Congratulations to Linus!

(Belated) congratulations to Linus (@LinusSchumacher) on being granted leave to supplicate for his D.Phil.!

Linus’ thesis explores the role of collective cell migration and self-organisation in the development of the embryo and in vitro tissue formation through mathematical and computational approaches. We consider how population heterogeneity, microenvironmental signals and cell-cell interactions facilitate cells to collectively organise and navigate, with the aim to work towards uncovering general rules and principles, rather than delving into the microscopic molecular details. To ensure the biological relevance of our results, we collaborate closely with experimental biologists working on two model systems.

Publications include:

  • R. McLennan, L. J. Schumacher, J. A. Morrison, J. M. Teddy, D. A. Ridenour, A. C. Box, C. L. Semerad, H. Li, W. McDowell, D. Kay, P. K. Maini, R. E. Baker and P. M. Kulesa (2015). Neural crest migration is driven by a few trailblazer cells with a unique molecular signature narrowly confined to the invasive front. Development 142:2014-2025. DOI
  • R. McLennan, L. J. Schumacher, J. A. Morrison, J. M. Teddy, D. A. Ridenour, A. C. Box, C. L. Semerad, H. Li, W. McDowell, D. Kay, P. K. Maini, R. E. Baker and P. M. Kulesa (2015). VEGF signals induce trailblazer cell identity that drives neural crest migration. Dev. Biol. 407(1):12-25. DOI

PhD studentship opportunity at the University of Bath

PhD studentship opportunity at the University of Bath.

Cross-disciplinary investigation of pattern formation in Zebrafish using spatially extended mathematical models with volume exclusion
http://www.findaphd.com/search/ProjectDetails.aspx?PJID=67118&LID=69

Supervisors:

Dr Christian Yates (Mathematical Sciences, University of Bath),
Professor Ruth Baker (Mathematics, University of Oxford),
Professor Robert Kelsh (Biology and Biochemistry, University of Bath).

Description:

Pigment pattern formation – the process generating functional and often beautiful distributions of pigment cells in the skin – represents a classic problem in pattern formation. Pigment pattern formation in adult zebrafish is now one of the best-studied examples. Three cell types are known to contribute to the striped pigment patterns of zebrafish; xanthophores, melanophores and iridophores. We have also recently identified Agouti Signalling Peptide (ASIP) as a further patterning component. Traditionally zebrafish pattern modelling has been conducted at the continuum level with Turing instability the proposed mechanism. However, the discrete nature of the agents (cells) involved suggests that individual-based models might be preferable, to allow inclusion of biological noise and to account for the finite volume of the cells.

Under the supervision of leading experts in stochastic mathematical modelling and developmental biology of pattern formation the student will generate a versatile framework to investigate the effects of stochasticity and finite cell size upon pattern formation models which include all cell-types and ASIP signalling. This model will be informed by the experimental data on zebrafish skin patterning. Biological predictions of the model will then be tested experimentally and the findings used to feedback into the model as part of an iterative model-development cycle.

In particular, the student will construct an on-lattice exclusion-process model in which cells interact with neighbours, and move to neighbouring lattice sites. A detailed investigation of the relationship between key length scales in the model, the system size and compartment size, and their impact on the patterns formed, will be carried out. Subsequently hypotheses on pigment cell interactions will be explicitly encoded into this framework to explore the potential of the model to replicate the patterns of both wild-type and mutant fish.

Guided by the modelling outputs, the student will generate data to test the models’ efficacy. Data will be obtained from the literature and targeted experimental studies. Experimental studies will include direct quantitative measurements of important properties of the pigment cell pattern, e.g. dynamic cell-cell distances and density; pair-correlation functions; and gene expression (e.g. using qRT-PCR) in skin samples at different stages.

The student selected for this project will develop invaluable skill sets in both mathematical modelling and experimental genetics and cell biology whilst also making a significant contribution to the
understanding of a canonical biological pattern formation system. These mixed skill sets will make the candidate a highly desirable recruitment prospect for future employers.

Reconciling transport models across scales

Our manuscript “Reconciling transport models across scales: the role of volume exclusion” with , and has just been accepted for publication as a Rapid Communication in Physical Review E! You can find a draft of our manuscript on the arXiv.

IWH-Symposium on Collective Cell Migration and my first attempt at figshare

Just back from the excellent IWH-Symposium on Collective Cell Migration organised by Ulrik Schwartz, Freddy Frischknecht and Heike Bohm.

I had my first attempt at publishing my talk using figshare too! You can find my talk using this DOI.

Welcome to Jonathan Harrison!

Excited to welcome Jonathan Harrison to the group for his 12-week DTC project!

Jonathan will be working joint with the groups of Ilan Davis in Biochemistry and Jens Rittscher in the Institute of Biomedical Engineering to explore mechanisms for mRNA localisation.

Congratulations to Graham!

Congratulations to Graham for passing his viva on Friday!

Parameter recovery in AC solution-phase voltammetry and a consideration of some issues arising when applied to surface-confined reactions

A major problem in the quantitative analysis of AC voltammetric data has been the variance in results between laboratories, often resulting from a reliance on “heuristic” methods of parameter estimation that are strongly dependent on the choices of the operator. In this thesis, an automatic method for parameter estimation will be tested in the context of experiments involving electron-transfer processes in solution-phase. It will be shown that this automatic method produces parameter estimates consistent with those from other methods and the literature in the case of the ferri-/ferrocyanide couple, and is able to explain inconsistency in published values of the rate parameter for the ferrocene/ferrocenium couple. When a coupled homogeneous reaction is considered in a theoretical study, parameter recovery is achieved with a higher degree of accuracy when simulated data resulting from a high frequency AC voltammetry waveform are used.

When surface-confined reactions are considered, heterogeneity in the rate constant and formal potential make parameter estimation more challenging. In the final study, a method for incorporating these “dispersion” effects into voltammetric simulations is presented, and for the first time, a quantitive theoretical study of the impact of dispersion on measured current is undertaken.

You can find papers arising from his work here:

  1. G. P. Morris, A. N. Simonov, E. A. Mashkina, R. Bordas, K. Gillow, R. E. Baker, D. J. Gavaghan and A. M. Bond (2013). A comparison of fully automated methods of data analysis and computer assisted heuristic methods in an electrode kinetic study of the pathologically variable [Fe(CN)6]3- /4- process by AC voltammetry. Anal. Chem. 85(24):11780–11787. DOI
  2. A. N. Simonov, G. P. Morris, E. A. Mashkina, B. Bethwaite, K. Gillow, R. E. Baker, D. J. Gavaghan and A. M. Bond (2014). Inappropriate use of the quasi-reversible electrode kinetic model in simulation-experiment comparisons of voltammetric processes that approach the reversible limit. To appear in Anal. Chem. DOI

Congratulations to Debbie!

Congratulations to Debbie on passing her viva on Wednesday!

Spatial correlation models for cell populations
Determining the emergent behaviour of a population from the interactions of its individuals is an ongoing challenge in the modelling of biological phenomena. Many classical models assume that the spatial location of each individual is independent of the locations of all other individuals. This mean-field assumption is not always realistic; in biological systems we frequently see clusters of individuals develop from uniform initial conditions. In this thesis, we explore situations in which the mean-field approximation is no longer valid for volume-excluding processes on a regular lattice. We provide methods which take into account the spatial correlations between lattice sites, thus more accurately reflecting the system’s behaviour, and discuss methods which can provide information as to the validity of mean-eld and other approximations.

You can check out the papers arising from her work here:

  1. D. C. Markham, M. J. Simpson and R. E. Baker (2013). Simplified method for including spatial correlations in mean-field approximations. Phys. Rev. E 87(6):062702. DOI
  2. D. C. Markham, M. J. Simpson, P. K. Maini, E. A. Gaffney and R. E. Baker (2013). Incorporating spatial correlations into multispecies mean-field models. Phys. Rev. E 88(5):052713. DOI
  3. D. C. Markham, M. J. Simpson, P. K. Maini, E. A. Gaffney and R. E. Baker (2014). Comparing methods for modelling spreading cell fronts. J. Theor. Biol. 353:95-103. DOI
  4. D. C. Markham, M. J. Simpson and R. E. Baker (2014). Choosing an appropriate framework for analysing multispecies co-culture experiments. Available on bioRxiv. DOI