We AIM to UNDERSTAND the molecular details of how Cells organise histone supply chains to support chromatin biology
Histone proteins are packed full of lysine and arginine residues, in other words they are very positive(ly charged). This is what makes them so good at packaging DNA - histones effectively neutralise the negative charge on the phosphate backbone of DNA. However, histones are more than just a packaging system, they are an important layer of regulation that controls access to the genetic code within DNA base pairs. Histones are so important to cells that many people across the world research how histones influence cell biology. This field of research is called chromatin biology. In my lab we believe that histone supply chains are fundamentally important to the functionality of chromatin. It's not just my lab though, the cell also thinks so, as there is a whole host of cellular machinery dedicated to supplying histones to chromatin. Key components of this machinery are histone chaperones and they stop histones sticking randomly to DNA in the cell and make sure that they are used to create nucleosomes instead - nucleosomes are the building block of chromatin.
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Histone chaperones are a set of proteins that act to prevent histones from non-specifically associating with DNA, however they provide so much more than this functionality alone. Histone chaperones integrate with many cellular processes - nuclear import, histone post-translational modification catalysis, nucleosome assembly and chromatin remodelling, to name but a few. My work has described how histone chaperones operate in a network-like structure, called, you guessed it, "the histone chaperone network". A key component of this network is the histone co-chaperone complex in which two or more histone chaperones form an interaction mediated by histones. By probing the biology of the histone chaperone network we have identified new links to other processes like protein folding and insights into mechanisms of silencing gene expression.
We hope that by studying histone supply chains mechanistically, and in the context of cancer, we will be better placed to translate our discoveries into real-world health benefits for cancer patients. This is why I chose to become a scientist, and why many of us do.