How does Structural Maintenance of Chromosomes (SMC) protein interact with DNA to organise bacterial chromosomes?

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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. To fit this string into the restricted space of the cell, the DNA must be folded in a specific way in 3-dimensional space. This folding has extremely important implications for the functioning of all living organisms and yet it is very poorly understood how this structure is established and maintained, especially in bacteria. This research proposal aims to understand how a protein called Structural Maintenance of Chromosomes (SMC) folds the chromosome in an aquatic bacterium called Caulobacter crescentus. Specifically, we aim to:(i) understand the behaviour of individual SMC molecule in the cell when they are on or off DNA(ii) understand how RNA polymerases move SMC around on the chromosome(iii) discover new interacting partners that together with SMC organise the bacterial chromosomeThe Caulobacter SMC protein is similar to human proteins called condensin and cohesin. Defective cohesin or condensin contributes to tumour formation. Indeed, in colorectal cancer, a significant fraction of cancerous tissues was found to have defects in cohesin or associated genes. 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. I anticipate that, by employing a simpler living organism, my 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 disease.