 Can I start by just asking you to introduce yourself? Yeah, I'm Andy Waters. I'm a professor of developmental and molecular parasitology at the University of Glasgow, working on malaria parasites, in particular a rodent model of malaria parasites, Plasmodium burgii, and I'm also director of the Welcome Centre for Molecular Parasitology, which is based obviously here in Glasgow as well. And what will you be talking about at Thames? I'll be talking about the work that we do on sexual commitment in malaria parasites. The transmission of the malaria parasite from the mammalian host to the mosquito vector, which is the agent of transmission, is clearly a critical process in the parasite life cycle and is essential for the spread of the disease. And it is only the sexually committed forms which are capable of affecting that transmission. So clearly one of the key questions over the years, since the discovery of the full life cycle, has been how does the malaria parasite generate these sexual forms? It's a developmental decision that the parasite must make whilst it's in the bloodstream of the infected mammalian host. Typically what happens is that 99% of the parasites that are in the bloodstream are asexual and they are going to invade a red blood cell, grow, divide, lyza red blood cell, reinvade the next generation of blood cells and amplify their infection that way. A small proportion of those parasites, the one to five percent or so, will actually undertake a separate and distinct developmental pathway which is then sexual commitment. That happens within the context of the red blood cell and it results in a stable form of the parasite and it's dimorphic so there's a male and a female form and what we're trying to understand then is how the parasite makes that developmental decision. And over the years our work and that of many others has honed in on a series of molecules and a particular one transcription factor which is an essential player in the commitment process. So without that particular transcription factor which is called AP2G it's a member of a large transcription factor family. Then in the absence of that protein which we can achieve through genetic manipulation of the parasites which is something else that my laboratory is very keen in developing. Then the absence of that protein means that you don't get commitment to sexual development you don't get the formation of these fully developed male and female sexual forms which the parasitological term for those of gametocytes then in the absence of that protein you don't get those forms and therefore you block transmission. Clearly this offers us ways in which we might then attack ultimately to prevent the development of those forms as one strategy for the fight against malaria and if we were to be successful in blocking that protein or processes surrounding the expression of that protein then we would be able to stop the transmission of malaria and clearly that would be a great advance. So having discovered this protein what we now need to know is how is that protein regulated? We know now that it's regulated at the level of epigenetics and so the region of the gene that encodes that transcription factor is in what we call facultative heterochromatin and that means it can switch between eukromatin and heterochromatin and that's regulated by modifications on the histones which surround that gene and lie immediately upstream of that gene and what they do is switch between switch the marks on the histones which control accessibility to that gene so they can either be in a repressed state which they are 99% of the time or on occasion they're open. So having got we've now travelled from the production of the identification of this transcription factor which is necessary to the regulation of the expression of this transcription factor and my work now and what I will describe apart from giving some obviously some background during my talk what I intend to describe is the next level of regulation we have discovered which harks back to an area of research that my group used to work on so in a sense we've come full circle because it lies at the level of translational regulation and so we're putting together the pieces of this jigsaw of commitment to sexual development by a malaria parasite bit by bit there are still lots of gaps but now what we've been able to show is that there is a stable ribonuclear protein particle that's maintained in the parasite cytoplasm and that the messages which are associated with that the message RNAs which are associated with that particular particle when we dissect their roles individually we can show that they are responsible for the rate of growth of the parasite in general and the ability to make either males or females and that's all in the same particle at least as far as we're able to resolve it at the moment we may single cell technologies as they're coming online and being adapted to malaria research will enable us to answer this in greater detail but at the moment what we've been able to show is that this translational repression complex exists we know the critical protein we know that it itself is post-translational regulated and that the post-translational modifications control the ability of this ribonuclear protein to deliver RNA effectively to a ribosome for translation and I think we've so what we've opened up is a new layer of regulation of commitment to gametocytogenesis what we also hope to be able to understand is how this works at the population level so if on dissection what we show and have shown so far is that the those three effects of perturbing that particular ribonuclear protein particle i.e. growth commitment to males or commitment or production of male gametocytogenesis, production of female gametocytogenesis then is that operating at a population level or is it actually operating at a single cell level so does every cell make that decision or is it predetermined in some way that we as yet don't yet understand and so what we need to be able to understand now is the complexity of that ribonuclear protein particle in each and every individual malaria parasite cell in the bloodstream and with that knowledge we'll be able to then address whether or not the parasite is making that it's already made that decision and that translational complex is simply again and if one part of the pathway towards production of gametocytogenesis or is that actually if you like the central hub through which the decision is actually affected to either continue going around in the cycle of asexual blood stage growth multiplication division and or the branch off to produce either the male or the female form so I hope actually to have substantial data to address that last question by the time we come to meet in person there are other levels of regulation as well and that the parasite is sensitive to its environment so colleagues here in Glasgow have actually started to unpick some of the proxies that the parasite will sense that are present in the bloodstream of the infected individual that in some way give an indication of the health status of that individual and so it's nutritional the availability of specific and key nutritional components for the parasite growth. The parasite senses the abundance of a particular serum component when that component is abundant it's called lysophosphatid alkylene when it's abundant then it's a nutrient that the parasite requires for efficient growth and so it continues to grow it continues to multiply it maintains the asexual cycle in the paucity of that component the parasite senses this and then switches to the production of the gametocytes so that does two things first of all is the parasite senses that the host is not as well nourished as it is ideal for the parasite growth equally if it's not that's a signal to the parasite that further commitment to transmission and transmission is an investment the parasite makes because it doesn't have to make gametocytes it only makes gametocytes when it's optimal or in cases of times of emergency such as malnourished hosts so then it can switch its resources to making more gametocytes in the hope that the evolutionary strategy is then transmission is the preferred option so flooding the system or with gametocytes or certainly making them far more abundant than they would normally be is a way to gain the outcome towards transmission and persistence of that particular parasite line which then of course leads to an evolutionary strategy it obviously has an enormous human impact and I think that's why most people start studying it is because they understand the health problem that it causes but you get drawn in by the biology so idealistically I was there to try and cure malaria find a vaccine component and that's how for my first postdoc I entered malaria and didn't stray but being increasingly drawn into the complexities of the biology to understand its basic activities and the processes it uses to complete its life cycle and a lot of it is just biological fascination that keeps one going but equally at the back of your mind there is the knowledge that if you understand it well enough then you might be able to interrupt it and therefore go back to the original reason for studying that in first place. Is there anything in particular you're looking forward to with the conference? Well I mean obviously Glasgow makes it very convenient but I also think Glasgow is a great city and very much underappreciated by the world almost it was one of the world's great cities in its heyday and there are traces of that all over the city and it's retained a very warm welcoming environment and so I think that the delegates when they come will have a fantastic time the venue is very close by one of the gentrified areas of Glasgow which is vibrant at night lively during the day even more so at night and I think they'll have a great time so I'm looking forward to welcoming everybody there I was a member of FEBS in the past as a PhD student for a while attended some of their conferences so I know what the federations the quality of the meetings that they produce can be so I'm sure this is going to be an exciting meeting and there will be a lot of cutting edge science and in fact the person who invited me has a Penaardis who's I think one of the organisers and works a few floors below me some of the work that he's doing is utterly marvellous and transformative so if the programme reflects that type of quality then it's going to be a wonderful conference Is it just the science itself that you find rewarding? One of the joys of being a group leader is the scientists that you work with, the young scientists that you work with and so over the years I've been fortunate enough to have a lot of extremely talented people come and work with the goals that we have as a group to try and understand the malaria and a lot of them have gone on to quite successful careers and it's seeing these scientists emerge and develop and know that you've played some small part in that is actually a wonderful part of the process as well and it's still great to be able to have PhD students at the outset of their career even MSc students and undergraduates come in and see them not only become enthused by the subject but see that the people who are already members of your group are passionate about what they do and transfer that on so you can see this complete lineage of communication and continued recognition of the complexities of biology the mysteries it still holds why it's exciting and important to understand these things and to know then that this is a message that I think for some of these people is actually life changing because they do take it very much to heart and understand that there's a great requirement to generate this knowledge that's it.