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Professor Markus Owen

Professor of Mathematical Biology, Faculty of Science

Contact

  • workRoom C5 The Mathematical Sciences Building
    University Park
    Nottingham
    NG7 2RD
    UK
  • work0115 8467214
  • fax0115 9514951

Biography

Macrogen animation

  • BSc Applied Mathematics, Warwick, 1994 (1st class)
  • PhD Interdisciplinary Applied Mathematics, Warwick, 1997 (supervisor, Jonathan Sherratt)
  • PDRA, University of Utah, 1997-1999
  • Lecturer, Loughborough University, 1999-2003; Senior Lecturer, 2003-2004
  • Reader, University of Nottingham, 2004-2013
  • Professor of Mathematical Biology, 2013-date

Teaching Summary

Modules

I am particularly interested in how to deliver mathematical modelling concepts to life scientists.

Research Summary

From 2011 to 2019 I was Head of the Mathematical Medicine and Biology Research Group and Director of the Centre for Mathematical Medicine and Biology.

From 2015 to 2022 I led a Leverhulme Doctoral Scholarships programme in Modelling and Analytics for a Sustainable Society. Going further back, I led the BBSRC-funded Multiscale Biology Network and the EPSRC-funded Cell Signalling Network (Signet).

Google Scholar | Nottingham ePrints | ORCiD | ResearcherID | Twitter @MarkusOwenMMB | LMS Directory

Current PhD students: Nicholas Harbour

Previous PhD students:

Previous PDRAs: Lloyd Bridge, Jenn Gaskell, Yue Hu, Alistair Middleton, Stephen Pring, Johanna Stamper, Steve Webb and Hao Zhu

My principal research interests are in the application of nonlinear mathematical models to problems in cell biology, in particular to cancer, angiogenesis (the growth of new blood vessels), developmental biology (both in animals and plants) and neuroscience. I also have an interest in ecology and immunology. I use a variety of mathematical approaches, including models for single cells, populations and tissues, and a range of tools for mathematical analysis and computer simulation. Much of this work is underpinned by multidisciplinary collaborations with life scientists, engineers, computer scientists and other mathematicians.

Selected Publications

The Centre for Mathematical Medicine and Biology (CMMB) is based within the School of Mathematical Sciences and comprises members of the University of Nottingham who use mathematical methods to provide insights into biological and biomedical phenomena. We aim to promote the application of mathematical modelling to medicine and the biomedical sciences, and to stimulate multi-disciplinary research within the University and beyond

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Past Research

MODELLING THE MACROPHAGE INVASION OF TUMOURS

Even in the early stages of their development, tumours are not simply a homogeneous grouping of mutant cells; rather, they develop in tandem with normal tissue cells, and also recruit other cell types. Many solid tumours contain a high proportion of macrophages, a type of white blood cell which can have a variety of effects upon the tumour, leading to a delicate balance between growth promotion and inhibition.

ODE model for macrophage-tumour interactions: Initial research concentrated on an ODE model for the anti-tumour effects of macrophages, a type of white blood cell, and results show that while macrophages can strongly affect the cellular composition of a tumour, they cannot eliminate it altogether. Inclusion in this model of a source term of chemical regulator, corresponding to some immuno-therapeutic strategies targeting macrophages, was shown to lead to the possibility of tumour regression. A detailed bifurcation analysis demonstrated the possibility of multiple stable steady states and hysteresis.

Immunotherapy simulation Immunotherapy simulation (jpeg).

PDE model -- pattern formation: Tumour growth is very much a spatial phenomenon, and so the natural next step was to include spatial variation. In the consequent PDE model, random cell movement and diffusion of a chemical regulator lead to a pattern forming bifurcation behind a travelling wave front of invading tumour cells. This is explained by the rapid diffusion of chemical regulator leading to a typical long range activation---short range inhibition type mechanism. These results suggest that tumour heterogeneity may arise in part as a consequence of macrophage infiltration.

MIN=RED<-----MACROPHAGE DENSITY----->GREEN=MAX

2d simulation showing evolution of a pattern behind a travelling wave of tumour invasion.

Explanation of patterningAn intuitive explanation for this spatial instability is that given a local perturbation increasing the density of mutant cells, chemical regulator production will also increase locally. Then if the chemical diffuses fast enough, it will act non-locally to activate macrophages to the tumouricidal state and to stimulate an additional influx of macrophages. This will suppress non-local mutant cell growth, whilst enhancing local mutant cell growth, due to the relative suppression of local macrophage activation, so that the original perturbation will grow in time.

Solutions are irregular in space and timePDE model -- spatiotemporal irregularity: Using data from the literature I determined ranges for the parameters governing macrophage motility using a mathematical model of the experimental procedure. Including macrophage chemotaxis with these parameters led to the development of irregular wakes behind the wave front of invading tumour cells. This phenomenon was investigated using domain length as a bifurcation parameter. Stable oscillating solutions with a regular period were found to coexist with stable steady patterns for certain windows in domain length which were deduced to appear at regular intervals. Intuitively the wave front can be treated as a moving boundary, leading to the proposal that as the wave spreads out, the effective domain length passes through a series of bifurcations, so that the solution seen is always transient and irregular.

MIN=RED<-----MACROPHAGE DENSITY----->GREEN=MAXSnapshots from a two-dimensional simulation illustrating that chemotaxis leads to solutions which are irregular in space and time. For a movie of a similar simulation, click here: Chemotaxis induces spatiotemporal irregularities (mpeg) and another example (mpeg).

Future Research

Future research will continue to focus on many of the above topics. For PhD opportunities, see:

https://www.nottingham.ac.uk/mathematics/study/research/postgraduate-projects.aspx

World-class research at the University of Nottingham

University Park
Nottingham
NG7 2RD
+44 (0) 115 951 5151
research@nottingham.ac.uk
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