New biomedical PhD funding, T cell receptors (Chris Ponting)

New biomedical research PhD launched in Scotland
https://www.actionforme.org.uk/news/new-biomedical-research-phd-launched-in-scotland/

Action for M.E. and the Scottish Government’s Chief Scientist’s Office are delighted to announce the recipient of our jointly funded PhD studentship in biomedical M.E. research.

Prof Ponting will supervise a PhD student who will use samples drawn from the UK M.E. Biobank to investigate whether people with M.E. differ in their T-cell repertoire from healthy controls. This is important because such differences could indicate an ongoing response to infection or autoimmunity.

The student will also engage directly with people affected by M.E., including blogger and advocate Simon McGrath, and the UK CFS/M.E. Research Collaborative, of which Prof Ponting is Deputy Chair.

Prof Chris Ponting says: “We are thrilled with this award because it will allow us to pursue research into this devastating condition. The technology that we wish to use would be an extension to what others have done previously and, importantly, it would be cheaper. We hope – once the technology is established – to generate new hypotheses that may eventually reveal causes and affordable diagnostic tests for some across the M.E. spectrum.”

read on
https://www.actionforme.org.uk/news/new-biomedical-research-phd-launched-in-scotland/

Note that is aiming to replicate/expand on Mark Davis's work at Stanford that found striking evidence of T cell clonal expansion, work that is now being funded by @OMF

My blog on this from last year:
Mark Davis finds the strongest evidence yet for ME/CFS immune activation and hunts for the trigger

 

This is very exciting! I like Chris more and more, and I'm usually quite sceptical!

 

This is great news @Simon M
A big thankyou to you and especially Chris! I think this could be be game changer in the UK.
Prof Ponting is quite specialised in this area of work isn’t he?

 

This is good news. Many thanks for your involvement Simon, and particularly for the influence you’ve had on Chris Ponting. The more I hear from him, the more confidence I have in him.

I am reminded of Simon Wessely’s quote:
“a litle more psychology and a litle less T cells swould be welcome.”
(http://www.simonwessely.com/Downloads/Publications/CFS/3.pdf)

 

A bit of background

Me too. The study came about after I mentioned Mark Davis's work on T cells to Chris. I thought that was one of the most promising findings I'd ever seen. From my blog on the work:


Look at that difference!

Chris also thought it was exciting and important. I hadn't expected him to launch a research project about it, though. By an extreme stroke of good luck, Chris was part of a consortium at Wellcome Sanger Institue (https://www.sanger.ac.uk/) ;looking to find a cheaper way to sequence T cell receptors. Sequencing these is at the heart of MArk Davis's work and this study too, the new techniques being developed at Sanger and as part of this project should allow it to be done faster and much cheaper, allowing bigger samples and more cells per patient.

The technique is being developed by Dr Lia Chappell at Sanger and will be implemented further by the PhD candidate at Chris's lab in Edinburgh

More on this when I have more energy.

Love it. I don't think Simon W was ever very keen on the patient perspective on research.

 

Great news!

 

Well, hasn’t that just brightened my day!

 

The biology behind the study

The aim of the PhD is to build on Mark Davis's work, which indicated that for mecfs the problem with the immune system could be T-cell clonal expansion.

T cells are cousins of antibody producing B cells. And just as antibodies have very specific binding, so too do receptors of T cells called, yes, T cell receptors (TCRs). When a T cell receptor finds a "match", by binding to a very specific antigen, the T cell is stimulated to start clonal expansion. This is where one cell divides to form two identical twins, that have identical TCRs. Each twin then divides again and so on until there is a small army of identical clones.

Mark Davis's study was mainly looking at T cell clonal expansion in healthy people vs oseveral diseases, including Multiple Sclerosis and acute Lyme disease. At the last minute, he won a grant to include ME/CFS patient samples as well, and found that these also have clonal expansion similar to that seen in several diseases.

But how do you measure clonal expansion? All cells in a clone have identical TCRs so the only way to be sure of how many places you have is to laboriously sequence the T cell receptor of every T-cell, and count the matches. If you have a lot of matches then you have clonal expansion. This is exactly what you are seeing in Mark Davis’s data below, where the numbers refer to…

Davis did this for six ME/CFS patients.



Note that this work uses about 300 cells from each of the six patients. It is expensive work because you have to sequence each cell separately, hence the small samples.

Graph inc other diseases:


The new PhD project will use similar technology but develop it further in order to dramatically lower costs, allowing much bigger samples. The goal is to sequence TCRs for 10,000 cells per patient and for many more patients. The initial target is 50 patients and 50 controls but the ambition is to eventually do it for all samples in the UK ME/CFS biobank, and possibly for other cohorts as well.

Of course, the original idea came from Mark Davies who is a brilliant immunologist. Judging by a video of his I watched, he was doing this work to try to find early signs of illness in people who appear healthy. He is a T cell receptor expert and that's presumably why he focused on TCRs.

I want to thank Action for ME and the Scottish Government’s Chief Scientist’s Office for funding this work, which I think is incredibly important. Replication is central to establishing robust results, and I can't think of a more important finding to try to replicate than T cell clonal expansion. The PhD is also trying to take things further by reducing costs and using much larger samples. Plus, this will introduce a new researcher at the start of their career to mecfs, and at a top lab.

 

It' s so satisfying to see biomedical research being funded by Scottish government .

We have great university and biosciences expertise in Scotland which could be a huge advantage.

It' s usually focused on heart diseases , diabetes and cancer , so great to see ME widening this interest ( perhaps even more valuable as similarities with cancer and diabetes have been noted )

 

Also genetics - the land of Dolly the sheep

 

@Simon M Thanks so much for this explanation. Does the T cell clonal expansion play a role in non-Hodgkins lymphoma do you know? Several people in my family have had Non-Hodgkin's and it is also more common in people with ME so I feel there's a connection for me, I'm always curious to know what that connection might be. Just wondering!

 

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