Research Interests
Yeast Metabolism
We are developing a number a techniques for understanding the metabolism of bakers' yeast (Saccharomyces cerevisiae). At the heart of this is a classical inverse problem, which requires the iterative interplay between mathematical models of our system and experimental measurements with which the model may be compared. In partcular, we have developed a method for producing a “first guess” kinetic model of metabolism, based on linlog kinetics. Becuase of the minimal requirement for experimental data, it may easily be applied to existing genome-scale stoichiometric models.
Tumour Respiration
Tumour cells invariably evolve to rely on anaerobic respiration for energy production, despite it being highly inefficient. This results in increased lactic acid production, inducing acidification of the tumour tissue and surrounding normal tissue. An excellent review article on the topic may be found here.
Using mathematical techniques, we have approached the problem of understanding the causes and consequences of tumour acidity from three directions:
- Analysis of tumour pH images, with a view to their use as a diagnostic tool.
- Using cellular automata to understand the evolutionary pressures leading to metabolic changes during carcinogenesis.
- Using differential equations to model how these metabolic changes give tumour cells a proliferative advantage during growth.
Bio
Publications
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K Smallbone, RA Gatenby, PK Maini.
Mathematical modelling of tumour acidity.
J. Theor. Biol. In press. (doi)
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MJ Herrgård, N Swainston, P Dobson, WB Dunn, KY Arga, M Arvas, N Blüthgen, S Borger, R Costenoble, M Heinemann, M Hucka, N Le Novère, P Li, W Liebermeister, ML Mo, AP Oliveira, D Petranovic, S Pettifer, E Simeonidis, K Smallbone, I Spasić, D Weichart, R Brent, DS Broomhead, HV Westerhoff, B Kırdar, M Penttilä, E Klipp, BØ Palsson, U Sauer, SG Oliver, P Mendes, J Nielsen, DB Kell.
A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology.
Nature Biotech. In press.
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CJ Kelly, K Smallbone, JM Brady.
Tumour glycolysis: The many faces of HIF.
J. Theor. Biol. In press. (doi)
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K Smallbone, E Simeonidis, DS Broomhead, DB Kell (2007)
Something from nothing: Bridging the gap between constraint-based and kinetic modelling.
FEBS J. 274: 5576-5585 (doi)
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K Smallbone, DJ Gavaghan, PK Maini, JM Brady (2007)
Quiescence as a mechanism for cyclical hypoxia and acidosis.
J. Math. Biol. 55: 767-779 (doi)
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RA Gatenby, K Smallbone, PK Maini, F Rose, J Averill, RB Nagle, L Worrall, RJ Gillies (2007)
Cellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer.
Br. J. Cancer 97: 646-653 (doi)
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K Smallbone, RA Gatenby, RJ Gillies, PK Maini, DJ Gavaghan (2007)
Metabolic changes during carcinogenesis: Potential impact on invasiveness.
J. Theor. Biol. 244: 703-713 (doi)
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K Smallbone, DJ Gavaghan, RA Gatenby, PK Maini (2005)
The role of acidity in solid tumour growth and invasion.
J. Theor. Biol. 235: 476-484 (doi)
Links
Systems Biology Seminar Series page.
Oxford 4NCL website. |
