Dr Alexander Fletcher
School of Mathematics and Statistics
+44 114 222 3846
Full contact details
School of Mathematics and Statistics
- 2022 - present: Senior Lecturer, School of Mathematics and Statistics, University of Sheffield
- 2019 - 2022: Lecturer, School of Mathematics and Statistics, University of Sheffield
- 2015 - 2019 : Vice-Chancellor's Fellow, School of Mathematics and Statistics, University of Sheffield
- 2011 - 2015 : Research Fellow in Computational Science, Mathematical Institute, University of Oxford
- 2008 - 2015 : Stipendiary Lecturer in Mathematics, St Hugh's College, University of Oxford
- 2008 - 2011 : Postdoctoral Research Assistant, Mathematical Institute, University of Oxford
- 2005 - 2010 : DPhil, Mathematical Institute, University of Oxford
- Research interests
I develop and apply mathematical models to study complex biological systems. Techniques range from discrete and continuous models of temporal dynamics to more computationally intensive individual-based and multiscale simulations. Major applications include mechanisms underlying tissue homeostasis and their disruption in cancer formation and progression, and the orchestration of cell-level processes such as proliferation, death, adhesion and migration to give correct tissue-level proportions in embryos.
This person does not have any publications available.
- ChemChaste : simulating spatially inhomogeneous biochemical reaction–diffusion systems for modeling cell–environment feedbacks. GigaScience, 11(2022).
- Adhesion-regulated junction slippage controls cell intercalation dynamics in an Apposed-Cortex Adhesion Model. PLoS Computational Biology, 18(1).
- The evolution of strategy in bacterial warfare via the regulation of bacteriocins and antibiotics. eLife, 10.
- Modelling of epithelial growth, fission and lumen formation during embryonic thyroid development : a combination of computational and experimental approaches. Frontiers in Endocrinology, 12.
- Seven challenges in the multiscale modeling of multicellular tissues. WIREs Mechanisms of Disease. View this article in WRRO
- Of mitogens and morphogens : modelling Sonic Hedgehog mechanisms in vertebrate development. Philosophical Transactions of the Royal Society B: Biological Sciences, 375(1809).
- Contemporary morphogenesis: Contemporary morphogenesis. Philosophical Transactions of the Royal Society B: Biological Sciences, 375(1809).
- Toward engineering biosystems with emergent collective functions. Frontiers in Bioengineering and Biotechnology, 8. View this article in WRRO
- Coupled differentiation and division of embryonic stem cells inferred from clonal snapshots. Physical Biology. View this article in WRRO
- Close encounters of the cell kind: The impact of contact inhibition on tumour growth and cancer models. Bulletin of Mathematical Biology, 82(2). View this article in WRRO
- Cross-talk between Hippo and Wnt signalling pathways in intestinal crypts : insights from an agent-based model. Computational and Structural Biotechnology Journal, 18, 230-240. View this article in WRRO
- The tricellular vertex-specific adhesion molecule sidekick facilitates polarised cell intercalation during drosophila axis extension. PLOS Biology, 17(12). View this article in WRRO
- Conserved gene signalling and a derived patterning mechanism underlie the development of avian footpad scales. EvoDevo, 10(1). View this article in WRRO
- Inferring tumour proliferative organisation from phylogenetic tree measures in a computational model. Systematic Biology, 0, 1-41. View this article in WRRO
- The devil is in the mesoscale: Mechanical and behavioural heterogeneity in collective cell movement. Seminars in Cell and Developmental Biology, 93, 46-54. View this article in WRRO
- Experimental and theoretical evidence for bidirectional signaling via core planar polarity protein complexes in Drosophila. iScience, 17, 49-66. View this article in WRRO
- Quantification of crypt and stem cell evolution in the normal and neoplastic human colon. Cell Reports, 27(8), 2524-2524. View this article in WRRO
- Recasting the Cancer Stem Cell Hypothesis: Unification Using a Continuum Model of Microenvironmental Forces. Current Stem Cell Reports, 5(1), 22-30. View this article in WRRO
- Elevated apoptosis impairs epithelial cell turnover and shortens villi in TNF-driven intestinal inflammation. Cell Death & Disease, 10. View this article in WRRO
- Tissue tension and not interphase cell shape determines cell division orientation in the Drosophila follicular epithelium. EMBO Journal, 38(3). View this article in WRRO
- An ancient Turing-like patterning mechanism regulates skin denticle development in sharks. Science Advances, 4(11). View this article in WRRO
- Chronic TNFα-driven injury delays cell migration to villi in the intestinal epithelium.. Interface, 15(145). View this article in WRRO
- Bayesian inference of agent-based models: a tool for studying kidney branching morphogenesis. Journal of Mathematical Biology, 76(7), 1673-1697. View this article in WRRO
- Approximate Bayesian computation reveals the importance of repeated measurements for parameterising cell-based models of growing tissues.. Journal of Theoretical Biology, 443, 66-81. View this article in WRRO
- Numerical Analysis of the Immersed Boundary Method for Cell-Based Simulation. SIAM Journal on Scientific Computing, 39(5), B943-B967. View this article in WRRO
- Integrating planar polarity and tissue mechanics in computational models of epithelial morphogenesis. Current Opinion in Systems Biology, 5, 41-49. View this article in WRRO
- Impact of implementation choices on quantitative predictions of cell-based computational models. Journal of Computational Physics, 345, 752-767. View this article in WRRO
- A hierarchical Bayesian model for understanding the spatiotemporal dynamics of the intestinal epithelium. PLoS Computational Biology, 13(7). View this article in WRRO
- Morphological Plant Modeling: Unleashing Geometric and Topological Potential within the Plant Sciences. Frontiers in Plant Science, 8. View this article in WRRO
- Mechanocellular models of epithelial morphogenesis. Philosophical Transactions of the Royal Society B: Biological Sciences, 372(1720). View this article in WRRO
- Comparing individual-based approaches to modelling the self-organization of multicellular tissues.. PLoS Computational Biology, 13(2). View this article in WRRO
- An extended model for culture-dependent heterogenous gene expression and proliferation dynamics in mouse embryonic stem cells. npj Systems Biology and Applications, 3(1). View this article in WRRO
- Robust cell tracking in epithelial tissues through identification of maximum common subgraphs. Interface, 13(124). View this article in WRRO
- Unipolar distributions of junctional Myosin II identify cell stripe boundaries that drive cell intercalation throughout Drosophila axis extension. eLife, 5. View this article in WRRO
- A Computational Modeling Approach for Deriving Biomarkers to Predict Cancer Risk in Premalignant Disease. Cancer Prevention Research, 9(4), 283-295. View this article in WRRO
- Multiscale modelling of intestinal crypt organization and carcinogenesis. Mathematical Models and Methods in Applied Sciences, 25(13), 2563-2585. View this article in WRRO
- Migration and horizontal gene transfer divide microbial genomes into multiple niches. Nature Communications, 6(1). View this article in WRRO
- Steering Evolution with Sequential Therapy to Prevent the Emergence of Bacterial Antibiotic Resistance. PLoS Computational Biology, 11(9). View this article in WRRO
- A parallel implementation of an off-lattice individual-based model of multicellular populations. Computer Physics Communications, 192, 130-137. View this article in WRRO
- Models, measurement and inference in epithelial tissue dynamics. Mathematical Biosciences and Engineering, 12(6), 1321-1340. View this article in WRRO
- Oxygen consumption dynamics in steady-state tumour models. Royal Society Open Science, 1(1), 140080-140080. View this article in WRRO
- Quantification of Crypt and Stem Cell Evolution in the Normal and Neoplastic Human Colon. Cell Reports, 8(4), 940-947.
- Modelling and analysis of bacterial tracks suggest an active reorientation mechanism in Rhodobacter sphaeroides. Journal of The Royal Society Interface, 11(97), 20140320-20140320.
- Vertex Models of Epithelial Morphogenesis. Biophysical Journal, 106(11), 2291-2304.
- Metabolic Alterations During the Growth of Tumour Spheroids. Cell Biochemistry and Biophysics, 68(3), 615-628.
- A filter-flow perspective of haematogenous metastasis offers a non-genetic paradigm for personalised cancer therapy. European Journal of Cancer, 50(17), 3068-3075.
- Implementing vertex dynamics models of cell populations in biology within a consistent computational framework. Progress in Biophysics and Molecular Biology, 113(2), 299-326.
- Mechanisms and mechanics of cell competition in epithelia. Nature Reviews Molecular Cell Biology, 14(9), 581-591.
- The effect of sampling rate on observed statistics in a correlated random walk. Journal of the Royal Society Interface, 10(85).
- Toward a quantitative understanding of the Wnt/β -catenin pathway through simulation and experiment. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 5(4), 391-407.
- A theoretical investigation of the effect of proliferation and adhesion on monoclonal conversion in the colonic crypt. Journal of Theoretical Biology, 312, 143-156.
- A PHABULOSA/Cytokinin Feedback Loop Controls Root Growth in Arabidopsis. Current Biology, 22(18), 1699-1704.
- Mathematical modeling of monoclonal conversion in the colonic crypt. Journal of Theoretical Biology, 300, 118-133.
- Modelling the role of the basement membrane beneath a growing epithelial monolayer. Journal of Theoretical Biology, 298, 82-91.
- Comparing a discrete and continuum model of the intestinal crypt. Physical Biology, 8(2), 026011-026011.
- A hybrid approach to multi-scale modelling of cancer. Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, 368(1930), 5013-5028.
- An integrative computational model for intestinal tissue renewal. Cell Proliferation, 42(5), 617-636.
- Chaste: A test-driven approach to software development for biological modelling. Computer Physics Communications, 180(12), 2452-2471.
- Spatial Metrics of Tumour Vascular Organisation Predict Radiation Efficacy in a Computational Model. PLOS Computational Biology, 12(1), e1004712-e1004712. View this article in WRRO
- Capabilities and Limitations of Tissue Size Control through Passive Mechanical Forces. PLOS Computational Biology, 11(12), e1004679-e1004679. View this article in WRRO
- Patterning of wound-induced intercellular Ca2+flashes in a developing epithelium. Physical Biology, 12(5), 056005-056005. View this article in WRRO
- Evidence of a role for radiation-induced lysosomal damage in non-targeted effects: an experimental and theoretical analysis.
- Capabilities and Limitations of Tissue Size Control Through Passive Mechanical Forces.
- Ten Simple Rules for a Successful Cross-Disciplinary Collaboration. PLOS Computational Biology, 11(4), e1004214-e1004214. View this article in WRRO
- Modelling and analysis of bacterial tracks suggest an active reorientation mechanism inRhodobacter sphaeroides.
- Ten Simple Rules for Effective Computational Research. PLoS Computational Biology, 10(3), e1003506-e1003506. View this article in WRRO
- Novel Methods for Analysing Bacterial Tracks Reveal Persistence in Rhodobacter sphaeroides. PLoS Computational Biology, 9(10), e1003276-e1003276. View this article in WRRO
- Chaste: An Open Source C++ Library for Computational Physiology and Biology. PLoS Computational Biology, 9(3), e1002970-e1002970. View this article in WRRO
- A computational study of discrete mechanical tissue models. Physical Biology, 6(3), 036001-036001.
- MultiCellDS: a community-developed standard for curating microenvironment-dependent multicellular data. View this article in WRRO
- Cell proliferation within small intestinal crypts is the principal driving force for cell migration on villi. FASEB Journal. View this article in WRRO
- Mathematical Modeling of the Metastatic Process, Experimental Metastasis: Modeling and Analysis (pp. 189-208). Springer Netherlands
- Multiscale Cancer Modeling CRC Press
Conference proceedings papers
- Research group
Current grants, as Principal Investigator: Understanding self-organised tissue patterning across scales EPSRC Chaste: developing sustainable software for computational biology BBSRC Current grants, as Coinvestigator: Hypothalamic development from self-organising progenitors Wellcome Trust Past grants, as Coinvestigator: How do the atypical cadherins Fat and Dachsous integrate growth and patterning during development? BBSRC
- Teaching activities
Mathematical Investigation Skills
MAS286 Mathematics and Statistics in Action