell dependent clearance of pulmonary influenza infection is limited by the level of L-selectin expressed on early stage effector T cells and maintaining high L-selectin levels improves virus clearance.

This proposal aims to determine the interplay between PI3Kδ and L-selectin in leucocytes during virus infections of the lung.

What is funded

Full UK/EU tuition fees

If applicable, any eligible non-home fee paying candidate must fund the remainder of the overseas fee themselves.

Duration

4 years with a minimum of 3 months at industrial partner (GSK)

Eligibility

Open to all UK/EU students without further restrictions

You will hold or expect to achieve a First or Upper Second Class degree in a relevant area (e.g. natural sciences, biomedical sciences, immunology, biochemistry). As this is a training doctorate, previous research experience is not essential.