Genomics and Stress Laboratory
The genomics and stress laboratory works in the mechanisms involved in homeostasis control when yeast cells are exposed to different environmental cues. The function of Yap transcription factors in stress response is investigated.
Phone (+351) 214469624
Metals are some of the most important environmental toxics that cause acute and chronic adverse health effects including cancer. The ubiquity of arsenic in the environment allowed the evolution of very similar defence mechanisms in organisms ranging from bacteria to man. The genome-wide set of S. cerevisiae deletion strains provided the understanding of mechanisms by which arsenic trioxide selectively kills acute promyelocytic leukemia cells. S. cerevisiae is an attractive biological model with powerful genetic and genomic approaches. The increased levels of arsenic in the environment is mediated by the expression of the ACR (Arsenic Compound Resistance) cluster that is composed of genes YAP8 (ACR1), ACR2 and ACR3. Yap8 is the key regulator of the expression of the arsenate-reductase Acr2 and the plasma membrane arsenite efflux transporter Acr3. Yap1 contributes to arsenic stress response by regulating the expression of a vacuolar arsenite detoxification pathway encoded by Ycf1. Yap1 also plays an important role in arsenic adaptation by controlling the redox homeostasis disturbed by inorganic arsenic compounds. To analyze whether Yap1 and Yap8 use similar mechanisms to transduce the stress signals to the basal transcription machinery, we are addressing the effect of mutations in specific subunits of the tail module of the mediator complex.
Furthermore, iron is an essential nutrient needed for almost every organism on earth, because it is utilized as cofactor in key redox reactions of many central biochemical processes. The abnormal Fe accumulation, in either excessive or insufficient levels, underlies several human diseases including hereditary hemochromatosis, and Fe-deficiency anaemia. To give the cells iron homeostasis control, they possess not only the ability to regulate iron acquisition but also to store iron once it is absorbed. The mechanisms of gene expression by which cells control iron overloading are being investigated.
Nitric oxide (NO) is a membrane-permeable free radical biologically produced by the NO synthase family of enzymes. Its exposure induces in cells a response at the transcriptional level, in which transcription factors are key elements. RNS can mediate similar chemical events to those involved in ROS detoxification. NO detoxification in prokaryotic and eukaryotic microorganims is studied in order to get insights into the evolutionary conservation of the mechanisms involved. The identification of a common transcription factor to both stresses is investigated.
- Regina Menezes, Post-Doc
- Catarina Pimentel, Post-Doc
- Tracy Nevitt, Post-Doc
- Jorge Pereira, PhD Student
- Catarina Amaral, PhD Student
- Liliana Nascimento, PhD Student
- Fabio Silva, PhD Student
- Iulia Bleoanca, PhD Student, FEBS Fellow
- Ana Raposo, Master Student
- Joana Ropio, Master Student
- Ruta Grinyte, undergraduated student
- Pereira J., Pimentel, C., Amaral, C., Menezes, R.A. and Rodrigues-Pousada, C. (2009) Yap4 PKA- and GSK3-dependent phosphorylation affects its stability but not its nuclear localization, Yeast. 2009 Dec;26(12):641-53.
- Menezes RA, Amaral C, Batista-Nascimento L, Santos C, Ferreira RB, Devaux F, Eleutherio EC, Rodrigues-Pousada C. (2008) Contribution of Yap1 towards Saccharomyces cerevisiae adaptation to arsenic-mediated oxidative stress. Biochem J. 2008 Sep1; 414(2):301-311.
- Dulce Azevedo, Liliana Nascimento, Jean Labarre, Michel B Toledano, Claudina Rodrigues-Pousada (2007) The S. cerevisiae Yap1 and Yap2 transcription factors share a common cadmium-sensing domain FEBS Lett. 23;581(2):187-95.
For further information please visit the laboratory's website
Para fazer frente às modificações do meio ambiente as células/organismos reprogramam a expressão genética através da indução de novas proteínas essenciais para a sobrevivência assistindo-se também à repressão das proteínas que não são de imediato necessárias. Este conjunto de eventos faz com que a homeostase seja restabelecida permitindo que o organismo/células funcionem eficientemente numa larga variedade de condições ambientais. O nosso laboratório estuda todos estes mecanismos particularmente queremos compreender como é que os genes induzidos durante a adaptação a estas condições são regulados a nível transcricional. Abordámos estes processos na levedura Saccharomyces cerevisiae, também designada por fermento de padeiro, um modelo excepcional graças à manipulação fácil da sua genética e genómica apresentando semelhanças genéticas aos eucariontes superiores. O modelo anaeróbio Desulfovibrio gigas, cujo genoma está praticamente anotado, é também estudado.