Molecular Microbiology & Biotechnology
Tel Aviv University
Martin Kupiec, Professor, Molecular Microbiology & Biotechnology, Tel Aviv University, Israel
DNA repair: Our cells are constantly exposed to radiation and chemicals that cause damage to the DNA or even break the chromosomes in pieces. Even natural cellular metabolism creates oxidative stress and DNA damage. Luckily we have efficient mechanisms to repair the damage. Stability of the eukaryotic genome: Normal cells have remarkably stable karyotypes. You can easily identify to what species a cell belongs, just by looking at its chromosomes. However, cancer cells lose this stability, and start accumulating translocations, deletions, amplifications, etc. Many of the endpoints of these rearrangements fall in repeated sequences (sometimes called “junk DNA”) that fill-up our genomes. What prevents a high level of chromosomal aberrations as a consequence of recombination between repeated sequences? Telomeres: Telomeres are nucleoprotein complexes at the end of the eukaryotic chromosomes. We would like to know how do all these genes work together to regulate telomere length. Are there several pathways? Complexes? What are the interactions between the various elements? To answer these questions we are using a combination of Molecular Biology, Systems Biology, Genetics and Biochemistry. Bioinformatic models are used as a basis to plan possible experiments. The results are then incorporated into the model, to generate more predictions in a continuous cycle that progressively refines the model. The TOR protein kinase: The TOR protein kinases exhibit a conserved role in regulating cellular growth and proliferation. We would like to answer some of the following questions: What is the function of each of the Tor proteins? What is the nature of their interactions? How are they regulated? Why are mammalian cells and budding yeast so affected by rapamycin (an anticancer drug in clinical trials), whereas fission yeast can grow in its presence? How do the Tor proteins integrate signals from the environment to know when to grow? And how do they talk to the cell cycle machinery to coordinate growth (in volume) with cell division?
Yosef N., Ungar L., Zalckvar E., Kimchi A., Kupiec M., Ruppin E., Sharan R. (2009) Toward accurate reconstruction of functional protein networks. Mol Syst Biol. 5:248.
Schonbrun, M., Laor D., Lopez-Maury-L., Bahler J., M. Kupiec and Weisman R. (2009) The TORC2 complex regulates DNA damage response, gene silencing, and telomere length maintenance. Mol. Cell. Biol., 29(16):4584-4594.
Tuller T, Kupiec M. and E. Ruppin (2009) Co-evolutionary networks of genes and cellular processes across fungal species. Genome Biol. 10:R48.