Monday, 27 October 2014

First UTC Scientific Conference Commentary

You will all now be putting your feet up as half term begins, but I thought I would give you a little help in preparing your abstracts and summaries of your favourite seminar from the Malaria Meeting held at the University of Liverpool, last Wednesday in the Muspratt Lecture Theatre (appropriately chosen after one of the founding fathers of Chemistry at the University). 

Just to remind you all (and those who missed it) the running order was as follows:

1.35pm Professor David Hornby, Liverpool Life Sciences UTC
Opening Remarks

1.40pm Dr Alexandre Lawrenson, The Kingsway Academy
Virtual Screening to Identify Novel Antimalarial Chemotypes

2.00pm Emeritus Professor Michael Clarkson, University of Liverpool
Local Mosquitos – My Hobby

2.25pm Professor Paul O’Neill, University of Liverpool
Antimalarial Drug Discovery and Development in Academia

2.45pm Break

2.55pm Rachel Winrow, Liverpool Life Sciences UTC
My experience of Malaria

3.00pm Professor Richard Pleass, Liverpool School of Tropical Medicine
HexaGard: a biomimetic replacement for IVIg therapy

3.20pm The Memusi Foundation Team, Liverpool Life Sciences UTC

3.30pm Dr Mark Paine, Liverpool School of Tropical Medicine
Malaria: Of Men and Mosquitos

3.50pm Gap Medics

4.10pm Alison McGovern, MP
An Economic and Political Perspective on Malaria in Africa

4.30pm Professor Neil Hall, University of Liverpool
Genetics of the Malaria Parasite

4.50pm Professor David Hornby, Liverpool Life Sciences UTC
Closing Remarks

First of all,as an audience (Y12s and 13s) you were exemplary: engaged and, despite the intensity of the session, and the level of many of the talks, you were all an audience to die for. At least that's what all of the visiting speakers asked me to pass on. So incredibly well done! I found your questions to be searching and challenging and your confidence was at a level I rarely see amongst graduates!

So let me give my own synopsis of the talks. I am going to concentrate on the visitors' talks and say something separately about the UTC student talks in a separate Blog. The theme was Malaria, as you all know, but the content varied from Alison McGovern's consideration of our social responsibility as a developed nation in supporting the reduction in deaths from Malaria. Alison's style was more interactive than all of the other speakers and I would ask you to consider looking into the Millennium Goals that she discussed. You can find more information here. Your engagement was excellent, but mostly I hope she stimulated your interest in the important economic, societal and ethical issues she raised. As responsible citizens, when you are able to vote for the first time, you should really follow Alison's advice and inform yourself about the challenges and responsibilities that she discussed in such a lively and passionate manner.

The first seminar of the day was delivered with great clarity by Alex Lawrenson, formerly a PhD student in Paul O'Neill's chemistry lab at the University of Liverpool who has moved through industry before re-surfacing at the Kingsway Academy. Alex explained the frustrations for all pharmaceutical companies in tackling the 15 year barrier to "getting drugs on the market". Clearly, we don't want drugs to be made available before they are thoroughly tested, but 15 years is a long time. Just look at the debate surrounding Ebola treatment at the moment. The suggestion that Alex discussed, with examples drawn from his own research, was to utilise algorithms that search chemical and structural features of "compound libraries" in order to reduce the time taken to identify promising therapeutic molecules. This "in silico" approach utilises software that matches ideas from the medicinal chemist (which include not only the potential steric fit of a compound to its target [often a protein, and in Alex's case a cytochrome], but also its potential toxicity, stability, solubility etc.) in order to limit (or filter) the number of compounds to be screened. It is clear that these approaches are beginning to make a difference and I am looking forward to chatting to Alex further when he visits us at the UTC.

Paul O'Neill followed Alex later in the day, giving us a tour de force of Malaria drug discovery. The most interesting aspect from my perspective was the way in which Paul's group have taken Natural Products, in this case quinine and artemisinin (left), two historic treatments for Malaria, and addressed the challenge of not only improving upon them in an empirical manner (Science speak for systematic trial and error!), but also by using the insight gained from the target for these compounds: our old friend Haemoglobin, the Molecule of the Month in May. Since we have been using conjugated dyes to simplify our chromatography experiments over the last month, you will be familiar with me describing how molecules that are made up of "aromatic" rings are able to absorb visible light as a consequence of the reorganisation of electrons. Well, Paul suggested that the porphyrin ring (the key element of Haem, often written heme) can make highly favourable interactions with the compounds he has been designing and synthesising, inspired by the aforementioned natural products. In fact I went to PubMed to find the affinity constants and was surprised to find work dating back to the early 1980s on quinine interactions with porphyrin (eg Moreau et al (1985)). I'd love to read your thoughts on Paul's talk, since I know some of you found Alex and Paul's talks the most interesting. You should think about the fact, as Paul discussed, that female mosquitoes feed on blood and the accumulation of Haem that results is the drug target. This makes for an interesting story in itself, regarding Malaria and drug resistance mechanisms.

The Wirral's own Lake District
Before I cover the two talks from the Liverpool School of Tropical Medicine (LSTM), I just wanted to mention the seminar that proved to be popular with everyone (in fact, out of 50 students I asked, he was first choice as favourite by 48!). Michael Clarkson's talk proved a delight. He discussed his retirement "hobby" (Michael is Emeritus Professor in Veterinary Science at Liverpool: the title emeritus is conferred upon retired professorial staff who have given distinguished service at their institution, and often remain active in their field): monitoring mosquitoes on the Wirral. I thoroughly enjoyed Michael's delivery and the elegant way he developed his scientific thinking, while keeping us amused at the same time. It was an important addition as well, since he raised the important issue of diversity among insects: not all mosquitoes carry malaria and their life cycle preferences differ in many subtle ways, illustrating the challenges of managing insect borne diseases. This aspect could be something you might want to think about if you choose Michael's talk for your essay. I was also interested in why so many students found Michael so engaging. It wasn't difficult: his relaxed style and his natural enthusiasm combined with his perfect judgement in his use of language to develop his story, all made his presentation, the people's favourite by far.

The two talks from the LSTM illustrated the quite different approaches that form part of the School's strategy for supporting the eradication of Malaria. Richard Pleass described how his lab are manipulating the scaffolds of antibodies in order to understand the fundamental processes in immunity that lead to antigen elimination. As you will recall from my Molecule of the Month in January 2013, the structure of antibodies is broadly a Y shape. Richard described how his team are hijacking and remodelling, the stem of the antibody (called the Fc region) in order to steer the interaction with different classes of receptors. Richard is working with the Biotech sector in order to improve existing treatments for auto-mimmune disease, and these approaches are hopefully set to inform our approach to vaccine design. Mark Paine's group by contrast, bring together the enzymes used by humans to deal with toxic compounds that enter our blood stream, which in insects form part of a suite of defensive mechanisms for combating insecticides. As Mark explained, at the Biochemical level, we know how to kill mosquitoes, but we also know that unregulated (or excessive) exposure of insects to insecticides leads ultimately to "resistance" through mechanisms identical to similar bad practise in the management of antibiotics. Mark was clear that elimination of mosquitoes was his solution, and he explained how the use of bed nets (partly supply, education and politics!) and spraying regimes could be improved by the introduction of simple quality control and quality assurance assays. The importance of pragmatism in combating Malaria was evident in the way Mark combined Science, Education and the logistics and realities of life in those countries where Malaria prevails. It might be interesting for someone to compare and contrast Mark's presentation with Alison's above. 

Finally, Neil Hall presented a riveting account of the road to the Plasmodium genome. Neil moved from the Wellcome Trust Sanger Institute several years ago and heads up the Centre for Genomic Research at the University of Liverpool. As you might expect, such projects involve many people (although Neil's name is easy to spot in the two landmark papers in Nature in 2002!) and the clear advances in technology that have taken place (and continue to do so) are making genome sequencing faster day by day. Neil explained not only the methodology, but the impetus (from a historical context) for addressing Malaria through genomics, specifically discussing the regions of the Plasmodium chromosomes that make the organism such a surface "chameleon". In addition, he explained how a comprehensive knowledge of the entire genome, could address questions that were inconceivable before genomics. The integration of metabolic pathways and the analysis of the evolutionary mechanisms that have led to the peculiar organelles found in Plasmodium whose origins may lie more towards chloroplasts. These ideas would not have been possible without genomics. It is also timely to consider genomics, a Science that is part experimental and increasingly computational. When you return after half term, we shall begin our Bioinformatics project and using search tools provided by the National Center for Biotechnology Information (NCBI) in the USA, we shall be looking at some of the aspects Neil discussed in his excellent closing seminar.

Finally, a reminder: I am after a Scientific Abstract and a separate 1 page description of your chosen seminar for Monday the 3rd November, in the meantime have a good break (in between revision!). 

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