Professor Steve Watson

Supervisor Details

Contact Details

Professor Stephen Paul Watson

Supervisor Department, Supervisor University

Scientific Background

Research Interests

My research seeks to understand the molecular basis of activation of platelets by the four glycoprotein receptors, GPVI, CLEC-2, FcγRIIA and PEAR1, through Src and Syk tyrosine kinases. We study the events that lead to clustering and downstream signalling using single molecule localisation microscopy, molecular modelling and structural studies.

Scientific Inspiration

I trained in Pharmacology at the University of Leeds and was inspired by the lectures on the mechanism of activation of cell surface receptors.

Research Groups

Birmingham Platelet Group

Supervision Style

In three words or phrases: inclusive, student-focussed, collaborative.

Provision of Training

From the beginning, you will be taught the laboratory skills from a research fellow, Alex Slater, and be involved in almost daily meetings with myself and Alex until you have settled. From then on the supervision will be tailored to give you independence but in the knowledge that there is always support available.

Progression Monitoring and Management

We will have a formal meeting every week to establish progress, but either Alex or I will be available almost every day to provide advice and guidance. We aim to give you the self-confidence to design your experiments and follow your ideas, while retaining realistic goals.

Communication

I am available nearly all hours of the day but would not expect you to be the same and respect this. We have a weekly lab meeting at which you will present approx. 3 times per year. You will be part of a group of 25 - 30 people which 10 supervisors with the philosophy that everyone can provide help.

Meetings

PhD Students can expect scheduled meetings with me at least once per week. These meetings will be face-to-face. I am usually contactable for an instant response on every working day.

Work Patterns

The timing of work in my lab is completely flexible, and (other than attending pre-arranged meetings), I expect students to manage their own time.

Notice Period for Feedback

I need at least 1 week's notice to provide feedback on written work of up to 5,000 words.

MIBTP Project Details

Primary supervisor for:

The role of O-glycosylation of the stalk region of the immunoglobulin receptor GPVI

See the PhD Opportunities section to see if this project is currently open for applications via MIBTP.

Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).

The role of O-glycosylation of the stalk region of the immunoglobulin receptor GPVI

Secondary Supervisor(s): Dr Alex Slater

University of Registration: University of Birmingham

BBSRC Research Themes:

Understanding the Rules of Life (Structural Biology)

Project Outline

The platelet collagen receptor glycoprotein VI (GPVI) is a target for a new class of antithrombotic drug. GPVI is a single transmembrane receptor with two extracellular immunoglobulin domains, an O-glycosylated stalk, and a short intracellular tail.3 O-glycosylation accounts for 50 % of the molecular weight of the receptor. A monoclonal antibody to the glycosylated stalk is a potent inhibitor of collagen signalling.

We aim to map the sites of O-glycosylation and determine the function of this region using 3 work packages:

WP1: Mapping sites of O-glycosylation.

Serine/threonine residues in the GPVI stalk region will be individually mutated and the constructs expressed in human embryonic kidney cells. Loss of O-glycosylation will lead to a reduction in molecular weight by mass-spec and SDS PAGE. Further mutants lacking two or more sites will be made in an iterative manner to generate a O-glycosylation-deficient form of GPVI. We will use super-resolution microscopy to monitor the effect of glycosylation on the distribution of eGFP-labelled GPVI.

WP2: Determine the functional roles of GPVI glycosylation in receptor expression and signalling.

The effect of loss of O-glycosylation on expression and function of GPVI will be studied in a DT40 B cell line as these express the machinery to support signalling. The expression of GPVI will be measured by flow cytometry and signalling in response to GPVI-specific ligands will be measured using a Nuclear Factor of Activated T Cells (NFAT) transcription reporter assay.

WP3: Using nanobodies to probe glycosylation function.

We will raise nanobodies against the stalk region using the recombinant GPVI stalk through the VIB Nanobody Core. We will characterise the ability of the nanobodies to bind wild type GPVI and the glycosylation mutants. The effects of the nanobodies on expression and signalling of GPVI in the transfected cell lines and on platelets will be investigated.

APPLY HERE