Members

Sir William Dunn School of Pathology

University of Oxford

T Cell Signalling Group

Principal Investigator

Professor Oreste Acuto, Ph.D.

Oreste Acuto studied Biology at the University of Rome where he obtained a Doctorate degree in Immunology. He then spent two years at the Department of Biochemistry in the Swiss Institute of Technology (ETH) in Zürich and three years at the Swiss Institute of Cancer Research in Lausanne studying the biochemistry and function of membrane proteins and immunoreceptors, respectively. He then moved to the Dana-Farber Cancer Institute at the Harvard Medical School where he worked from 1982 to 1988 at the initial identification, biochemistry, molecular cloning and functional characterization of the T-cell receptor in Ellis Reinherz's laboratory. In 1988, he became Director of the Molecular Immunology Unit at the Pasteur Institute, Paris, where he has been studying the molecular basis of T-cell recognition of foreign antigens and activation mechanisms. He moved with his laboratory to the University of Oxford in 2006 and is now Professor and Senior Research Fellow at Sir William Dunn School of Pathology.

Tel: 0044 (0)1865 275615

Email: oreste.acuto@path.ox.ac.uk

Postdoctoral Researchers

Konstantina Nika, Ph.D.

I completed my Ph.D. at Portsmouth University in 2001 and did 4-years post-doctoral training in the USA with Prof. Tomas Mustelin, at the Burnham Institute in San Diego. I joined Professor Acuto’s laboratory in August 2006.

I am interested in studying the molecular events that direct the initiation of T cell signalling. Currently, my investigation involves understanding quantitative and qualitative aspects of active and inactive isoforms of the Src-family kinase Lck and its distribution in resting and activated T cells.

Tel: 0044 (0)1865 285755

Email: konstantina.nika@path.ox.ac.uk

Tel: 0044 (0)1865 285755

Email: mogjib.salek@path.ox.ac.uk

Tel: 0044 (0)1865 275526

Email: wolfgang.paster@path.ox.ac.uk

Technical assistance

Adrian Gray
(Laboratory manager/technician)

Having gained my BSc in Biochemistry from the University of Kent in 1993, I spent three years working on Salmonella infections in poultry.
I then joined the MRC Anatomical Neuropharmacology Unit in Oxford where I spent eight years providing technical assistance to a lab investigating receptors in the central nervous system.

I joined the Acuto lab in January 2008 as a laboratory manager and technician. In addition I am assisting Konstantina with her project.

Oxford University Webpage

Dunn School Webpage

Mogjiborahman Salek, Ph.D.

After my Diploma thesis in France (IPBS/Toulouse), I completed my PhD thesis with Prof. Wolf Dieter Lehmann at the University of Heidelberg (DKFZ-Heidelberg/Germany). In July 2006, after a post-doc in the Proteomics Group of Dr. Juri Rappsilber (IFOM-IEO, Milan/Italy), I joined the newly settled group of Prof. Oreste Acuto. Since my PhD I have worked on the analysis of protein posttranslational modifications by MS and their biological implications.

My present interest is, by using state-of-the-art proteomics, to investigate quali-tative and quantitative changes of the T cell proteome induced upon activation. I am also adviser of the Central Proteomics Facility.

Wolfgang Paster, Ph.D.

After receiving my diploma in Molecular Biology from the University of Vienna in 2002, I joined the lab of Prof. Hannes Stockinger at the Medical University of Vienna for my PhD thesis. We were mainly interested in proximal T cell receptor signaling, particularly focusing on the Src-family kinase Lck by live cell imaging techniques (FRET and FLIM-imaging) as well as biochemical methods. After finishing my thesis, I continued in Prof Stockingers laboratory as a postdoctoral fellow until I joined the lab of Prof. Acuto in April 2008.
My current research focus is on the buildup of the early T cell receptor signaling complex upon TCR engagement using high affinity protein tags and quantitative proteomics. In particular, I aim to shed light on the still poorly understood regulatory mechanisms around Lck. I want to create a time-resolved map of the Lck interactome ultimately leading to defined molecular stoichiometries of key signaling molecules. The project is carried out in close collaboration with Dina and Mogjib.

Tel: 0044 (0)1865 285755

Email: adrian.gray@path.ox.ac.uk

DPhil students

Vincent Geoghegan
(3rd year, Keble College)

After completing a master of biochemistry degree at St-Hugh’s College, Oxford in June 2008, I joined Professor Acuto’s group in July 2008 to begin my DPhil degree.

I am examining the role of arginine methylation in T-lymphocyte activation. We have developed proteome-wide methods for the identification of arginine methylated proteins in T-lymphocytes.

Using these methods, I have discovered several arginine methylated proteins important for T-lymphocyte activation. I will examine the role that arginine methylation plays in the function of these proteins.

Tel: 0044 (0)1865 275526

Email: vincent.geoghegan@path.ox.ac.uk

Tel: 0044 (0)1865 285755

Email: annika.bruger@path.ox.ac.uk

Tel: 0044 (0)1865 285755

Email: david.pepper@path.ox.ac.uk

David Pepper
(Research assistant)

After graduating in Zoology from Reading in 2001 I spent 3 years working in analytical parasitology, most notably on cryptosporidium parvum.
After this point I moved back to the University of Reading as a Research Assistant in the Molecular Endocrinology department of AMS. The following 4 years were spent undertaking a variety of research projects involving N-terminal pro-opiomelanocortin peptides and their effects on adrenal proliferation, steroidogenesis and developmental differentiation.
I currently work in the Acuto lab as a Research Assistant on an EU funded grant provided to investigate the activation of previously undiscovered protein kinase cascades promoted by T-cell antigen recognition.

Tel: 0044 (0)1865 285755

Email: andrew.howden@path.ox.ac.uk

Andrew Howden, Ph.D.

I completed my undergraduate degree in plant science at the University of Edinburgh and the University of California, Davis. I moved to Oxford in 2003 and completed my D.Phil. in plant-microbe interactions.
I am especially interested in cell signalling and stress, and during my postdoctoral work with Dr Lee Sweetlove in Oxford I used phosphoproteomic techniques to examine how plants respond to stress in their environment.
I joined Professor Acuto’s lab in June 2010 to complete a short project to identify changes in the proteome of activated primary T-cells using SILAC and LC-MS.

Tel: 0044 (0)1865 285755

Email: rebecca.taylor@path.ox.ac.uk

Tel: 0044 (0)1865 285755

Email: ben.dewet@path.ox.ac.uk

Ben de Wet, Ph.D.

I obtained a Ph.D. in Microbiology from the University of Stellenbosch in South Africa, and subsequently moved to the laboratory of Siamon Gordon at the Sir William Dunn School of Pathology at Oxford to study the interactions between innate pattern recognition receptors and pathogens.

This was followed by a period in the laboratory of Thomas Harder, also at the Dunn School, investigating the formation of signaling complexes in activated T cells by quantitative mass spectrometry.

I am currently involved with further studies on the stoichiometry and quantitative characterization of isolated T cell signaling complexes.

Rebecca Taylor
(1st year, Lincoln College)

Having graduated from the University of Manchester with a Bachelors in Biomedical Sciences, I joined the Professor Acuto’s group in October 2010 to begin my DPhil degree.

The protein THEMIS, a previously unknown component of signalling pathways downstream from the TCR, was identified by the Acuto group in 2009.
I am interested in the function of THEMIS and what role it plays in regulating T cell development and signalling. My DPhil will involve the use of biochemical techniques to identify the role of THEMIS in key signalling events following TCR stimulation.

Annika Målin Bruger
(2nd year, Lincoln College)

I joined the Acuto lab to start my thesis in October 2009 after graduating with a Master of Biochemistry from the University of Bath. I’m under co-supervision of Professor Oreste Acuto and Dr. Simon Hunt and am in collaboration with UCB in Slough.

I am interested in studying how TCR signals of varying strengths are transduced intracellularly.
To achieve this I use cells expressing the 1G4 TCR which recognises a melanoma-derived antigen peptide. Variations of the peptide are used to study the reactions of T cells to antigens of different affinities. In particular I am interested in the differences in phosphorylation of key signalling molecules downstream of the TCR.