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A kinetic mechanism for cell sorting based on local variations in cell motility

Cell sorting.

Our current understanding of cell sorting relies on physical di fference, either in the interfacial properties or motile force, between cell types. But is such asymmetry a prerequisite for cell sorting? We test this using a minimal model in which the two cell populations are identical with respect to their physical properties and di erences in motility arise solely from how cells interact with their surroundings. The model resembles the Schelling model used in social sciences to study segregation phenomena at the scale of societies. Our results demonstrate that segregation can emerge solely from cell motility being a dynamic property that changes in response to the local environment of the cell, but that additional mechanisms are necessary to reproduce the envelopment behavior observed in vitro. The time course of segregation follows a power-law, in agreement with the scaling reported from experiment and in other models of motility-driven segregation.

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Asymmetric Segregation of Damaged Cellular Components in Spatially Structured Multicellular Organisms

Damage accumulation in a system of spatially ordered cells with symmetric and asymmetric replication, respectively.

The asymmetric distribution of damaged cellular components has been observed in species ranging from fission yeast to humans. To study the potential advantages of damage segregation, we have developed a mathematical model describing ageing mammalian tissue, that is, a multicellular system of somatic cells that do not rejuvenate at cell division. To illustrate the applicability of the model, we specifically consider damage incurred by mutations to mitochondrial DNA, which are thought to be implicated in the mammalian ageing process. We show analytically that the asymmetric distribution of damaged cellular components reduces the overall damage level and increases the longevity of the cell population. Motivated by the experimental reports of damage segregation in human embryonic stem cells, dividing symmetrically with respect to cell-fate, we extend the model to consider spatially structured systems of cells. Imposing spatial structure reduces, but does not eliminate, the advantage of asymmetric division over symmetric division. The results suggest that damage partitioning could be a common strategy for reducing the accumulation of damage in a wider range of cell types than previously thought.

The work was a collaboration with Jeppe Juul and Kristian Moss Bendtsen at Center for Models of Life, University of Copenhagen.

The article is available here.

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Novel electronic structures in elements under high pressure

An electride structure in an element at high pressure.

We used ’Ab initio random structure searching’ to study novel electronic structures in elements under extreme pressure. At multi-TPa pressures, certain elements are found to adopt an electride structure where valence electrons pile up in the interstitial regions. This signals a  breakdown of the nearly free electron model and necessitates an alternative theoretical description.

The work was carried out under the supervision of Professor Richard Needs and Professor Chris Pickard. Calculations were carried out on the Cambridge High Performance Computing Cluster Darwin.

 

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The competition between gravity and flow focusing in two-layered porous media

Geological storage options for carbon dioxide.

The gravitationally driven flow of a dense fluid within a two-layered porous media is examined experimentally and theoretically. We find that in systems with two horizontal layers of differing permeability a competition between gravity driven flow and flow focusing along high-permeability routes can lead to two distinct flow regimes. When the lower layer is more permeable than the upper layer, gravity acts along high- permeability pathways and the flow is enhanced in the lower layer. Alternatively, when the upper layer is more permeable than the lower layer, we find that for a sufficiently small input flux the flow is confined to the lower layer. However, above a critical flux fluid preferentially spreads horizontally within the upper layer before ultimately draining back down into the lower layer. This later regime, in which the fluid overrides the low-permeability lower layer, is important because it enhances the mixing of the two fluids. We show that the critical flux which separates these two regimes can be characterized by a simple power law. Finally, we briefly discuss the relevance of this work to the geological sequestration of carbon dioxide and other industrial and natural flows in porous media.

The paper is available here. The research was carried while I was at the Department of Applied Mathematics and Theoretical Physics in Cambridge.

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The role of ketone bodies in diabetic coma

Structure of the lipid membrane

Ketone bodies (acetone, acetoacetic acid, \beta-hydroxybutyric acid) are produced when the liver metabolizes fatty acids. If glucose is scarce, or if insulin levels are low, the brain relies on ketone bodies for energy. In patients with diabetes, a prolonged build up of ketone bodies may trigger a reversible comatose condition. This project explored the hypothesis that the accumulation of  ketone bodies in nerve cell membranes changes their physical properties and that this is the mechanism by which diabetic coma is induced. I used differential scanning calorimetry and monolayer techniques to study changes in the properties of model membrane systems upon addition of ketone bodies.The work was carried out at the Center for Biomembrane Physics under the supervision of Professor Ole G. Mouritsen.

The project was awarded first prize at the Danish Contest for Young Scientists in 2007, and I also received a travel grant to present the work at the Beijing Youth Science Creation Competition.

 

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A novel method for synthesizing N-methyl fluoxetine

The chemical structure of Fluoxetine

N-methyl Fluoxetine is a precursor for the antidepressant Fluoxetine (also known by the tradename Prozac). In this project, I combined theoretical observations with experimental work to develop a method for synthesizing N-methyl Fluoxetine that does not involve chemicals that present a biohazard. Consequently, the synthesis is safe enough to be carried out in a high school laboratory, has a reduced impact on the environment, and gives a comparable yield to the original method. The  main part of the project was carried out in the chemistry laboratory at Svendborg Technical High School. Analysis of the final product was done at the University of Southern Denmark.

The project was awarded first prize in the Danish Contest for Young Scientists, as well as in the EU Contest for Young Scientists, in 2004.