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Department of Physics
University of York
Tel: +44 (0)1904 324316
Fax: +44 (0)1904 322214
I have a multi-disciplinary trajectory in molecular modelling within the field of biological physics. My research interests are centred in developing novel computational tools to understand and predict how global mechanical properties of complex macromolecules such as DNA and RNA are built on the basis of their atomic fluctuations, with a particular emphasis in DNA flexibility and supercoiling.
Moreover, my research is focus on understanding and predicting the 3D architecture of genomes and its recognition properties on a broad range of length scales with a multi-scale approach: from atomistic and coarse-grained simulations to statistical-mechanics algorithms.
While genome sequencing has led to significant increases in the amount of genetic information available, we are still far from a comprehensive understanding of how genomes work. Recent experiments have shown that DNA looping and folding are essential mechanisms in the switching of genes between their on and off states . This has led to the idea that genetic information is also encoded through DNA topology and highlights the importance of studying the physical properties of DNA [2-4]. This project aims to predict DNA topology for improving genetic devices and genomes for utilisation in synthetic biology and gene therapy. Theoretical predictions will be compared with experiments done at the group of Mark Leake. Your project will allow you to:
1) Describe DNA loops with a physics-based computational methdology. Small loops are good models for understanding the essentials of gene regulation and also they are excellent gene-therapy vectors for introducing external genetic material in our cells. You will learn the most advanced techniques on molecular modelling
2) Develop a software for structural prediction at the genomic scale. The details learnt from small loops will be used for predicting the 3D architecture of genomes and improved them in the field of synthetic biology or biology engineering, absolutely critical for the production of biofuels, drugs or food additives. You will be trained in data analysis and bioinformatics as well as be familiar on the fields of biotechnology and synthetic biology.
Calcium is an essential ion for the condensation of biomolecules and for the formation of materials in living organism like bones and teeth. It also estabilizes a DNA mesh present on bacterial biofilm with the function to make bacteria resilient against antibiotic. Despite this enormous impact, the initial steps of calcium-molecule interaction and their impact on the nucleation of biominerals are not well understood. On this project we will describe the first stages of the interaction between Ca2+ and the protein osteopontin (OPN), which has been identified as a key protein regulating the growth of bone mineral. Further, the role of Ca2+ in the organisation of DNA will be investigated.
Theoretical predictions will be compared with experiments done at the group of Roland Kroger at the York JEOL Nanocentre. Your project will allow you to:
1) Describe DNA/Osteopontin folding caused by Ca2+ with molecular modelling. This is relevant for tackling the challenge of antibiotic resistence and for the field of bone regeneration. You will learn the most advanced techniques on molecular modelling
2) Detailed description of Ca2+ interaction using QM-based methodologies. A refinement of the interaction will be obtained by DFT with the leading software CASTEP/ONETEP in collaboration with Matt Probert, who is one of the main developers of the code.