Past Mathematical Biology and Ecology Seminar

I will discuss two topics. Firstly, coupling of the circadian clock and cell cycle in mammalian cells. Together with the labs of Franck Delaunay (Nice) and Bert van der Horst (Rotterdam) we have developed a pipeline involving experimental and mathematical tools that enables us to track through time the phase of the circadian clock and cell cycle in the same single cell and to extend this to whole lineages. We show that for mouse fibroblast cell cultures under natural conditions, the clock and cell cycle phase-lock in a 1:1 fashion. We show that certain perturbations knock this coupled system onto another periodic state, phase-locked but with a different winding number. We use this understanding to explain previous results. Thus our study unravels novel phase dynamics of 2 key mammalian biological oscillators. Secondly, I present a radical revision of the Nrf2 signalling system. Stress responsive signalling coordinated by Nrf2 provides an adaptive response for protection against toxic insults, oxidative stress and metabolic dysfunction. We discover that the system is an autonomous oscillator that regulates its target genes in a novel way.

The majority of epidemic models fall into two categories: 1) deterministic models represented by differential equations and 2) stochastic models which can be evaluated by simulation. In this presentation I will discuss the precise connection between these models. Until recently, exact correspondence was only established in situations exhibiting large degrees of symmetry or for infinite populations.

I will consider SIR dynamics on finite static contact networks. I will give an overview of two provably exact deterministic representations of the underlying stochastic model for tree-like networks. These are the message passing description of Karrer and Newman and my pair-based moment closure representation. I will discuss relationship between the two representations and the relative merits of both.

Recent years have seen rapid expansion of the capabilities 
to recreate in vivo conditions using in vitro microfluidic assays.  
A wide range of single cell and cell population behaviors can now 
be replicated, controlled and imaged for detailed studies to gain 
new insights.  Such experiments also provide useful fodder for 
computational models, both in terms of estimating model parameters 
and for testing model-generated hypotheses.  Our experiments have 
focused in several different areas.  
1) Single cell migration experiments in 3D collagen gels have 
revealed that interstitial flow can lead to biased cell migration 
in the upstream direction, with important implications to cancer 
invasion.  We show this phenomenon to be a consequence of 
integrin-mediated mechanotransduction.  
2) Endothelial cells seeded in fibrin gels form perfusable 
vascular networks within 2-3 days through a process termed 
“vasculogenesis”.  The process by which cells sense their 
neighbours, extend projections and form anastomoses, and 
generate interconnected lumens can be observed through time-lapse 
microscopy.  
3) These vascular networks, once formed, can be perfused with 
medium containing cancer cells that become lodged in the 
smaller vessels and proceed to transmigrate across the endothelial 
barrier and invade into the surrounding matrix.  High resolution 
imaging of this process reveals a fascinating sequence of events 
involving interactions between a tumour cell, endothelial cells, 
and underlying matrix.  These three examples will be presented 
with a view toward gaining new insights through computational 
modelling of the associated phenomena.

Please see http://www.cs.ox.ac.uk/seminars/CompBioPublicSeminars/

Please see http://www.cs.ox.ac.uk/seminars/CompBioPublicSeminars/

Mechanics plays an important role during several biological phenomena such as morphogenesis,

wound healing, bone remodeling and tumorogenesis. Each one of these events is triggered by specific

elementary cell deformations or movements that may involve single cells or populations of cells. In

order to better understand how cell behave and interact, especially during degenerative processes (i.e.

tumorogenesis and metastasis), it has become necessary to combine both numerical and experimental

approaches. Particularly, numerical models allow determining those parameters that are still very

difficult to experimentally measure such as strains and stresses.

During the last few years, I have developed new finite element models to simulate morphogenetic

movements in Drosophila embryo, limb morphogenesis, bone remodeling as well as single and

collective cell migration. The common feature of these models is the multiplicative decomposition of

the deformation gradient which has been used to take into account both the active and the passive

deformations undergone by the cells. I will show how this mechanical approach, firstly used in the

seventies by Lee and Mandel to describe large viscoelastic deformations, can actually be very

powerful in modeling the biological phenomena mentioned above.

In this talk I will discuss recent developments in information theoretical approaches to fundamental

molecular processes that affect the cellular decision making processes. One of the challenges of applying

concepts from information theory to biological systems is that information is considered independently from

meaning. This means that a noisy signal carries quantifiably more information than a unperturbed signal.

This has, however, led us to consider and develop new approaches that allow us to quantify the level of noise

contributed by any molecular reactions in a reaction network. Surprisingly this analysis reveals an important and hitherto

often overlooked role of degradation reactions on the noisiness of biological systems. Following on from this I will outline

how such ideas can be used in order to understand some aspects of cell-fate decision making, which I will discuss with

reference to the haematopoietic system in health and disease.

The operation of sub-cellular processes in living organisms often require the transfer of biopolymers across impermeable lipid membranes. The emergence of new experimental techniques for manipulation of single molecules at nanometer scales have made possible in vitro experiments that can directly probe such translocation processes in cells as well as in synthetic systems. Some of these ideas have spawned novel bio-technologies with many more likely to emerge in the near future. In this talk I would review some of these experiments and attempt to provide a quantitative understanding of the data in terms of physical laws, primarily mechanics and electrostatics.

Please note that this is a joint seminar with the William Dunn School of Pathology and will be held in the EPA Seminar Room

*Please note that this is a joint seminar with the William Dunn School of Pathology and will take place in EPA Seminar Room which is located inside the Sir William Dunn School of Pathology and must be entered from the main entrance on South Parks Road. Link http://g.co/maps/8cbbx

Please note that this is a joint seminar with the William Dunn School of Pathology and will take place in the EPA Seminar Room, which is located inside the Sir William Dunn School of Pathology and must be entered from the main entrance on South Parks Road. link: http://g.co/maps/8cbbx

PLEASE NOTE THAT THIS SEMINAR HAS BEEN CANCELLED DUE TO ILLNESS.