Our research is conducted across six major areas and benefits from collaborations with a number of major organisations. The Mathematical Biology research group's key interests include pharmacology, cardiovascular health, tumour growth, bacterial chemotaxis, lipoprotein metabolism, and neuroscience and neurodynamics.
Cardiovascular health (Dr Marcus Tindall)
With Professor Jon Gibbins and his group and Dr Mike Fry at the University of Reading we are currently developing a model of the GPVI signalling pathway within a platelet following recent funding from the British Heart Foundation. This work is the first step in developing a more detailed model of platelet regulation in order to provide a theoretical tool for the future development of therapeutic strategies.
We are currently developing a number of collaborations with Prof Angela Clerk and her group at Reading which focuses on the role of specific signalling pathways (genetic to protein scale) affecting the development and function of cardiac myocytes.
Relevant selected publications
Giraldo, A., Barrett, O.P.T., Tindall, M.J., Fuller, S.J., Amirak, E.A, Bhattacharya, B.S., Sugden, P.H. and Clerk, A. Feedback regulation by Atf3 in the endothelin-1-responsive transcriptome in cardiomyocytes: Egr1 is a principal Atf3 target. Biochem. J., doi:10.1042/BJ20120125, 2012.
Bacterial chemotaxis (Dr Marcus Tindall)
This work is focused on developing mathematical models at the single cell and multicellular (biofilm) scale. In respect of single cells, we are interested in understanding intracellular signalling pathways within chemotactic bacteria. Chemotactic bacteria sense their external environment via a series of membrane bound receptors. Changes in the environment are communicated with the flagella driving the bacteria through its environment via series of biochemical pathways.
We have recently considered these pathways within the well studied system of Escherichia coli and the more complex system of Rhodobacter sphaeroides. This work is undertaken in collaboration with Prof Judy Armitage and her group at the Oxford Centre for Integrative Systems Biology.
Relevant selected publications
Kojadinovic, M., Armitage, J.P., Tindall, M.J. and Wadhams, G.H. Response kinetics in the complex chemotaxis signalling pathway of Rhodobacter sphaeroides. J. Royal. Soc. Interface, 10(81):20121001, 2013.
Tindall, M.J., Gaffney, E., Maini, P.K. and Armitage, J.P. Theoretical insights into bacterial chemotaxis (Invited Review). Wiley Interdiscip. Rev. Syst. Biol. Med, doi:10.1002/wsbm.1168., 2012.
Tindall, M.J., Porter, S.L., Maini, P.K. and Armitage, J.P. Modeling chemotaxis reveals the role of reversed phosphotransfer and a bi-functional phosphatase, PLoS Comput. Biol., 6(8), e1000896, 2010.
Lipoprotein metabolism (Dr Marcus Tindall)
Lipoproteins are the key mechanism by which dietary fats are transported around the body and broken down. Our work here, in collaboaration with members of the Institute for Cardiovascular and Metabolic Research at Reading, is focused on lipoprotein endocytosis (uptake) by hep and the delipidation pathway (the breakdown of lipoproteins into their constitute smaller particle types).
We have recently published a detailed mathematical model of the uptake of very low density lipoproteins (VLDL) and low density lipoproteins (LDL) and the competition between them for cell surface receptors and have recently completed work modelling the genetic regulation of cell surface receptors and cholesterol biosynthesis during LDL uptake.
Relevant selected publications
Tindall, M.J., Wattis, J.A.D., O'Malley, B., Pickersgill, L. and Jackson, K.G. A continuum receptor model of hepatic lipoprotein metabolism, J. Theor. Biol., 257(3), 371-84, 2009.
Bhattacharya, B.S., Sweby, P.K., Minihane, A., Jackson, K.G. and Tindall, M.J. A mathematical model of the sterol regulatory element binding protein 2 cholesterol biosynthesis pathway. J. Theor. Biol., 349:150-62, 2014.
Neuroscience and neurodynamics (Professor Roland Potthast)
Neural activity in the brain is the basis of human thinking, of emotions and actions, of human communication and interaction. Within the Centre of Integrative Neuroscience and Neurodynamics (CINN) an interdisciplinary team of researchers develops mathematical models which have the capability to link high-level mental processes like language understanding and processing with neural activities.
In cooperation with partners from linguistics, the way humans use and process language is investigated with models on different levels. This includes neural field models, which describe the activity of large quantities of neurons by fields in space and time. Within recent grants integrated models for neural activity are under development, which include the physical and chemical processes in the brain as well as the electrical activity which is usually modelled by neural network approaches.
The team also develops measurement approaches including the integrated use of MRI, EEG and ODT, where models are explored in field studies on humans. Further work is carried out on living neural cultures, where approaches can be tested in a small-scale well-defined environment.
Relevant selected publications
Dimensional reduction for the inverse problem of neural field theory. Potthast, R and Graben, P.B. Front., Comput. Neurosci. 3(17). doi: 10.3389/neuro.10.017, 2009.
On the spectra of certain integro-differential-delay problems with applications in neurodynamics. Grindrod, P. and Pinotsis, D., Physica D: Nonlinear Phenomena, 240 (1), 2010.
Systems pharmacology (Dr Marcus Tindall)
We are currently working with Pfizer and members of the Leiden Academic Center for Drug Research on model reduction methods for large scale systems biology networks. The goal here is to be able to link between the lower scale intracellular signalling models and higher scale pharmacodynamics pharmacokinetic (PKPD) models of drug metabolism and delivery. This is new, ongoing work and publications from current research will be listed here when available.
Tumour modelling (Dr Marcus Tindall)
This follows on from earlier work that has focused on population models of multicellular tumour spheroids (3D in vitro cell aggregates which mimic many of the characteristics of in vivo tumours), which incorporates a simple cell cycle model and description of cell movement. We have recently published a model which brings together the role of acidosis in tumours on their cell cycle state structure.
Relevant selected publications
Tindall, M.J., Dyson, L., Smallbone, K. and Maini, P.K.Modelling Acidosis and the Cell Cycle in Multicellular Tumour Spheroids. J. Theor. Biol., 298, 107-115, 2012.
Murray, P.J., Walter, A., Edwards, C.M., Tindall, M.J. and Maini, P.K. Comparing a discrete and continuum model of the intestinal crypt. Phys. Biol., 8(2), 026011, 2011.
