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MRes Student publishes on Current Biology
- MRes student Nils Gustafsson has contributed to a microtubule publication in prestigious journal Current Biology
CoMPLEX PhD student publishes on Science
This page lists the student talks that will take place during the conference. For talks whose author agreed to online publication, clicking the title will lead you to the abstract of the talk.
|Andrea||Dimitracopoulos||Mitotic rounding alters cell geometry to ensure efficient spindle assembly and positioning|
|Tharindi||Hapuarachchi||Modelling blood flow and metabolism in the neonatal brain|
|Zena||Hadjivasiliou||Dynamics of gamete chemotaxis in sexual reproduction|
|Charlie||Harrison||Rare and valuable: identifying rare codons that aid protein expression|
|David||Sheehan||Molecular Mechanisms Regulating GabaA Receptor Lateral Mobility In The Plasma Membrane|
|Niclas||Thomas||High throughput-sequencing of the T cell receptor repertoire as a biomarker for disease|
Mitotic rounding alters cell geometry to ensure efficient spindle assembly and positioning
To ensure the precise control of animal cell division orientation, it is important that changes in the structure of the microtubule-based spindle and the actin-based cell cortex be coordinated. Cells entering mitosis undergo dramatic geometrical changes dependent on re- organisation of the actin cytoskeleton, but it is still unknown whether the actin cortex plays a direct role in spindle assembly and positioning.
By studying the effects of a series of spindle and cell geometry perturbations this work reveals that as a result of the limited reach of mitotic centrosome-nucleated microtubules, cell rounding plays an essential role in spindle assembly and positioning. It provides a space in which efficient capture and congression of chromosomes can occur, and enhances the ability of astral microtubules to stably position the spindle.
These results explain why mitotic cell rounding is an almost universal process between animal cells.
Modelling blood flow and metabolism in the neonatal brain
Neonatal brain injury can result from hypoxia-ischaemia - reduced oxygen delivery and/or blood flow. This can occur due to complications either in the uterus or during delivery, frequently causing severe disabilities in these young patients.
Piglets are often used as models of human neonates for clinical experiments. We have created a computational model of blood flow and metabolism in the neonatal piglet brain to investigate hypoxia-ischaemia. Placing emphasis on the physiology of the brain, this model is an adaptation and extension of an earlier model of the adult human brain.
We use data from piglet experiments to help build and test the model, which is able to simulate near-infrared spectroscopy (NIRS) and magnetic resonance spectroscopy (MRS) measurements – two non-invasive methods that we use to estimate brain tissue oxygenation, haemodynamics and metabolism.
Our work aims to better understand the the metabolic and circulatory processes that occur during and in the aftermath hypoxia-ischaemia, and how they relate to subsequent injury severity. Since we directly simulate clinical measurements and incorporate clinical data from an early stage, we are able to attain more accurate and clinically relevant results, which may help inform clinicians on injury pathways and the best neuroprotective strategies and that can be used in such circumstances. In due course, the model will be adapted to the human neonatal brain.
Dynamics of gamete chemotaxis in sexual reproduction
The persistence of binary mating systems in sexual organisms constitutes a well-known conundrum in evolutionary biology. In the majority of sexual organisms two different types of gametes are necessary for reproduction. The role of this asymmetry is unclear. Although different organisms have evolved various means to reproduce sexually, there is a common underlying process where specialised sexual cells (the gametes) need to recognise each other and fuse. For this to successfully occur the two gametes need to recognise each other reach each other and effectively fuse. Therefore, communication between gametes is a vital aspect of the process. This is typically manifested via the generation and detection of chemical gradients. Various experimental reports suggest that gametes of different sex or mating type are attracted to each other via the release of and response to pheromones. What is more, the majority of these reports indicate that gametes of different type or sex take up different roles in this communication. In this work we investigate the significance of this asymmetric function and its relevance to the evolution of two sexes. We use mathematical modelling to explore the hypothesis that by being restricted to either secreting or releasing sexual pheromones the gametes achieve a more efficient mechanism of attraction whereby the speed at which they approach each other is optimised.
Rare and valuable: identifying rare codons that aid protein expression
The universal genetic code is a mapping between triplets of nucleotides (called codons) and amino acids. Different codons that are translated to the same amino acid by the ribosomal machinery are called “synonymous”. The code is constructed in such a way that all but two amino acids are encoded by groups of synonymous codons. How the various synonymous codons are selected is something of a mystery, but there is evident bias, with some being used more frequently than others. Furthermore, there is a correlation between codon usage frequencies and tRNA levels in the cell, suggesting a link with translation kinetics. Traditionally, when designing a recombinant gene, the strategy is to select the codons that are used most frequently by the target host organism. This has been shown to increase the rate of polypeptide production, but does not always lead to properly folded and functional proteins. I am identifying and investigating cases where rare codons appear to be selected preferentially over
more common ones and may be important for correct gene expression.
High throughput-sequencing of the T cell receptor repertoire as a biomarker for disease
With continuing improvements in high-throughput sequencing (HTS) facilitating broader, deeper coverage of the T cell receptor (TcR) repertoire than ever before, new avenues for data exploration are opened, affording the novel application of existing methodology to new areas of research. In theory, the TcR repertoire holds a wealth of knowledge, detailing both previous exposure to disease as well as the presence of any current infections. Thus, deep sequencing of the TcR repertoire can, theoretically, be utilised to probe the repertoire for signatures of infection and consequently be used as a diagnostic tool in clinical setttings.
Here, an approach that was originally conceived and developed in the field of computer vision and image recognition is adopted, to utilise the predictive power of support vector machines in conjunction with a high-resolution insight into the host's TcR repertoire, with the goal of stratifying murine, splenic TcR repertoire samples taken at different timepoints following OVA-immunization. The approach yields remarkably successful results, potentially laying the framework for future disease stratification using HTS of the TcR repertoire.
Page last modified on 03 may 13 17:43