Address

12, rue du Vieux-billard
1205 Genève
Switzerland

Phone nr

+41 (22) 379 34 86

Mobile

+41 (79) 535 06 29

E-mail

Contact me

Birth date

December 21, 1981

Nationality

Swiss

Marital status

Single

Available

From the 1^st of July 2010

Subject

TOR and SCH9 signaling pathways regulating ribosome biogenesis

Institute

University of Geneva, Department of Molecular Biology, Geneva, CH

Website

http://www.molbio.unige.ch/loewith/

Summary

The Target of Rapamycin Complex 1 (TORC1) is an essential multiprotein complex conserved from yeast to man. Its kinase activity is specifically inhibited by the macrolide antibiotic rapamycin. TORC1 deregulation in man is implicated in various diseases such as cancer, tuberous sclerosis complex and other hamartomatous syndromes.

As the signaling pathways that couple TORC1 to its distal readouts are not well understood, we employed a quantitative, label-free mass spectrometry approach to analyze the rapamycin-sensitive phosphoproteome in yeast. This study identified many novel TORC1 effectors and revealed how this complex plays a central role in eukaryote growth control.

Main tasks

∙ ³H-uracil ribosomal RNA metabolic labeling assays

∙ Gene expression assays by quantitative RT-PCR and primer extension assays

∙ Protein-protein interaction assays by co-immunoprecipitation or affinity purification

∙ Quantitative chromatin immunoprecipitation (ChIP) assays of various proteins

∙ Protein overexpression and purification from yeast and bacteria

∙ In vitro kinase assays with purified recombinant protein substrates and peptides

∙ Polysome profiles on sucrose gradients and ribosome purification from yeast cells

Collaborations

∙ Prof. Ruedi Aebersold (ETH Zürich, CH) for label-free quantitative phosphoproteomic screens

∙ Prof. Ann L. Beyer (University of Virginia, VA, USA) for Miller chromatin spreads and electron microscopy analyses.

∙ Prof. James R. Broach (Princeton University, NJ, USA) for transcriptome profiling by DNA microarrays

Teaching

Molecular genetics practical courses (Undergraduate lab course, 10 h / year)

Thesis defense

Planned on June 30^th 2010

Subject

HDAC8 as a potential isoform-specific Actin partner.

Institute

University Medical Center, Department of pathology and immunology, Geneva, CH

Website

http://pathology.unige.ch/patim/group-chaponnier.html

Summary

Actin is expressed in mammals as six isoforms showing different tissue expression patterns. Polymerized α-sm-Actin expression is directly correlated to cellular contractility and its ectopic expression is associated to various human pathologies such as hypertrophic scars.

Main tasks

∙ Study of HDAC8 tissue expression in rats and mice and correlation with Actin isoforms localization

∙ Study of HDAC8 localization by immunofluorescence microscopy upon the specific depolymerization of the α-sm-Actin cytoskeleton

∙ In vitro HDAC8-α-sm-Actin interaction assays upon Actin polymerization

Subject

The Wnt signaling pathway in breast cancer cells

Institute

Friedrich Miescher Institute, Basel, CH

Website

http://fmi.ch/html/research/research_groups/growth_control/nancy_hynes/nancy_hynes.html

Summary

Wnt proteins are small secreted lipid-modified growth factors implicated in various processes throughout mammalian development and adulthood such as cellular differentiation, tissue patterning. Dysregulation of Wnt signaling was shown to be implicated in a wide range of cancers including breast cancer.

Main tasks

∙ FPLC purification of the Wnt inhibitor sFRP1 from medium of 293T cells overexpressing the protein

∙ Development of luciferase reporter assays of Wnt-induced β-catenin activity in breast cancer cell lines (T47D, HC-11) to control sFRP1 activity

∙ Growth assays in breast cancer cell lines (T47D, HC-11, MCF-7, SkBr3) upon treatment with purified sFRP1

Subject

Construction of human viral vectors for the cystic fibrosis gene (CFTR)

Institute

University Medical Center, Department of Microbiology, Geneva, CH

Summary

The Sendaï paramyxovirus infects epithelial cells of the respiratory tract in humans and rodents but is not pathogenic in human adults. The virus ability to induce high levels of expression of genes recombined in its genome in infected cells suggested that it might be a vector of choice for gene therapy against airway epithelium diseases such as cystic fibrosis.

Main tasks

∙ Insertion of the CFTR gene in the Sendaï virus genome

∙ Reconstitution of active viral particles in BSR-T7/5 cells

∙ Amplification of the virus in fertilized chicken eggs

Subject

Leptin-mediated regulation of fatty acids metabolism and insulin resistance in mice

Institute

University Medical Center, Department of Medical Biochemistry, Geneva, CH

Summary

Leptin is a small peptide hormone mainly produced by white adipose tissues in mammals. Its production is increased by adiposity and antagonized by fasting. Leptin targets specific neurons in the central nervous systems to control both appetite and energy expenditure. Leptin may also signal directly to peripheral organs such as the liver and muscles to modulate fatty acids metabolism in part by regulating the activity of the Acetyl-CoA carboxylase enzyme.

Main tasks

∙ Glucose uptake assays in in vitro L6 myoblast culture models upon insulin stimulation

∙ Acetyl-CoA carboxylase enzymatic assays in mitochondrial subfractions of skeletal muscles in mice

∙ Analysis of Stearoyl-CoA desaturase 1 (target of Leptin) expression in Leptin-treated mice

Tasks

∙ Student coaching for applied inorganic/organic chemistry courses

∙ Replacement teacher for theoretical chemistry courses