Dr Mike Tomlinson

Supervisor Details

Contact Details

Scientific Background

Research Interests

Mike鈥檚 research focuses on tetraspanin membrane proteins as potential therapeutic targets for major human diseases such as cancer, cardiovascular and inflammatory diseases. He enjoys research-led teaching on the molecular mechanisms underlying these diseases.

Mike鈥檚 group investigates how tetraspanins regulate other important membrane proteins on the surface of human cells.

Mike has recently established a new paradigm in human membrane protein biology, whereby the important cell surface 鈥榤olecular scissor鈥� ADAM10 is not one scissor, but six different scissors depending on which one of six tetraspanins, termed the TspanC8s, it is associated with 鈥� his 鈥榮ix scissor鈥� hypothesis. This has major implications for future therapeutic targeting of diseases such as cancer, Alzheimer鈥檚 disease, asthma and inflammatory diseases including those leading to heart attack and stroke. Targeting all six ADAM10 scissors in these diseases would be too toxic for the patient, but targeting the one scissor that is causing the disease has great potential.

Mike has also identified tetraspanin Tspan18 as a critical regulator of the store-operated Ca²⁺entry channel Orai1 on endothelial cells, and as a potential therapeutic target for thrombo-inflammatory diseases such as deep vein thrombosis.

Scientific Inspiration

Professor Alan Williams (1945-1992), FRS, Head of the MRC Cellular Immunology Unit and Sir William Dunn School of Pathology in Oxford. My supervisor at the start of my PhD. Inspired me to work on cell surface proteins.

Research Groups

Supervision Style

In three words or phrases: Laid-back, collaborative, teaching.

Provision of Training

Your training will be supervised by me or by my experienced post docs/PhD students, leading to more independence later.

Progression Monitoring and Management

I will expect you to take full ownership of your progression but come to me when you need help troubleshooting.

Communication

I am known to email my team at all hours of the day and night - I have four kids and need to work flexibly. However I will not expect you to do the same - a good work/life balance is important.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once per week

In year 1 of PhD study

At least once per week

In year 2 of PhD study

At least once per fortnight

In year 3 of PhD study

At least once per fortnight

The meetings will be face to face and I am usually contactable for an instant response (if required) on every working day.

Working Pattern

The timing of work in my lab is flexible and I expect students to manage their own time, although there will be occasions when they are being shown techniques or working as a team, when they will need to adapt to the working times of others.

Notice Period for Feedback

I need at least 1 week鈥檚 notice to provide feedback on written work of up to 5000 words.

MIBTP Project Details

Primary supervisor for:

Investigating the structure and function of tetraspanin membrane proteins

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).

Investigating the structure and function of tetraspanin membrane proteins

Secondary Supervisor(s): Prof Tim Knowles

University of Registration: University of Birmingham

BBSRC Research Themes: Understanding the Rules of Life (Structural Biology)

Project Outline

Tetraspanin membrane proteins are emerging as potential therapeutic targets for major human disorders such as cancer, infection and inflammatory diseases. Tetraspanins function by interacting with and regulating other membrane proteins including proteases, ion channels and adhesion proteins. There are 33 tetraspanins in humans but many remain functionally uncharacterised. Nevertheless, experiments in tetraspanin knockout mice, cultured cells, and genome-wide association studies, are revealing tetraspanin links to human disease. Moreover, cryo-electron microscopy (cryo-EM) studies are beginning to provide a mechanistic understanding of tetraspanin structure and function.

The objectives of the project are as follows:

鈼� To identify novel tetraspanin interaction partners using lipid nanodisc technology, proximity biotinylation and mass spectrometry proteomics.

鈼� To investigate how tetraspanins regulate their identified partners using CRISPR/Cas9 knockout of the tetraspanins and functional assays in cultured cells.

鈼� To gain structural information on tetraspanin complexes with partner proteins in lipid nanodiscs using cryo-EM.

The impact of the project will be the identification of novel mechanisms by which tetraspanins regulate cell function, thus enabling future translational work on tetraspanins as drug targets in human disease.

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Midlands Integrative Biosciences Training Partnership