Biomarkers in cancer development from time-resolved in vitro and clinical data.
The groups of Drs. S. Krivov and E. Paci work in the area of theoretical and computational biophysics with strong links with a number of world class experimental groups. Main topic of research is the analysis of the dynamics of complex (biological) systems by an original approach. The dynamics of the system as a whole (a systems biology perspective) is described in a simple but accurate way by constructing the underlying free energy landscape. The approach describes extremely well the complex dynamics of protein folding [1-3]. The ongoing research focuses on continuing methodological development of the free energy landscape framework and its application to the analysis of a wide range of important complex phenomena, e.g., disease dynamics, financial and social dynamics, data mining, artificial intelligence.
The current project involves application of the approach to construct optimal biomarkers which describe development of cancer using in vitro and clinical time-resolved data. Construction of a "good" biomarker is an important unsolved problem [4,5]. Considering the development of the disease as a manifestation of a complex dynamical process, a single index (the biomarker) that gives accurate description of the dynamics will be constructed out of panel of monitored parameters e.g., metabolomics, proteomics and genomics data. The biomarker can be used for fine-grained non-invasive monitoring of normal biological processes, pathogenic processes, or a pharmacologic response to a therapeutic intervention. The proposed approach treats explicitly the dynamical character of the process unlike established techniques such as principal component analysis. The project involves collaboration with Dr RL Hayward and Prof DA Cameron, University of Edinburgh and NHS Lothian. Successful completion will provide the student with high-profile publications and skills which will be in great demand in the future.
The Leeds Cancer Research UK Centre has up to four PhD studentships available to commence in October 2011. These are funded by either Cancer Research UK or Yorkshire Cancer Research.
Details of the formal application process can be found at the bottom of the page: http://www.findaphd.com/custadverts/leeds/ycr2011.asp
1. Krivov, S. V. & Karplus, M. Diffusive reaction dynamics on invariant free energy profiles.
Proc. Natl. Acad. Sci. USA. 105, 13841 (2008).
2. Yew ZT, Krivov S, Paci E, Free-energy landscapes of proteins in the presence and absence of force. J. Phys. Chem. B 2008, 112:16902-16907; Allen LR, Krivov S, Paci E Analysis of the free-energy surface of proteins from reversible folding simulations PLoS Comp. Biol. 2009, 5:e1000428
3. Krivov, S. V. Is protein folding sub-diffusive? PLoS Comput Biol 6, e1000921 (2010).
4. Sawyers, C. L. The cancer biomarker problem. Nature 452, 548 (2008).
5. Poste, G. Bring on the biomarkers. Nature 469, 156 (2011).
How good is research at University of Leeds in Biological Sciences?
FTE Category A staff submitted: 60.90
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