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Stuart McHattie

Personal

Born in Kent, the Garden of England, I am a 29 year old postgraduate student at the University of Warwick. I am studying Systems Biology in the purpose built doctoral training centre funded by the EPSRC. Last year I completed an MSc in Systems Biology and I have now progressed onto a PhD in which I am studying senescence processes in Arabidopsis thaliana using data from a highly replicated microarray dataset and several bioinformatics techniques.

My Background

In September of 2000 I started my higher education career at the University of Liverpool, studying BSc Zoology with Honours. I completed a dissertation entitled "Analysis of Data on Dispersal of Southern Damselfly (Coenagrion mercuriale)" in which I analysed over 17,000 mark, release, recapture observations in Hampshire using Excel and a number of macros written by myself. The work I completed was way beyond the expectations of my supervisor and as such he recommended me for an MSc in Bioinformatics and employed me for a short period after my degree to complete some extra tasks he knew I would be capable of. The dissertation can be downloaded here.

Following the advice given to me by my supervisor at Liverpool, I applied for an MSc in Bioinformatics at De Montfort University in Leicester. During the course, I learnt a lot about the way in which computing can be used to augment research, particularly in the field of genetics. The information I learnt here lead me to complete a dissertation entitled "Where Do Proteins Come From: Evolve or be Lost? Analysis of an undescribed gene encoding a hybrid proline-rich protein in sugar beet (Beta vulgaris)". During this I studied the DNA sequence of the gene which encodes for the protein of unknown function. Interesting patterns in both the DNA and amino acid sequences lead to the belief that the protein was transmembrane with highly hydrophobic regions within the membrane joined by hydrophillic regions which would be the turns either side of the membrane. Using protein databases, and making inferrences from homologies with other proteins, it was confirmed that this was probably the case. During the project, the opportunity arose to write a piece of software to find repeated sequences and palindromes within the sequences of both the DNA and the amino acids. As a first attempt at using Java to make scientific software, this turned out to be reasonably successful and I look forward to further opportunities to use my programming skills in the future. The dissertation can be downloaded from here.

My Interests

One of my biggest interests is the use of and mastering of computers. I enjoy all aspects of computing; particularly programming. I have recently purchased an iMac (before they went aluminium unfortunately) and have enjoyed the flexibility OS X offers its users, and the sleek interface it runs. I have an exceptional understanding of all version of Windows, and of computer hardware, which I have put to good use in the past by assembling my own computers from components in an attempt to get the best performance for my money. I have also had experiences in Linux and would love to take up an opportunity where I can exploit my understanding of this operating system. My experience with Macintoshes is becoming quite in depth as illustrated by the fact that I officially support their use amongst the 2007 MSc students in Systems Biology. I no longer have any computers at home running Windows as the main operating system and I would confidently say that Macintosh has become my platform of choice for almost any computing task.

Until recently, I had become very good at quickly and accurately solving Sudoku puzzles. Despite their apparently complex nature, by applying very simple rules to the grid it is possible to solve them without using any guessing at all. Using these rules, it is possible to solve almost any Sudoku puzzle in under 30 minutes, with most taking no longer than 10 to 15 minutes.

I had taken to playing online Texas Hold-em Poker since I started at Warwick. This is partly due to my interest in the game as a statistical challenge, but also because in my opinion it is one of the only card games you can play without leaving your path to becoming a champion down to chance alone. There is always an element of chance in a game, and it will occasionally catch you out, but as I have read before, the game is not just about being a good player, it is also about attacking your opponent with heavy bets when he is making mistakes. So it is also a psychological game. All this makes for an intriguing game that never tires. I used to play for small amounts of money, although I have become out of practice more recently due to the large amount of time it takes which I just cannot afford any longer.

I enjoy movies and TV series such as Family Guy and The IT Crowd alongside Peep Show and some oldies like Red Dwarf. Generally anything with good humour goes down well with me. I enjoy zombie movies, horrors, comedies and action movies. However I am not very picky and most movies show at least some appeal to me. Recent favourites have been I Am Legend and The Simpson's Movie. I am particularly looking forward to seeing National Treasure: Book of Secrets soon.

Miniprojects

As a part of my MSc year at Warwick, it is compulsory to complete two miniprojects. The first of these was a theory project involved in studying microarray data using statistical techniques in order to observe timecourse changes in gene expression in senescing leaves of Arabidopsis thaliana. The outcome of this was that I was able to develop further a piece of software written in the R project called MAANOVA. This is now able to handle much bigger datasets and has been given much more functionality than it originally had. For the details of the work I did here, please refer to the written submission which can be downloaded here.

Whilst doing the first miniproject, I attended the MOAC conference in the lake district. This resulted in the presentation of a poster about the project, which in turn won the competition for best poster at the conference. This can be downloaded here.

The second project was looking at the movement of vacuolar proteins within plant cell after their production in the endoplasmic reticulum. For this, a labelled protein was produced by genetic cloning in the lab. This protein is retained within the ER and fluoresces red when exposed to laser light of a specific frequency. This proteins allows me to use the confocal microscope to find the ER where the protein of interest is being produced. This protein of interest is tagged with a photo activatable form of green fluorescent protein. By activating the protein within the cell of interest using a UV light, the path of this protein can be observed over time by following the green movement within the cell. Use of the microscope confirmed that both proteins were working properly in terms of their fluorescence but the vacuolar protein was taking such a long time to move through the cell that the sample was tiring before the green had been seen to move. As the project was nearing an end with no useful results attempts were being made to view the movements in different and novel ways. These were partially successful and some results were obtained for the experiment; although with a little perseverance it should be possible to obtain clearer results using the construct produced.

Videos of the ER being activated and the result can be obtained from here:

Video 1 shows the ER in red and then the big green lozenge is the UV laser activating GFP. Once the laser is turned off, the GFP glows on its own. This can be seen to proliferate through the immediate channels of the ER, and as can be seen when the Z-position is changed, the green starts to proliferate through the cell.

Video 2 shows the entire cells ER glowing green. This happens when the activated GFP starts moving throughout the ER lumen. When the Z-position is changed, it can be seen that the GFP is in all parts of the ER and nuclear envelope now, only 3 minutes after activation.

The submission for this project was a poster and a journal style article. The article and poster are both available for download.

PhD Project

Having attained my MSc in Systems Biology, I have now moved onto my PhD which I am currently concluding in my final year. My project's title is "Modeling transcriptional networks in plant senescence" and is being supervised by Vicky Buchanan-Wollaston and David Wild. My overall aims are to find out which genes are interacting during plant senescence and to build interaction network maps of these genes. This is to be achieved by studying a highly replicated and robustly designed microarray experiment data set using computational tools. The first of these tools is MAANOVA which is currently in development by the Jackson Laboratory in Maine, USA. Whilst their software is comprehensive and has been chosen due to its ability to take the design of the experiment into account as well as handle mixed model fitting; it has been necessary to implement new features as a part of my PhD in order to better analyse our data. This work combines very nicely with their most recent changes to the software which appear to focus more on the model fitting methods. Once this stage is complete; technical replicates within our data will be collapsed, leaving only biological replicates which can be used in a piece of software written jointly by David Wild amongst others. This software operates within MATLAB and uses Bayesian network inference and Monte-Carlo Markov Chains to identify interactions between genes. This method does not make assumptions that interactions between genes are direct and will show hidden states within the model for genes which may not be present on the microarrays. Interactions from this software can then be mapped using Cytoscape which is a tool designed for visualising the output from such analyses.

Once a network has been produced, it will be possible to identify the nodes and see what effect knock out or over expression of these genes have on the network. Confirmation or rejection of these interactions can then be used to form a set of priors for the model which should produce better output on a second attempt. By repeating this process, interaction network maps will become refined and hopefully the goal will become achievable.

A selection of graphical outputs currently being produced by MAANOVA after development by myself with the advice of Andrew Mead can be found here.

Future Aspirations

Once I have my doctorate in Systems Biology, I intend to begin my career as a computer programmer for scientific software. I believe that the experience given to me by my research in Systems Biology has prepared me for this, and my personal interest in programming has given me the understanding I need to apply my newly found skills in this area. Systems Biology has proven to be a great combination for my experience and skills, and I look forward to making good use of it for the better of science in the future.

Photo of Stuart McHattie