The Project
Functional and proteomics-based analysis of human kinetochores.
Winner
Patrick Meraldi
ETH Zurich
Institute of Biochemistry
Zurich, Switzerland
www.bc.biol.ethz.ch
Swiss citizen Patrick Meraldi, 33 years old, graduated with a Masters in Molecular Biology from the University of Geneva in 1996, and in 1999 with a Ph.D in Molecular Biology from the same University. Since 2002, he has been a postdoctoral fellow in the Department of Biology at the Massechussetts Institute of Technology, in Cambridge, USA.
Award
€1,039,610
Project Description
Kinetochores(*) play a fundamental role in the regulation of chromosome segregation. They mediate chromosome attachment to the microtubules of the mitotic spindle. They also monitor chromosome-microtubule attachment and activate the spindle checkpoint in the presence of attachment defects.
Kinetochores and the spindle checkpoint machinery are still poorly understood in molecular terms, particularly in human cells. Recent studies have identified more kinetochore components. The next step for better understanding requires detailed functional analysis of kinetochore proteins. At the same time, to understand the overall organisation of kinetochores we need to identify additional components and define the protein interaction networks within kinetochores.
The aim of this project is to understand in molecular terms the organisation and regulation of kinetochores in human cells. It will reply on a combination of cell biological assays including live cell-imaging and gene inactivation using RNA interference to functionally characterise kinetochore proteins and a proteomics-based approach relying on biochemical purifications and mass-spectrometry, which aim to identify novel kinetochore components and define protein phosphorylation events at kinetochores.
(*) Definition of Kinetochore:
The kinetochore is the protein structure in eukaryotes which assembles on the centromere and links the chromosome to microtubule polymers from the mitotic spindle during mitosis.The kinetochore contains two regions: an inner kinetochore, which is tightly associated with the centromere DNA; and an outer kinetochore, which interacts with microtubules. (Source: Wikipedia)
