Research directions
Regulation of gene expression by cell growth and differentiation factors
Our research focuses on the control of DNA transcription and replication by human nuclear proteins called CTF/NF-I
CTF/NF-I proteins recognize and bind specific sites on DNA, which activates the expression of adjacent genes and increases the replication of particular viruses. We aim at determining the regulatory mechanisms involved and at further understanding the regulation of such activities by peptidic hormones involved in cell growth and division. Our work has implied the chromatin structure in CTF/NF-I actions, whereby these proteins may alter and/or modulate the nucleoprotein architecture of nucleosomes
Our long term goals are to understand how the cell (and the viruses that infect them) specifically controls and coordinates gene activity and replication, and how these activities are regulated by growth factors implied in several human disorders such as tumor cell growth and fibrotic diseases
This project is supported by the Swiss National Science Foundation and by the State of Vaud
Over-expression of genes of biotechnological interest in mammalian cells in culture
This project aims at producing immunoglobulins with a therapeutic potential
Stable and efficient production of heterologous proteins in mammalian tissue culture cells is still limited by technological bottlenecks. For instance, the establishment of stable CHO lines demands the generation and screening of numerous transfected cells clones, in order to detect the most efficient producer cells. In this project, we are constructing genetic vectors for the efficient and rapid generation of stable transfected lines with high production capacities. We are currently expressing Rhesus directed monoclonal antibodies for the prophilaxis of the
hemolytic anemia of the newborn
This project is supported by the Swiss Priority Program Biotechnology (Module 1) and by the Swiss red cross central laboratory in Bern (ZLB). It is carried on in collaboration with partners at the Center of Biotechnology of the University of Lausanne (UNIL) and the Federal Institute of Technology at Lausanne (EPFL), at the Department of Chemistry at EPFL, and at the Swiss red cross central laboratory in Bern (ZLB)
Characterization of regulatory genomic regions with bio-informatics tools
This project aims at the development of computer systems for the faithful recognition of gene expression regulatory regions in eukaryotic genomic DNA sequences
Our contribution to the project is the development of methodological tools and the generation of experimental data for the efficient detection of DNA binding sites for regulatory proteins
This demands technologies for the time-efficient determination of the affinities of regulatory proteins with a panel of specific DNA sequences, and the correlation of such values with the regulatory potential of the sequences, as determined in tissue culture cells. These studies should contribute to the development of predictive tools for the realistic recognition of potential regulatory sequences on genomic DNA, in collaboration with the project's partners
This project is supported by The Swiss Office for Education and Science and by the Ludwig Institute for Cancer Research. The project is carried on in collaboration with Dr. P. Bucher (Institut de Recherche Expérimentale sur le Cancer) and Dr. V. Jongeneel (Institut Ludwig), both in Epalinges, Switzerland
Development of regulated expression vectors for somatic gene therapy
This project aims at the construction of genetic vectors for the efficient and regulated expression of transgenes in ex vivo gene therapy approaches
Safe and efficient somatic gene therapies demand tight regulation of transgene expression in the patient, using medically acceptable drugs. In this project, we are constructing expression vectors whereby the transgene is regulated by a genetic network of engineered activators and silencers of transcription. These vectors will be used for the stable expression of neurotrophic factors in cell lines used for the ex vivo gene therapies of neurodegenerative diseases
This project is supported by the Swiss National Research Program 37: Somatic Gene Therapy, by a carrier award of the Swiss confederation and by a Priority project of the University of Lausanne
The project is carried on in collaboration with partners at the CHUV (State of Vaud University Hospital)
