Cell Damage and Repair
The course schedule can be found here
Background and Goals:
Accumulation of misfolded/ damaged and
aggregation-prone proteins is a common feature of ageing and underlies the
development of several ageing-related diseases. A deregulation of protein
homeostasis - proteostasis - has been widely accepted as a major aspect of ageing and a leading cause of the
development of late onset neurodegenerative disease. To maintain proteostasis,
cells evolved a network of molecular chaperones that assist protein folding,
maturation and trafficking. Polypeptides that failed to attain the right 3D
structures are degraded by specialized mechanism thus preventing aggregation
and potential proteotoxicy. A failure to maintain, repair and turnover
biomolecules has been often associated with ageing and neurodegenerative
diseases in yeast, worms, flies and mice. This course is designed for
clinicians and basic scientists with interests in aging and relations between
aging, neurodegeneration, and age-related diseases. The course will cover
topics from basic research, that includes the molecular mechanisms associated
with protein damage and the proteolytic machinery that functions to remove such
damaged and cytotoxic material, to translational research, using animal models
as tools to study how these mechanisms may contribute to ageing and development
of age-related diseases.
Paulo Pereira, FMUC Ehud Cohen, School of Medicine, The Hebrew University of Jerusalem, Israel
Henrique Girão, FMUC
Joana Simões Correia, FMUC
Lectures will be by global leaders in their field. The course will take place in the afternoon, being the first 3 hours with lectures and the second half of the afternoon will be spent attending journal clubs or evaluating grant proposals that the students will prepare and present to their colleagues and the faculty. The students will also do a short presentation, along with others, of how the course aids their career, including relationship building. (For detailed description of the program please see doc in attachment.
The Course will cover the following topics:
1. Protein folding and quality control (chaperones)
2. Degradation mechanisms (proteasomes and autophagy)
3. Cellular responses to the accumulation of misfolded protein (the heat shock response, UPRER and UPRmt)
4. The regulation of stress response mechanisms at the organismal level
5. Conformational diseases and neurodegenerative disorders
6. Deposition of non-degradable proteins in specialized sites (aggresomes, JUNQ and IPODs)
7. Aging as a key aspect of protein misfolding and disease
8. The manipulation of aging as a strategy to prevent the onset of neurodegenerative maladies
1. Temporal requirements of heat shock factor-1 for longevity assurance. Volovik Y, Maman M, Dubnikov T, Bejerano-Sagie M, Joyce D, Kapernick EA, Cohen E, Dillin A. Aging Cell. 2012 Jun;11(3):491-9.
2. Quality control compartments coming of age. Ben-Gedalya T, Cohen E. Traffic. 2012 May;13(5):635-42.
3. Reduced IGF-1 signaling delays age-associated proteotoxicity in mice. Cohen E, Paulsson JF, Blinder P, Burstyn-Cohen T, Du D, Estepa G, Adame A, Pham HM, Holzenberger M, Kelly JW, Masliah E, Dillin A. Cell. 2009 Dec 11;139(6):1157-69.
4. Ageing and protein aggregation-mediated disorders: from invertebrates to mammals. Dillin A, Cohen E. Philos Trans R Soc Lond B Biol Sci. 2011 Jan 12;366(1561):94-8.
5. The insulin paradox: aging, proteotoxicity and neurodegeneration. Cohen E, Dillin A. Nat Rev Neurosci. 2008 Oct;9(10):759-67.
6. Autophagy modulates dynamics of connexins at the plasma membrane in a ubiquitin-dependent manner. Bejarano E, Girao H, Yuste A, Patel B, Marques C, Spray DC, Pereira P, Cuervo AM. Mol Biol Cell. 2012 Jun;23(11):2156-69.
7. Endoplasmic reticulum quality control: a new mechanism of E-cadherin regulation and its implication in cancer. Simões-Correia J, Figueiredo J, Oliveira C, van Hengel J, Seruca R, van Roy F, Suriano G. Hum Mol Genet. 2008 Nov 15;17(22):3566-76.