On Wednesday, October 8th, 2008 Nuno Rocha will defend his thesis titled "Molecular basis for the control of motor-based transport of MHC class II compartments" in order to obtain the doctorate degree from Leiden University. His promoter is professor Jacques Neefjes in whose lab this work was performed.
The studies presented in his thesis aimed at gaining a more advanced level of understanding of the molecular mechanisms governing intracellular transport of MHC class II compartments or MIICs. These specialized lysosomal-related organelles are of crucial importance in antigen presentation by major histocompatibility complex class II (MHC II) molecules to CD4 T cells for immune responses to pathogens and tumors.
Most of the research conducted in the field of MHC II antigen presentation has focused on the events taking place inside the specialized MIIC. Consistently, considerable effort has been geared toward the development of strategies to manipulate these events. Although this has undoubtedly yielded significant results, extending our focus to include other aspects of the cell biology of antigen presentation, such as intracellular transport and trafficking of MIICs, will almost certainly increase the spectrum of targets for therapeutic intervention in undesired autoimmunity and transplant rejection or manipulation of presentation of vaccine antigens, as well as the development of innovative modes to manipulate immunity against invasive pathogens and tumors.
In his thesis, a novel molecular mechanism is postulated and aims at explaining the complex pattern of intracellular motility exhibited by MIICs, an ill-defined process for many years. Notably, a signaling cascade initiated by the activation of a lysosomal specific molecular switch and the surprising contribution of cholesterol to the control of MIIC transport are now described and may contribute to the understanding of pathologies ascribed to malfunctioning of the endolysosomal system (which can include immunity- and pigmentation-related syndromes), as well as those associated to dysfunction in cholesterol homeostasis.
Proposition 9 which accompanies the thesis states: Being a graduate student is like becoming all of the Seven Dwarves. In the beginning you’re Dopey and Bashful. In the middle, you are usually sick (Sneezy), tired (Sleepy), and irritable (Grumpy). Finally, everyone calls you Doc, and then you’re Happy.
The thesis defense is open to the public and will take place in the Academiegebouw, Rapenburg 73 of Leiden University, at 13.45 hours.