Prior to starting the Systems Biology MSc, I thought that I would be pretty well prepared. I'd just finished an undergraduate masters degree containing some very challenging and enjoyable units, so expected more of the same. Whilst this is what I got, there is a significant shift from undergraduate to postgraduate learning style. The five week courses lead to rich information pools (which I preferred to the slow accummulation used in my first degree, though the pace was such that you have to keep right on the ball.

The style of the course - simultaneously learning statistical inference and microscopies, or bioinformatics and biological techniques, though the results were rewarding and the team spirit within the cohort was very strong due to the tutor/tutee roles that would swap over at work and the social elements that we tried to weave in on the evenings!

Introduction to Biology

For me, highlights from the taught half of the MSc included the group poster presentation (see poster to the right) as part of the biology introduction course (CH920). Together with Tahani Bawazeer, Gregory Rees, Sophie Royall (all IAMBEC) and Mike Downey (MOAC), the poster was produced to present the following paper by Yan et al.:

• Structure of the CED-4–CED-9 complex provides insights into programmed cell death in Caenorhabditis elegans. Nature, 437, 831-837, 2005.
  

Further to this, I have subsequently produced posters for each of the mini-projects in the MSc, copies of which can be found in the posters section in the navigation bar on the left.

Biological Systems

Another early piece of work in the MSc course was that of the joint presentation (in pairs) of a recent paper relating to a topic in systems biology, so as to aid the understanding of what work is currently being done with biological systems (BS914). For this piece of work, Richard Hickman and myself presented a paper by Wolf-Yadlin et al., regarding the effect upon cancer of over-expression of the epidermal growth receptor - HER2. The paper uses self-organising maps in order to cluster gene responses to different conditions over a 30 hour time course.

• 'Effects of HER2 overexpression on cell signaling networks governing proliferation and migration'. Molecular Systems Biology, 2, Article 54, 2006.
  

Advanced Bioinformatics

This mathematical unit (BS915) is targetted at those students with a theoretical background. As such, the material contained within the unit is more advanced, commencing with Bayesian theory and developing further into BLAST, dynamic programming algorithms and Hidden Markov Models (HMMs). Further work presented within the course included the use of Matlab as a mathematical programming tool, and the formation of sequence logos (example created at http://weblogo.berkeley.edu/logo.cgi) when looking at multiple sequence alignments.

Numerical Methods

In spite of my track record as a mathematician, this unit, taken by all students in both the Systems Biology and MOAC doctoral training centres was far from simple or a matter of revision! My undergraduate maths degree focussed on the purest theories that give precise solutions. In (CH925), we were introduced to many techniques that are used in order to rapidly determine an approximate solution to a problem. These range from simple methods, such as finding an intersection with a line, or determining a polynomial that passes through all of a given set of points, to making first order computational approximations to the diffusion equation within the Maple environment.

Technologies in Systems Biology

The technologies unit (BS918) was one which started to really bring some of the biological concepts that had previously been introduced, into the real world, showing how data is obtained and examined. Ranging from the collection of high throughput-data, such as that gleaned from microarrays, to image analysis that can be utilised in the study of flourescence of GFP tagged proteins, this unit gave a solid background as to how things are done in a Systems Biology context. A real highligt of this course was the microarray experiment which we both ran and analysed regarding leaf senescence in Arabidopsis thaliana, as per the work of Vicky Buchanan-Wollaston, at Warwick HRI.

The four images (from left to right) show (i) a time-course analysis of leaf senescence in the genes of Arabidopsis thaliana, from GeneSpring; (ii) a cluster of genes with decreased expression, from Splinecluster; (iii) a Splinecluster dendogram, showing the clustering of the genes expression profiles; and (iv) the Mapman response for the most differentially expressed genes at day 11.

Modelling and Statistics in Systems Biology

Almost undoubtedly the most difficult material for me personally in the Masters syllabus, was this statistical unit (BS917), which was again for those students in the theoretical stream. This course takes a rapid approach, considering tools such as Markov chain Monte Carlo (MCMC), the Gibbs Sampler and the Metropolis Hastings Algorithm, as means for determining the probability distributions of a given problem. In the context of the course, the set-up usually involves gene networks, including positive/negative feedback loops and co-activation. Further consideration is also made of hidden variables, as well as the incorporation of different types of data into a mathematical frame-work, and te role of stochasticity when considering biological recordings.

Data Acquisition II: Microscopies

This unit (CH922) is taken by both the MOAC and Systems Biology students and features further techniques that may be useful when attempting to image biological samples. These range from standard light microscopy to fluorescent markers such as green fluorescent protein (GFP), which allow for imaging via the shining of specific wavelengths of light. The image to the right shows GFP stained pyramidal cells and GABAergic interneurons are stained red. There are also more chemically operated processes, such as scanning electrochemical microscopy and scanning ionic conductance microscopy. Finally, two touch based methods are also introduced, the first being atomic force microscopy, where the contours of the sample are physically touched to provide an image. The other touch based method is in the form of electron microscopy, in which high energy electron beams are targetted at samples, and the manners of deflection used to determine the precise shape of the sample of interest.

• Image taken from Lee et al. 'Dynamic Remodeling of Dendritic Arbors in GABAergic Interneurons of Adult Visual Cortex', PLoS Biology, 4(2): e29, 2006.

Networks and Pathways

The final MSc taught unit (CH927), brought together several aspects of what had been learnt in the previous units. Here, the notion of interacting regulatory modules, or ReMos (far upstream non-coding regions of the gene which have a significant impact upon the transcription level of the gene in question. The work involved division of the year-group into teams, each with slightly different aims, though aiming to understand and explain the synergies present under different combinations of ReMos for a certain gene being investigated in the Koentges laboratory. Through the investigation of various types of transcription factors, utilising such information as binding locations, binding synergies, bridge building, DNA building etc, each team produced a theory for the data provided to us, presenting the work in an extended presentation (20mins for each team member) and utilising the programming skills of various team members who provided a visualisation tool for the research being carried out.

Mini-Projects

Although neither of my mini-projects were successful in terms of the quality of results yeilded, I believe that they were highly beneficial as part of the training provided by the DTC as part of the MSc year. Without them, I would not feel as comfortable as i now do in my PhD, whether in the lab, or when scouring literature of either biological or computational type. More information on the mini-projects that I chose, in addition to full-sized PDF copies of the posters summising the methods and results, can be found in the posters tab in the left hand toolbar.