Earnshaw Lab Research Overview

Chromosomes contain the cellular DNA plus proteins that package it and regulate its expression. For most of the life of the cell, the chromosomes are contained within the cell nucleus, and cannot easily be distinguished from one another. Chromosome structure changes dramatically during cell division (mitosis) and cellular suicide (apoptosis). We use a combined approach featuring genetic analysis in Drosophila melanogaster and chicken DT40 cells, four-dimensional wide-field microscope imaging and biochemical analysis in extracts from cultured cells and Xenopus eggs to study the roles of chromosomal proteins during mitosis and apoptosis. In the 1980s, we were the first lab to show that certain chromosomal proteins, which we termed chromosomal passengers, integrate what the chromosomes and cellular skeleton are doing during mitosis. The proteins we study, inner centromere protein (INCENP), Aurora-B kinase and survivin, help organize the chromosomal movements during the first part of mitosis and then leave the chromosomes and are involved in cleavage of the cell. One major effort in the group is aimed at determining the molecular basis for these very different activities. We are also working to identify new proteins of the centromere, the chromosomal re-gion that directs the interactions between chromo-somes and the molecular machinery that partitions them to daughter cells during mitosis. Our studies of apoptosis, originally centered around a cell-free extract that reproduces the nuclear events of apoptosis together with their physiological regulation. We have used these extracts to study how proteases called caspases disassemble the nucleus during apoptosis. We are also dissecting at the various pathways for condensation of the chromatin during apoptosis, focusing in particular on the caspase activated DNase CAD.