Manuscript selected for ‘In this issue’ – European Journal of Immunology

Posted: 27 November 2009

Congratulations to Dr Claudia Kemper, whose paper, ‘CD46-induced human T reg enhance B-cell responses’ has been selected for this month’s ‘In this issue’ section of the European Journal of Immunology. The paper, written by Anja Fuchs, John P. Atkinson, Veronique Fremeaux-Bacchi and Claudia Kemper, looks at the effect of Complement (CD46)-induced T regs, called cTreg, on B-cell functions. The authors demonstrate that cTregs induce an enhanced B-cell activation and promote an increased Ig production through IL10 secretion and yet unknown cell contact-mediated mechanism. Moreover, Fuchs et al show that T cells from a CD46-deficient patient failed to induce B cell activation. These findings might explain why some CD46-deficient individuals develop common variable immunodeficiency (CVID).

See the abstract and download a full PDF on the Wiley Online Library.

Tissue and tolerance – patient involvement in biomarker studies

Posted: 7 November 2009

by William Gage

Research using tissue taken from patients is central to increasing the understanding of disease and to developing new and improved diagnostics & treatment. The translational research undertaken in the MRC Centre for Transplantation is no exception, with numerous studies depending on human tissue taken from patients attending the wards and clinics at Guy’s & St Thomas’.

However, recent years have witnessed several high-profile controversies surrounding the use and retention of human material. The Human Tissue Act which came into place in 2004 is the first UK legislation to explicitly require consent for use of human tissue for research. Therefore an important part of my role as a clinical research nurse is to facilitate this process in the recruitment of renal transplant patients to studies in the ‘Biomarkers of Immunological Tolerance’ project, led by Dr Maria Hernandez-Fuentes. Successfully identifying patients with biomarkers of tolerance could enable clinicians to reduce immunosuppressive drugs for these patients earlier.

More often than not, individuals who have received a transplanted kidney are themselves expert in renal disease and are usually more than happy to participate in research by donating samples. Renal disease is debilitating to live with and post-transplant immunosuppressive drug regimes can have serious side-effects which significantly impact on an individual’s life. Any discovery which may reduce the need for patients to take these drugs is viewed very positively by patients. Similarly, those ‘living-donors’ who have given one of their kidneys to a friend or relative are also usually very willing to help by donating their tissue samples for the research.

There are statutory and ethical regulations to consider when asking patients to think about donating tissue samples; they need to have been given sufficient information to ensure that they are making a fully informed decision, they must have enough time to think about their decision and they must be reassured that they can withdraw from the study at any point if they change their mind. Individuals often have a number of questions before they agree such as what kind of research their tissue will be used for, how it will be stored and disposed of, what information researchers will have access to, will they get to know about the results of the research and – ultimately - will it directly affect their treatment.

When patients donate tissue they are giving us a gift – so the issues that are important to participants should also be issues which are important to us as clinicians and researchers.

MRC Centre for Transplantation celebrates its second birthday with new appointments

Posted: 30 September 2009

Two years into its research programme the MRC Centre for Transplantation is happy to announce three new appointments to further extend its research portfolio.

Professor Randy Noelle joins the Centre from Dartmouth Medical School, New Hampshire. Professor Noelle’s research focuses on immunology and his laboratory in Dartmouth identified a novel membrane protein expressed on helper T lymphocytes. The protein and its receptor play a central role in antibody and cell mediated immunity. Intervention in this interaction can block a wide range of immune and autoimmune responses as well as transplant rejection. The new Professor of Transplant Science and Immunotherapy hopes to develop collaborative research in a number of areas including immune tolerance in transplantation and the exciting area of cancer vaccines.

A further two new roles will take forward the translational arm of the MRC Centre and link in strongly with the NIHR Biomedical Research Centre. Professor Anthony Dorling joins from Imperial College London and brings with him an active programme of research in the field of coagulation. His work focuses on the influence and importance of coagulation proteins on immune activation and adaptive responses particularly in the context of transplant rejection. Professor Prokar Dasgupta, Chair in Robotic Surgery and Urological Innovation, is a clinician scientist currently based at Guy’s and St Thomas’ NHS Trust. He will develop a new arm of academic research into the groundbreaking field of robotic surgery. His laboratory interests are in receptor biology of the lower urinary tract.

Centre Director Professor Steve Sacks commented ‘These three exciting appointments will further expand the strength and breadth of research expertise within the MRC Centre for Transplantation. As we celebrate our 2nd Birthday we can look forward to exciting research developments in these new fields of investigation’.

Centre PhD student wins best oral presentation prize

Posted: 30 September 2009

John Cardone, 2nd Year PhD student at the MRC Centre for Transplantation, won an award this month at the 12th European Meeting on Complement and Human Disease in Hungary for his presentation: ‘CD46: A molecular switch between effector and regulator T cell response?’


On winning the award for best oral presentation of the session, John said “my PhD project is based on a recently described type of complement activated T-regs (cTregs). The main focus is to understand the triggers and signalling pathways involved in the induction of such cTregs. Identifying when and in response to which stimuli cTregs produce IL-10 -an immunosuppressive cytokine-will enable us to study approaches to prevent graft rejection and autoimmune diseases.” You can see an abstract of the presentation on the Science Direct website.

John was also awarded a travel bursary.

PhD students survive first year

Posted: 21 July 2009

“The supervision and facilities here are brilliant” says Adam Laing when we ask him and his fellow 1st year MRC Centre for Transplantation PhD students to tell us about their first year experiences.

Visitor attractions
“I was surprised by the amount of high profile people giving talks at the Centre about real cutting-edge research, allowing us to network with internationally recognised experts” says Niwa Ali. “It has been exciting to follow lectures from world leading scientists, including Abul Abbas, Martin Birchall and Anne O’Garra, that I believe not every institution has the pleasure to host” adds John Cardone.

Teaching
“The teaching sessions were very useful” says Jennifer Mollon, “The topic selection must have been challenging with such a varied group, but the organisers did an excellent job.” John agrees “…journal clubs, internal lectures and lab meetings helped us to understand in more detail how to approach science, how to develop a critical eye and how to present our own research.”

First night nerves
“There was a small worry in my mind when I started” says Jennifer, “the centre was new, would they know how things work, would I be an important part of it? There was no need to worry! The enthusiastic and dedicated Centre team continue to ensure that everything goes smoothly.” Niwa envisaged a real struggle with his project’s mouse work “as I did not have any prior experience in animal work. However, the MRC Centre has an abundance of people that are highly experienced in these areas and were always available to provide crucial support and guidance whenever required.”

Challenging
Like all the students, Ehsan Sharif-Paghaleh found his first year a challenge “…experiments were not always successful. However, this helped me improve my problem solving skills. My project is multidisciplinary and ranges from molecular biology to immunology, transplantation and imaging. This has given me a great opportunity to improve my skills in various fields of science.” Jennifer, as a statistician, had little background knowledge in biological science. “I've had to quickly get to grips with key ideas in genetics, transplantation and immunology. Though the work is very challenging things [are] proceeding well and I am starting to see the way forward to a positive outcome in a few years' time - something that wasn't so easy to see at the start!”

Making their mark
Already though, our 1st years are on the international stage. Ehsan had an abstract accepted for a poster presentation at the European Congress of Immunity 2009 and John has been invited to give a presentation at the Complement in Human Diseases Congress in Hungary this September. “No doubt without a high quality lab, supervisor and colleagues I would not have been invited”

We're havin' a good time
“The wine-tasting evening was a fantastic introduction” says Jennifer. “The Centre is a brilliant place to work…everyone has been very friendly and encouraging” says Adam. “my first year … [has been] one of the most enjoyable and challenging things I have ever done in my life. “ says Ehsan. Not to be outdone, Niwa concludes “Overall, the experience has been fantastic and I feel as though I have become a much better and more competent scientist in the past year, not only in the lab but also at communicating my science through presentations and lab meeting discussions with peers. I really do believe that the MRC Centre is definitely the place to be right now!”

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