Friday, 20 February 2015

The importance of teaching seminar etiquette to students, as well as how to present them

I went to my first academic seminar in 1980, since then I have been to one a week on average, which means I have sat through over 15 000 seminars! In fact I haven't included scientific meetings, so I reckon 20 000. It seems a high number, but I reckon many of my colleagues are veterans of many more seminars. Some have been more memorable than others, but I have no doubt that seminars and presentations have shaped my views on Science in a profound way. Hearing Fred Sanger (top left) explain the principles of DNA sequencing of the lambda genome in the early '80s, was a privilege, if not the most inspirational of talks. Being enthralled by Sydney Brenner with his two overhead presentation of the wider implications of puffer fish genomics in a filled lecture theatre where you could hear a pin drop. These are memories that will (hopefully) stay with me. Then there were the seminars that irritated, frustrated, infuriated me, or just simply sent me drifting into a daydream. The truth is presentations and their style and content combined with the personality in front of you is not always perfect. However, I have witnessed Kim Nasmyth stand up at a meeting in Oxford (I think) in the early 1980s and deliver an impromptu chalk and talk presentation on the molecular biology of mating type switching in yeast, "about the time the slide projector broke" (to steal from Bob Dylan). It was stunning, and at the time, I was deep into the steady state kinetics of enzymes! (It's true!) This also make a point that some of my most memorable seminar experiences  have been on topics I would not have thought (in a million years) would be of any interest! In fact I have a rule of thumb for seminar attendance that says: "Dull title:must go"!

So seminars have stimulated, irritated, informed and entertained me over many years. I really can't get enough of seminars. I have already written about the value of seminars in an earlier Blog, but here I want to discuss the importance of the audience, the listener and the chairperson or facilitator. Just consider a presentation from a visiting speaker to a mixed audience. Let's say the topic is "Behaviour and Patterning in East Asian Lepidoptera" (just in case, butterflies and moths). The audience comprises students, academics, interested enthusiast and the age range is 14 to 84. The speaker, Professor Linnaeus has travelled by car from a  University seventy miles away, and the seminar is scheduled for 4.30pm. It's November and it's cold and wet! The audience begins drifting in ten minutes early and by 4.35, the chairperson introduces the speaker, a few words of background and a general welcome. Three more people drift in and the speaker overcomes the challenges of lap-top and projector incompatibility and dims the lights to maximise the impact of his slideshow. The pressure is now on the speaker to deliver an engaging presentation, legible slides, attractive images, a logical flow, evidence-based information and sometimes a little speculation to stimulate discussion. The closing minutes are devoted to acknowledgements: the support of colleagues and funding bodies and, where appropriate, a mention of any commercial interests.

Now it is the turn of the audience to play their role in the seminar. Some are there to listen and expand their awareness of a topic they may be largely unfamiliar with: such participants may often ask for clarification, which in turn may help the understanding of others. Some will be experts, looking for insight that they may have missed, or they may be more predatory; challenging the speaker's confidence in a controversial view or data that may have alternative interpretations. The widely held view is that scientific seminars should promote exchange of ideas and that personal rivalries or grudges have no place in the lecture theatre. Of course, we do not live in an ideal world, and the best laid plans can go astray! However, it is the responsibility of the Chair to manage the transition from presentation to discussion and on to closure, or to welcome the next speaker. An experienced session chair should stimulate discussion, if the speaker has failed, or the audience are silent. Seminar etiquette is such that an audience should show engagement with the speaker and the presentation by asking one or two questions. However, it is also important in situations where several speakers are presenting, that the chair keeps the speakers and the audience in check to ensure speakers have approximately equal time to present. 

What is not acceptable is audience hectoring, where one or more individuals take against the speaker and repeatedly challenge a point, or in some cases take the discussion away from the main theme, in order to "steal the show". Here, whilst some speakers are able to "handle" such heckling, sometimes the chair has to intervene, but if this fails, the audience must make it clear that such outbursts are inappropriate and that (especially personal) disagreements should be taken "offline".

In conclusion, seminars from visiting speakers or at scientific symposia are a two way event and both speaker, audience (and chair) need to understand the rules of engagement! I feel that audiences should, on the one hand, be less passive in scientific seminars, but on the other, they should always be courteous, and should choose the most appropriate way of challenging a speaker. This will sometimes be during a talk, after a talk or sometimes in private. However, I do get irritated when audience members walk off down a corridor mumbling to colleagues that "Who on earth funded that project", or the evidence for that particular conclusion doesn't take into account any of my last two papers! So maybe we need to teach students how to participate in seminars, not just how to present one!

Saturday, 7 February 2015

First Nobel Laureate to visit the UTC! Sir Tim Hunt Part 1 (Intro)

This week we are delighted to be hosting a visit from Sir Tim Hunt at the UTC. Tim was awarded the Nobel Prize in 2001, exactly 100 years after the first such prize was awarded. Tim shared the award with fellow British scientist Sir Paul Nurse and American Biologist Lee Hartwell. They all worked independently, using quite different approaches to unravel the key components of the eukaryotic cell cycle. The work that Tim carried out involves identifying the key cell cycle protein cyclin using sea urchins as an experimental model. Tim ( the Sir gets in the way sometimes!) was born on the Wirral, his father was an academic in Liverpool, but soon after relocated to Oxford where he eventually attended the well known Dragon School! Tim's early career was based at Cambridge, and saw him following his interest in protein synthesis. 

He visited a number of groups in New York during this time, and importantly the Marine Biology Labs at Woods Hole. It was here that the cyclin story began. This is a story paved with a series of elegant experiments and I shall take you through it in the second part.

Sunday, 1 February 2015

Molecule of the Month February 2015 Human Immunodeficiency Virus

This month I have taken the liberty of discussing a collection of related proteins, that together make up the virus at the heart of Acquired Immunodeficiency Syndrome (AIDS): the Human Immunodeficiency Virus (HIV). For the purposes of the Blog, I will consider HIV as a multi-protein complex in which an outer shell of proteins, protects an inner core that contains the RNA genome and accessory molecules. A little Biology first, HIV is a retrovirus, that is, its genome is RNA based and therefore it requires a conversion step in which the enzyme Reverse Transcriptase copies the viral genome into DNA, as a prelude to its insertion into the (human) host genome. 

A circular structure with purple structures coming out of it and a number of objects inside the circle representing different aspects of the virusThe virus genome comprises 3 primary genes: Gag, Pol and Env. These 3 genes each encode a poly protein which is then processed to form the HIV proteome. The Gag proteins (for group specific antigen) are proteins that organise the interior of the virion. The Pol polyprotein encodes enzymes for replication of the genome, including reverse transcriptase, that catalyses DNA synthesis from RNA, and an Integrase enzyme that inserts the DNA into the host genome. The other key protein that is co translated with RT, is the HIV protease, itself required for processing of the polyproteins. Finally, the Env polyprotein comprises the envelope(or surface) proteins, gp120 and gp41 (gp means glycoprotein, a protein that is normally modified by the addition of carbohydrate after synthesis on the ribosome). The genome also encodes essential regulatory elements which are expressed as RNA species: these are called Tat and Rev. A good introduction on the complete set of HIV elements can be found at this link. I shall mainly focus here on some features of the proteins that have been of interest in both vaccine development and drug strategies.

Zidovudine.svgReverse Transcriptase received a mention in an earlier Molecule of the Month: RNA Polymerase. This enzyme, like all nucleic acid polymerases takes the building blocks of nucleic acids, ATP, CTP etc for RNA or dATP, dCTP etc. for DNA and inserts them one by one in a single direction, as directed by the complementary sequence of bases on the template DNA (or RNA). RT carries out the opposite reaction to a typical RNA polymerase: the enzyme synthesises DNA from an RNA template. The single strand is then copied into a double stranded form and the resultant duplex is incorporated (or integrated) into the host genome by an enzyme called an Integrase. These two reactions are distinctive. Whilst there are many similarities to host nucleic acid polymerases, there are also significant mechanistic differences. This presents an opportunity for drug development. (Students, think about this concept: it is an important aspect in the design of new drugs such as antibiotics and anticancer agents). The first drug released to combat AIDS was called azidothymidine or AZT for short (its commercial name was first zidovudine and finally Retrovir; it is pictured top right). It is an inhibitor of RT, with around 100-fold preference for RT over our own DNA Polymerases. First the cell converts AZT into the triphosphate and then the RT is blocked competitively at the active site. High doses have significant side effects which are directed at the mitochondrial DNA replication machinery (causing muscle fatigue). However, it is currently used in combination with other drugs as willbe discussed below. Nevertheless, the mechanism of action of compounds such as AZT, reveals how drugs must be developed not only in respect of the target, but e so called "off target" sites, that are the source of some side effects. If you are interested, you can read about the "rise and fall of AZT", the first anti AIDS drug here

The second classical target for HIV therapy is the HIV protease (shown left), which is required for the maturation of the polyproteins expressed from the RNA genome of HIV. This enzyme uses a pair of catalytic aspartate residues, one form each chain of this dimeric enzyme, to process the HIV polyproteins. (It is sometimes called an aspartic protease). By synthesising peptide based analogues of the substrate, constrained to mimic the "transition state" of the reaction, it has become possible to treat AIDS through administration of compounds such as Ritonavir and Lopinavir. However, it is more usual to combine RT and Protease inhibitors in a cocktail to produce what are referred to as combination therapies, discussed in more detail here. This reduces the emergence of resistance, caused in part by the high mutation rates of the HIV viral genome, together with the heterogeneity of virus strains that seem to be associated with some infections. The development of anti AIDS drugs, in particular the anti-protease inhibitors, is often cited as one of the most significant successes of rational drug design, based on crystallography and modelling.

The final structure I wish to mention is the gp120 molecule, which is the target of a number of immunotherapy strategies. Again, mutation rates present a challenge for ani vaccine programme, but AIDS vaccines are particularly difficult to develop owing to the mutability of the viral genome. Professor Dennis Burton's group at Scripps in La Jolla, Callifornia, are in the vanguard of approaches to neutralise HIV. The structure on the right, from the Wilson-Burton groups at Scripps, provides detailed structural interaction information, which is currently reducing the odds of finding a potent vaccine. Indeed in last year's Science the team along with International collaborators made significant advances towards this goal. One of the most important issues that AIDS research has told us is that the recognition between proteins in the design of vaccines, must also consider the significant role played by carbohydrates and the masking of amino acids by sugars, which presents another major challenge to vaccine discovery. However, as the structural information becomes richer, success will surely come.

Finally, the challenges to human health brought by retroiviruses such as HIV and Ebola, demonstrates how Science thrives in adversity and I am sure that despite the current Health challenges, we will be in a better position to meet new diseases that are undoubtedly lurking around the corner!