Divorcing chromosomes still need rings: investigate the roles of a ring-shaped protein in bacterial chromosome organisation and segregation (LEJ16RS)

This project is recruiting for a 1st January 2017 or 1st April 2017 start.

DNA, the genetic blueprint of living organisms, uses a 4-letter code to define the instructions for organisms to grow and replicate. As the encoded information is very large, the DNA string is extremely long. DNA must be folded nearly three orders of magnitude to fit inside a restricted space of the cell. It is even more challenging during chromosome replication and segregation. The cell now ends up with not just one but two extremely long pieces of strings. These strings must be folded somehow to avoid getting in the way of each other, otherwise it hinders the segregation of genetic materials to daughter cells. Our lab aims to understand how the bacterial chromosome is folded and segregated in vivo by focusing on a ring-shaped protein called Structural Maintenance of Chromosome (SMC) in an aquatic bacterium Caulobacter crescentus. This PhD project aims to understand (i) how SMC is loaded and distributed on the chromosome, (ii) how SMC mechanistically bring distal DNA close together spatially to organise the chromosome, and ultimately (iii) how these mechanisms assist daughter chromosome segregation.

The Caulobacter SMC protein is similar to human proteins called condensin and cohesin. Defective cohesin or condensin contributes to tumor formation. In addition, defective cohesin was thought to cause the genetic disease Cornelia deLange syndrome. The affected children have defects such as missing fingers, mental retardation, growth failure, heart defects, and other impairments. By employing a simpler living organism, this research into the role of SMC in Caulobacter will reveal an ancient, core function of the SMC family of proteins and thereby provide insights into the functions of human cohesin and condensin and how their malfunctions result in diseases such as cancers.

For further information and to apply, please visit the ’How to Apply’ page on our website:
http://students.jic.ac.uk/current-opportunities/how-to-apply/

References:

(1) Badrinarayanan, A., Tung Le, and Laub, M.T. (2015) Bacterial chromosome organization and segregation. Annu Rev Cell Dev Biol. 31:171-99
(2) Tung Le, Imakaev, M.V., Mirny, M.V., Laub, M.T. (2013) High-resolution mapping of the spatial organization of a bacterial chromosome. Science 342: 731-734
(3) Wang, X., Tung Le, Lajoie, B.R., Dekker, J., Laub, M.T. and Rudner, D.Z. (2015) Condensin promotes the juxtaposition of DNA flanking its loading site in Bacillus subtillus. Genes and Development 29(15):1661–75