Yeast Stress

Research Interests

Adaptation and survival to environmental challenges (stresses) are fundamental processes in all organisms. Microorganisms, in general, are widely exposed to oxidative environments as those imposed by chemical/physical stress agents and, in particular, pathogens to oxidative burst during phagocytosis. In fact, exposure to many fungicides and anti-cancer drugs generates oxidative stress. Similarly, exposure to temperatures below the optimal value has effects on the intracellular oxidative environment. Adaptation and survival depends on the accuracy and specificity of intracellular signal/stimuli propagation and efficient counter-acting/compensatory response(s). Despite the adjustments of gene expression at different levels, remodeling of transcription by RNA polymerase II (pol II) is a crucial process under stress stimuli. Our group research concerns the understanding of the molecular mechanisms of oxidative stress-signalling pathway(s), that culminate in discrete transcriptional events, involving two non-classical players as signaling molecules in oxidative stress pathway - TFIIB and folding machinery components.

Our research group location is at IGC - Marco Polo (CO wing)

If you are interested in working in our group, please send by email your CV and motivation letter to Lisete Fernandes.

Group Members

Ana Amorim	External Masters Student
	Tel: 21 446 4610
Dora Pinto	External Masters Student
	Tel: 21 446 4610

Research Project

Pol II basal machinery components as targets/signaling molecules of oxidative stimuli

Typically, general transcription factors (GTFs), as TFIIB, are assumed to exist in non-limiting pools and, therefore, ubiquously required for transcription initiation by Pol II independently of the environmental stimuli and gene(s) function(s). This project raises the question on the relevance and role of the so called GTFs when cells are under specific challenges.

Collaborators

Centro de Pesquisas Gonçalo Moniz/FioCruz & Hospital São Rafael, Salvador, BA, Brasil - Milena B. P. Soares

Research Project

Signaling of oxidative stress through cytoskeleton

Despite the role of all six Gim subunits in actin/tubulin biogenesis in the yeast Saccharomyces cerevisiae, the mammalian homologue of Gim2 interacts with the tumor suppressor VHL; VHL has targets on oxygen-sensing pathways. By integrating the role of the six Gim subunits in stress signaling pathways leading to transcriptional events, we question if specific Gims per se impinge on transcription or if they simply sustain the alterations of cytoskeleton under oxidative environments and, in both cases, the existence of evolutionary conserved targets shared by different stress signaling pathways.

Collaborators

IGC/Oeiras Isabel Gordo

Research Project

Crosstalk of oxidative stress and cold signaling pathways

The Yap family of bZIP transcriptional factors in Saccharomyces cerevisiae contains members which are central players in cellular responses to stress, such as: Yap1 in oxidative and cold signals, and Yap4 in response to compounds affecting cytoskeleton as well as in cold. This project relies on both bZIP activities to identify common players in cold and oxidative responses. In addition, genetic tools from this project, such as yap4 loss-of-function mutants, allow to assess cytoskeleton contribution for signaling into transcription.

Collaborators

Centro de Pesquisas Gonçalo Moniz/FioCruz & Hospital São Rafael, Salvador, BA, Brasil - Milena B. P. Soares

Publications

Coelho et al. (2010). Differential contribution of Gim/Prefoldin subunits to specific stress gene expression. (submitted)

Perfeito L, Fernandes L, Mota C and Gordo I. (2007). Adaptive mutations in bacteria: high rate and small effects Science 317 :813-815

Faria, J.P., Fernandes, L. (2006). Protection against oxidative stress through SUA7/TFIIB regulation in Saccharomyces cerevisiae. Free Radic. Biol. Med. (in press)

Dionisio, F., Conceição, I.C., Marques A.C.R., Fernandes, L. and Gordo, I. (2005). The evolution of a conjugative plasmid and its ability to increase bacterial fitness Biol. Lett. 1 :250-252

Cyrne, L., Martins, L., Fernandes, L., Marinho, H.S. (2003). Regulation of antioxidant enzymes gene expression in the yeast Saccharomyces cerevisiae during stationary phase Free Radic. Biol. Med. 34 :385-393

Fernandes, L., Rodrigues-Pousada, C., Struhl, K. (1997). Yap, a novel family of eight bZIP proteins in Saccharomyces cerevisiae with distinct biological functions Mol. Cell. Biol. 17 :6982-6993

Bossier, P., Fernandes, L., Vilela, C., Rodrigues-Pousada, C. (1994). The yeast YKL714 gene situated on the left arm of chromosome XI codes for an homolog of the human ALD protein Yeast 10 :681-686

Dujon, B. (Ö), Fernandes, L. (Ö), Becker, I. (1994). The complete DNA sequence of chromosome XI of Saccharomyces cerevisiae Nature 369 :371-378

Bossier, P., Fernandes, L., Rocha, D., Rodrigues-Pousada, C. (1993). Overexpression of YAP2, coding for a new yAP protein, and YAP1 in Saccharomyces cerevisiae alleviates growth inhibition caused by 1,10-phenantroline J. Biol. Chem 268 :23640-23645

Bossier, P., Fernandes, L., Rodrigues-Pousada, C. (1992). Yeast genes overcoming growth arrest induced by 1,10-phenantroline Cell Biology 69 :7-11