Graduate Research Prize Winners 2011
After completely failing to secure a position in any Medical School at Portugal, I decided to do Biochemistry at Faculty of Sciences of University of Porto, which turned out to be a good decision. The course was run by fantastic professors in an atmosphere of discovery, hard work and with a great coverage of many different scientific areas. In my final year I decided to go, under the ERASMUS program, to study ageing with Professor Suresh I. Rattan, in Aarhus, Denmark, a world leading scientist in the (almost forgotten) ageing field. Another good decision. Suresh was a great advisor in that he would have more questions than answers to offer. It was my first real lab, with very few people around, and I had a great feeling of freedom, responsibility and pure joy of "doing" science. During this time I managed to secure two Merit Scholarships from Calouste Gulbenkian Foundation and finish my degree with a good grade, which opened the door for a 4 year PhD scholarship from FCT. I just needed to find a lab to do it!
In my final Biochemistry year I happened to be introduced to Simon Davis, my current supervisor. The question his lab was working on seemed exactly what a biochemistry student should be ready to answer and so I decided to join the T-cell biology Group, at HIU, WIMM. I am now in the final year of my DPhil and once again I feel this was another good decision. Simon's enthusiasm on science and his quest for good, relevant, questions already had a profound influence in my scientific thinking. For the past 4 years I have been trying to understand how signal is transmitted across the T-cell membrane upon interaction between the T-cell receptor and its ligand, the major histocompatibility complex (MHC)-peptide. This is a fundamental question in biology: how does receptor triggering works? and in this particular case it is also a central problem in cell immunology as this interaction defines the immune response to both ourselves and to foreign organisms present in our body. Like many good problems this is a simple question but requires cutting-edge research, which is what the Davis Lab, the HIU and the WIMM in general, offer. In the course of my DPhil I have focused on different aspects and properties of the TCR and its triggering mechanism: receptor valency; the role of conformational changes during triggering; and how the balance between kinases and phosphatases present at the cell membrane affect TCR complex phosphorylation.
These 4 years studying at the Davis Lab gave me the confidence to pursue a career in science and keep myself busy with interesting problems in biology, and this, I wish, will be the best decision of all.
More than 50 mutations on CD3ε were tested for their ability to transmit signaling across the membrane. Surprisingly, as long as the TCR is expressed at the cell surface (x axis) it is able to activate T-cells (y axis), upon antibody binding to CD3ε. This indicates that a large conformational change is not required for TCR triggering
- James JR, McColl J, Oliveira MI, Dunne PD, Huang E, Jansson A, Nilsson P, Sleep DL, Goncalves CM, Morgan SH, Felce JH, Mahen R, Fernandes RA, Carmo AM, Klenerman D, Davis SJ (2011) The T cell receptor triggering apparatus is composed of monovalent or monomeric proteins. J Biol Chem 286: 31993-32001
- Fernandes RA*, Yu C*, Carmo AM, Evans EJ, van der Merwe PA, Davis SJ (2010) What controls T cell receptor phosphorylation? Cell 142: 668-669
- Dunne PD*, Fernandes RA*, McColl J*, Yoon JW, James JR, Davis SJ, Klenerman D (2009) DySCo: quantitating associations of membrane proteins using two-color single-molecule tracking. Biophysical journal 97: L5-7
- Rattan SI, Fernandes RA, Demirovic D, Dymek B, Lima CF (2009) Heat stress and hormetin-induced hormesis in human cells: effects on aging, wound healing, angiogenesis, and differentiation. Dose Response 7: 90-103
- Rattan SI, Sejersen H, Fernandes RA, Luo W (2007) Stress-mediated hormetic modulation of aging, wound healing, and angiogenesis in human cells. Annals of the New York Academy of Sciences 1119: 112-121
* these authors contributed equally to this work