Professor Martin Dyer

Supervisor Details

Contact Details

Scientific Background

Research Interests

Martin Dyer is an academic clinical haematologist and Director of the Ernest and Helen Scott Haematological Research Institute (EHSHRI) at Leicester Cancer Research Centre. He specialises in experimental therapies for lymphoid malignancies. His track record includes both clinical and laboratory studies on CAMPATH/alemtuzumab and obinutuzumab antibodies and precision medicines including the BCL2 inhibitor venetoclax and BTK inhibitor, tirabrutinib. By combining early-phase clinical studies with laboratory investigations, his team has defined mechanisms of inherent and acquired resistance and identified novel pathways in lymphocyte transformation using proteomics studies and molecular cloning of chromosomal translocations targeting the immunoglobulin loci. Through the Leicester Haematological Malignancy tissue bank, he has contributed to several national GWAS studies investigating genetic predispositions of chronic lymphocytic leukaemia.

Scientific Inspiration

Too many to mention but like people who 鈥淪ee things not as they are, but as they might be".

Supervision Style

In three words or phrases: Very supportive, inclusive, collaborative.

Provision of Training

My lab consistently provides a very welcoming and supportive environment. I will seek to support you throughout all the different phases of your PhD and the difficulties, problems (and successes) you will encounter.

Progression Monitoring and Management

I will seek to guide and advise you to establish goals. Like all PI鈥檚 I like to be kept up to date with what is happening! We will discuss questions, data, experimental design etc in both 1:1 and lab meetings to ensure you progress and to help troubleshoot problems.

Communication

We have a lab WhatsApp group which allows for announcements, direct messages, sharing papers, coordinating lab operations, arranging meals and so on! I will regularly contact lab members through emails, face-to-face or remote meetings. There are weekly lab meetings to discuss progress, but I will also meet (usually F2F) with PhD students on a weekly basis. However I am always contactable.

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 (if required) 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鈥檚 notice to provide feedback on written work of up to 5000 words.

MIBTP Project Details

Primary supervisor for:

Decoding How Therapeutic Antibodies Remodel Lymphocyte Membranes: A Biophysical Approach to Immune Cell Function

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).

Decoding How Therapeutic Antibodies Remodel Lymphocyte Membranes: A Biophysical Approach to Immune Cell Function

Secondary Supervisor(s): Professor Andrew Hudson, Professor Karl Ryder, Dr Harriet Walter

University of Registration: University of Leicester

BBSRC Research Themes:

Understanding the Rules of Life (Immunology)

Project Outline

Therapeutic monoclonal antibodies (MAbs) targeting B cell surface antigens have revolutionised treatment of autoimmune diseases including rheumatoid arthritis, neurological disorders such as multiple sclerosis, and B cell malignancies including lymphoma and chronic lymphocytic leukaemia. CD20 antibodies, such as rituximab, obinutuzumab and ofatumumab have delivered major improvements in patient outcomes.

Despite this success, both the physiological function of CD20 and the precise mechanisms of action of CD20 MAbs remain incompletely understood. CD20 MAbs are pleiotropic and can induce antibody dependent cellular cytotoxicity, activate complement, induce apoptosis and cell cycle arrest, B cell polarisation and homotypic cellular aggregation. Which of these mechanisms are critical for B cell depletion in vivo remains uncertain.

We have observed that some therapeutic MAbs induce a novel form of in vitro B-cell depletion. B cells labelled with specific MAbs are depleted on passing through the fluidics of flow cytometers. This process is rapid (occurring in <15mins), dependent on the precise epitope recognised by the MAb, antigen density, on temperature and the presence of divalent metal ions, and is not suppressed by inhibitors of forms of programmed cell death.

Our hypothesis is that some MAbs rapidly induce changes at the lymphocyte plasma membrane resulting in cell lysis under conditions of fluidic stress; the biological basis of this mechanism is unknown.

We propose a series of detailed biophysical investigations to study the consequences of antigen/antibody interactions at the cell surface membrane of well-characterised B cell lines.

In particular, the research will take advantage of new transformative technology for single molecule force measurements 鈥� an apparatus called the Lumicks C Trap which combines optical-force tweezers with microfluidics and confocal imaging. Additional imaging modalities will include atomic force and cryo-electron microscopy.

Co-supervisor on projects with Dr Harvinder Virk and Dr Robert Britton.

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Midlands Integrative Biosciences Training Partnership