|
Group Members | Reseacrh Interests | Publications
| Opportunities |
Dr.
CÉSAR RONCERO MAILLO. (Profesor USAL) crm@usal.es
Dr. ANGEL DURÁN BRAVO. (Investigador CSIC) adb@usal.es
Dr. JAQUELINE PÉREZ PAZOS. (Becaria
Postdoctoral) jperezpazos@usal.es
ABIGAIL REYES VALERÓN. (Becaria Predoctoral) abigail@usal.es
ALBERTO GOMEZ SANZ. (Becario Predoctoral) agsanz@usal.es
CARLOS SACRISTÁN LÓPEZ. (Becario Predoctoral)
csacris@usal.es
ROSARIO VALLE VICENTE. (Tecnico de laboratorio contratado
USAL) rvv@usal.es
Cell
Wall and Morphogenesis in Yeast Group 03 - 08
RESEARCH
INTERESTS
Fungal cell wall is widely
recognized as an ideal antifungal target although only a single family
of compounds that inhibit its synthesis have reached therapeutic value.
The reasons for that are multiple and include the poor knowledge on how
this structure is formed combined with some technical limitations in the
identification of these compounds. Our work is intended to combine the
technological power of yeast Saccharomyces cerevisiae with the work on
pathogenic fungi in order to understand how fungal cell wall is formed
and to provide alternative ways in the identification of new antifungal
compounds. Most of the work will be concentrated in a single polymer,
chitin, essential for the cell wall construction.
Using S.cerevisiae we will attempt to understand how the major chitin
synthase (CSIII) is activated at the plasma membrane using a combination
of molecular and cellular biology techniques. We will attempt to establish
how the different postranslational modifications of Chs3p mediate its
insertion in the PM modulating its endocytic turnover, both key elements
in the regulation of chitin synthesis.
In addition, and using the pathogen Aspergillus fumigatus as model we
will investigate the role of different CSs in the construction of its
cell wall. Most fungi, including A.fumigatus, contain a high degree of
genetic redundancy in their CSs and the analysis of single ?chs mutants
did not offer conclusive answers. We will therefore construct and characterize
multiple mutants of those CS focusing in the family 2 enzymes, which is
expected to include the major in vivo activities in filamentous fungi.
This characterization will include intracellular localization of these
proteins. Considering that it will be impossible to characterize these
enzymatic activities in the original fungi we will characterize these
activities through the use of chimaeric proteins expressed in S.cerevisiae.
The major efforts will be dedicated to the study of the structure/function
relationship towards explaining the sensitivity of different enzymes to
CS inhibitors. This study will include enzymes form additional pathogens
as Candida albicans or Cryptococcus neoformans. Based in this approach
we expect to set up the methodology for HTS assays for selecting inhibitors
of this type of CS, a task nor previously reported.
An additional part of our effort will focus in the cell wall as a whole,
turning back to S.cerevisiae as genetic model. We will attempt to define
genetically the interaction of the RIM101 and PKC signal transduction
cascades in cell wall construction, whose simultaneous absence produces
cell death. The identification of genetic suppressors of this lethality
will allow the identification of new genes involved in fungal cell wall
construction. The characterization of those will add new clues in the
assembly of this structure and also we eventually identify new potential
target for antifungal compounds.
PUBLICATIONS
Reyes, A., Sanz, M., Duran, A., Roncero, C. (2007). Chitin
synthase III requires Chs4p-dependent translocation of Chs3p into the
plasma membrane. J Cell Sci.
120: 1998-2009.
Castrejon, F., Gomez, A., Sanz, M., Duran, A., Roncero, C.
(2006) The RIM101 pathway contributes to yeast cell wall assembly and
its function becomes essential in the absence of MAP kinase Slt2p .Eukaryot.
Cell. 5: 507-517
Garcia-Rodriguez, l.J., Valle, R., Duran,A., Roncero, C. (2005)
Transient activation of the cell integrity signal pathway in response
to hyperosmotic shock. FEBS Lett.
579: 6186-6190.
Roncero, C. (2002) The genetic complexity of chitin synthesis
in fungi. Current Genetics. 41:
367- 378.
Sanz, M., Trilla, J.A., Duran, A. Roncero, C. (2002)
Control of chitin synthesis through Shc1p, a functional homologue of Chs4p
specifically induced during sporulation.
Mol. Microbiol. 43:1183-1195.
Trilla, J.A., Duran, A., Roncero,
C. (1999) Chs7p, a new protein involved in the control of protein
export from the ER that is specifically engaged in the regulation of chitin
synthesis in Saccharomyces cerevisiae. J.
Cell Biol. 145: 1153- 1163.
OPPORTUNITIES
If you are interested in any of
our work and would like to join the group as a graduate student or postdoctoral
fellow, then please write to Dr.
CÉSAR RONCERO ( crm@usal.es)
and include a copy of your current C.V.
