My research interests span a broad spectrum of scientific disciplines from the early evolutionary events of life on earth to developing novel mathematical and computational methods for elucidating complex systems of gene regulation. Though they seem unconnected, the unifying feature of my work is the interplay between mathematical tools and wet-bench science, and how each can be used to inform and direct the other.
The structure/function relationship of the genome
Genomes are not just libraries of information they are dynamic storage-machines which temporally control access to information through a variety of different mechanisms. It is clear that long-range physical interactions between discrete chromosomal regions play an important role in how that information is accessed and expressed across the “tree-of-life”. Evidence for this comes from a variety of sources and experiments; from the earliest observations on isolated bacterial “nucleoids” to recent experiments mapping the entire 3D structure of the Human genome using parallel sequencing. All of these lines of evidence indicate that genome function is controlled at multiple different levels and scales of organisation, from the linear sequence of the genome itself through nucleosome structure to large-scale chromosome arrangement in the nucleus. I am interested in understanding how 3D genome organisation influences how the genome works. I am particularly interested in the genomes of plants. Plant genomes can be very large, they are often characterised by massively paralogous gene families and they exploit all manner of regulatory mechanisms to control their function. So there is lots to study and understand and a whole manner of mechanisms that can be exploited to meet future food production demands.
Using comparative omic technologies to understand convergent biology
It is predicted that by 2050 we will need to increase food production by at least 50%. At the same time, improvements in farm yields of our major crops has slowed down. This is clearly a serious global problem that needs to be addressed. There are few examples of inventions in the natural world that could produce such large increases in our domestic crops, but one that has this potential is known as C4 Photosynthesis. You can think of C4 photosynthesis as the plant equivalent of “division of labour,” the idea that kick-started the industrial revolution. By dividing up the tasks of capturing CO2 from the atmosphere and storing it as sugars into two different cells within the leaf, C4 plants essentially invented the production line and dramatically increased their overall efficiency. This saving allows them to grow more quickly and store more carbon in their leaves, seeds and fruits. Perhaps unsurprisingly given the advantage that this optimisation can confer, C4 photosynthesis has evolved at least 62 different times in at least 18 different families of plants. What's more, it's so efficient that although C4 plants only make up 3% of plants on earth they are responsible for 20-30% of all CO2 capture by plants. The shear number of times that C4 photosynthesis has been re-invented in nature combined with the urgent need to improve crop yields has led to international efforts to engineer C4 photosynthesis into non-C4 crops such as rice (http://c4rice.irri.org).
In this work, which is a collaborative effort linking Universities in Cambridge, Torronto, Alberta and the International Rice Research Institute in the Philippines, we are trying to learn from evolution how it is that C4 plants (like corn, sugar cane and millet) evolved from their non-C4 ancestors. One way in which we are currently doing this is by using new sequencing technologies to read and quantify the genes of more than 40 different C4 plants and their closest non-C4 relatives. Our discoveries are revealing the extent to which different species have used the same genes to achieve C4 photosynthesis and how many different ways evolution has found of reaching the same solution. We hope to use this information to engineer these changes into rice and thereby use natural diversity to feed the planet into the future.