BIOMEDICAL & CLINICAL APPLICATIONS
CARDIOVASCULAR CELL BIOLOGY
With Prof 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 steps in developing a more detailed model of platelet regulation in order to provide a theoretical tool for the future development of therapeutic strategies.
- 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.
CELL SIGNALLING PATHWAYS
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.
- 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.
CHOLESTEROL & LIPOPROTEIN METABOLISM
Lipoproteins are the key mechanism by which dietary fats are transported around the body and breakdown by it. Cholesterol is both produced by the body as well as a constitute of the everyday diet. At Reading we have created a series of mathematical models which describe these processes, both independently and in an integrated manner. We are focused on the role of cholesterol regulation in a variety of contexts, with both biomedical, nutritional and clinical applications in mind.
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.
QUANTITATIVE SYSTEMS PHARMACOLOGY
NEUROSCIENCE AND NEURODYNAMICS
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 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.