As a part of the EPSRC funded project “Programming DNA topology: from folding DNA minicircles to revealing the spatial organization of bacterial genomes”, a fixed-term (3 years) pre-doctoral-level post is available under the supervision of Dr. Agnes Noy and Prof. Mark Leake at the University of York to carry out computational biophysics research on DNA topology using a model system of DNA minicircles. The work will be carried out in collaboration with the group of Prof. Mark Leake through the appointment of an additional PhD student for performing complementary experimental investigations using single-molecule biophysics techniques. The successful candidate for this PGRA in Biophysics post is expected to enrol in a PhD programme under the supervision of Dr Agnes Noy and co-supervision of Prof. Mark Leake as an integral part of the role.
You will perform atomistic and coarse-grained molecular dynamics simulations of rationally-designed DNA minicircles containing different genetic sequences for deciphering the “rules” of DNA folding, being simulations tested by experiments. Then, you will contribute to transfer the acquired structural information towards developing a statistical mechanics algorithm for the fast prediction of the topology of DNA.
This proposal falls within the EPSRC’s Grand Challenge “Understanding the Physics of Life” in addressing an extremely relevant and challenging biological question that needs to be tackled by a physics-based methodology. Recently, for example, it has been shown that DNA looping and folding are essential mechanisms in the switching of genes between their on and off states and that different patterns of gene expression are strongly influenced by genomic spatial organisation. This has led to the idea that genetic information is also be encoded through DNA topology and highlights the importance of studying the physical properties of DNA. Although being fundamental research, this study will also impact on the healthcare and synthetic biology sectors because tiny DNA minicircles are being recognised as highly efficient agents for gene therapy and because, through designing genome architecture, we will be able to produce better microorganisms for industrial biosynthesis.
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