"Lifeon the Edge: The Origins andProliferation of Protein Misfolding Diseases"
Presented by Chris Dobson
Cambridge
Natural proteins are a highly select group of molecules, andtheir properties have a number of very special characteristics when compared torandom sequences of amino acids, one of which is the ability to fold to uniqueand often highly intricate structures, a characteristic that has enabledbiological systems to generate a vast range of functions and an astonishingdegree of specificity in their chemical processes [C.M. Dobson, Nature 426,884-890 (2003)]. Because proteins areinvolved in every chemical process taking place within living systems, however,the failure of proteins to fold, or to remain correctly folded, can give riseto serious cellular malfunctions that frequently lead to disease. Oneparticularly important group of such diseases is associated with theaggregation of misfolded proteins into remarkable thread-like structures knownas amyloid fibrils, and includes disorders ranging from Alzheimer’s disease tolate-onset diabetes, conditions that are becoming increasingly common in ouraging populations. The manner in which the normal soluble forms of peptides andproteins can convert into these pathogenic amyloid structures is beinguncovered by a wide variety of in vitro experimental studies along withtheoretical simulations and bioinformatics studies [C.M. Dobson and F. Chiti,Annu. Rev. Biochem. 75, 333-366 (2006)]. As with folding, these studies areincreasingly being linked to events occurring in vivo using a variety ofstrategies. Of particular interest are experiments designed to link the genericprinciples of misfolding and aggregation to the effects of such processes inmodel organisms such as Drosophila (the fruit fly) [Luheshi et al., PLoS. 5,e290 (2007)]. This talk will try to draw together some of the ideas that areemerging from recent work in our laboratory including evidence for theextremely narrow boundary between normal and aberrant behaviour [Tartaglia etal., Trends Biochem. Soc. 32, 204-206 (2007)], and for the molecular mechanismof amyloid formation and proliferation [Knowles et al., Science 326, 1533-1537(2009)]. Such studies are leading to anincreasing level of understanding of the molecular origins and potential meansof prevention of many of the diseases associated with misfolding includingthose that give rise to neurodegeneration.
Hosted by Prof. Ann McDermott
Tuesday, March 30, 2010
Meet the speaker at 1:30pm in room 328 Havemeyer
Tea & cookies at 4:00pm in room 328 Havemeyer
Seminar at 4:30pm in room 209 Havemeyer
