 Okay, good afternoon everybody. So it's a pleasure to welcome you here and also to welcome Professor Lawrence Banks from ICGEB. Professor Lawrence Bank, he's Director General of the International Center for Genetic Engineering and Biotechnology, ICGEB. It's an international scientific research organization to promote sustainable development through advanced research and education with headquarters in Padrichyan, Uttar Yastai, and in many ways it's really a sister organization of ICTP, what ICTP does in Theoretical Physics they do in a different field. He was, he did his PhD at Leeds University and he has been one of the important members of ICGEB since 2000. He was the scientific coordinator at ICGEB since 2016 and then a group leader of the tumor virology laboratory since 1990, so he's been here almost more than 30 years. His current interest is in human papilloma viruses, HPVs, the causative agents of a number of human tumors and the most important of which is cervical cancer, which is a major cause of cancer related death in women worldwide and his laboratory has made many ground making contributions to our understanding of how HPV enters the cell and subsequently brings about the changes resulting in malignancy. So I requested him actually, I had the opportunity, they had invited me to give a colloquium on black holes and topics like that at ICGEB and since the biologists suffered through black holes without complaint, I thought that it would be a good idea, I mean it's actually a pity that we are, ICST has this very nice science system and we often go to other parts of the world and give colloquium talks there and we don't know what our neighbors and colleagues are doing. So I thought that it was a very good idea from ICGEB but I thought it would also be good for us to know what ICGEB is doing and in particular what Lawrence is doing. But I also requested him that to maybe say after his talk on his own research a little bit about ICGEB so that we come to know what they are doing and some of our sections like QLS, I think I see Matoyos here have potentially very interesting links and I think some of my colleagues are actually collaborating with like Yakopo Grilli and also going in the future perhaps in computing in many aspects there are data science, there are now some convergences that could be very interesting for ICTP and ICGEB to look into in the future. So I welcome Lawrence to give his talk and then we'll have light refreshments after the talk. Thank you. So good afternoon everyone, Atish thank you so much for welcoming me here and for the introduction. I feel like the little brother visiting the big brother here because obviously ICTP was really the founder of the international system here in Trieste and ICGEB was founded, one of the major reasons we were located here was because of what you guys had already started so it's a great pleasure to be here. As Atish said I think we don't really know enough about what's going on in Trieste, we go all over the world and have great networks but I think it would be nice if we could also try to work together a little bit more closely and I think you know the emergence of technologies in science now, the fact of multi-disciplinarities needed in many many different fields, I think the opportunities there for collaboration are really very good. So what I'm going to do today is to try and tell you a little bit about the work that my lab does, I'm going to try and keep it fairly non-technical and really just to focus on aspects related to this group of viruses, human papilloma viruses which I think I'm sure most of you have heard of, you'll have heard of the vaccine, these are still very very important human pathogens and cause a very large number of human tumors throughout the world particularly in developing countries which is obviously something that we all share in common, we all work with countries in transition, least developed countries, low middle income countries and so human papilloma viruses there is really a major problem and then what I thought I'd do at the end is to give you just a very quick summary of ICGB's current activities and in particular some of the programs that we've got running in our different countries which may be of interest to some of you. So first of all moving on to the, so human cancer, we all hear about it every day, it's one of the major causes of death and a very significant proportion of human malignancies are caused by infections and around 12% of the total cancer burden is actually caused by viruses so that's really very significant and one of the reasons it's significant is that viruses you can vaccinate against so for the very simple reason that you know 12% of human cancer is preventable by simple vaccination. These are the viruses that cause human cancers and we've known about these since the early 60s and as you can see as we go through this timeline it's been a long slow process of identifying different viruses that cause different human malignancies and there's really two major points I'd like to take from this slide. First of all the type of virus that causes cancer it's very diverse. You can't say it's this particular class of viruses that are going to be cancer-causing and everything else will just go in in fact to sell, cause disease and that's the end of it. No it's quite a diverse group and it all started with Epstein-Barr virus back in the early 60s when it was found to be associated with Burkitt's lymphoma in Africa and nasal pharyngeal carcinoma in Asia. Since then we know it's actually responsible for quite a lot of other lymphroproliferative disorders and is really a major human carcinogen. The hepatitis viruses hepatitis B and hepatitis C both very different viruses, one's a DNA virus, the other one's an RNA virus so even though they're called hepatitis they're very very different viruses they obviously infect the liver and they both cause liver cancer. HTLV again this is an RNA virus, causes leukemia again this is predominantly within populations in Japan. Then we have human papilloma viruses which I'm obviously going to spend most of my time talking about but more recently you know another herpes virus Kaposi sarcoma virus which causes Kaposi sarcoma. That was a cancer that was known for many many years but it was with the HIV pandemic that this really came to prevalence because basically this cancer is really prevalent in individuals that are immunosuppressed and that's how that particular virus was identified. And then finally the last one that was discovered in 2008 is Merkel cell polyomavirus. It's a virus that in many ways is very similar to human papilloma viruses and this causes skin cancer mostly in older patients so people 70s 80s it's not a very common cancer but it's prevalent particularly in that age group. I said there were two major points I wanted to take from this slide. The other one is that all of these all of these viruses are what we would call persistent what does that mean? It means that when you're infected they stay with you most often for life. The majority of the viruses that are out there you think about influenza it comes in bang crash wallet two or three days you're either recovered or you're very seriously ill but it doesn't cause cancer and that is the case with the vast majority of viruses they go in they infect a cell they reproduce themselves eventually the immune system clears them you pass on the virus to other people but that's it that's the end of the story. With these group of viruses that once you're infected in the vast majority of cases they remain with you for life and that is one of the key points about viruses and cancer the viruses that cause cancer are those that stay with you. Hepatitis for instance is a chronic inflection somebody's infected with hepatitis B or C they have it for years. X-line barvirus you have it for your life you get infected with it and it goes into a latent phase and it stays with you forever. The same is also true with caposes with Merkel and we also believe with human papilloma viruses. So that is a key point so if someone comes to you and says I'm looking I have a cancer I don't know what the cause of that cancer is I think it might be a virus the first thing you would want to look at are viruses that have these sort of characteristics that ability to persist. So human papilloma viruses they account for about five percent of the cancer burden and I say cervical cancer is the most important and and that is by far and away the case they account for essentially a hundred percent of those cancers. You can find very very occasionally a cervical cancer which doesn't have HPV but it's extremely rare. It also causes a large number of other genital cancers probably around 70 percent and something that is really of great concern in in many parts of the world is it's also responsible for a growing number of head and neck cancers and in the U.S. for example head and neck cancer caused by these viruses has actually overtaken cervical cancer so it's really a really major problem and many of those cancers are really more prevalent in males than in females. So globally we're looking at around 600,000 new cancer cases each year that are caused by this group of viruses so it's a very major global health problem and what I've done here is I've list a series of numbers. Now you guys shouldn't be afraid of numbers so that's so I'm not worried about that but I don't want you to particularly remember these particular types but they're types of HPV and these different types of which there's 12 of them. They're all defined as cancer causing so in some landmark studies we did with WHO and IOC in Leone we basically worked to define that it was this small group of papilloma viruses which caused cervical cancer. Why was that important? There's around 300 different papilloma viruses have been described. Every single person in this room is infected with human papilloma virus. We all have it on our skin, we're shedding it, it's everywhere. The vast majority are not going to get cancer it's just this small group which are cancer causing so that's really quite an important point and that will bring me back to some aspects of the work that my lab is doing is to try and understand why do we have this group which caused cancer and then everything else which is floating around is a purely benign infection. Most of the time we don't even know we have it. I should add that there are a small number of papilloma virus types which infect the skin called cutaneous which have been linked to skin cancer in immunosuppressed patients and that's at sites where there's some exposure so there's exposure to sunlight has been an issue with those but that's still really quite a contentious point. So this is a map of ICGP's member countries like ICGP we work across the globe and as you can see we're prevalent mostly in the global south and overlaid on this map which is the countries in green as ICGP but overlaid are the prevalence of cervical cancer cases in different parts of the world and what you can see from this within southeast Asia cervical cancer is devastated and also within Africa these numbers grossly underestimate the frequency of cervical cancer in those countries. In parts of east Africa for instance cervical cancer is the single major cause of cancer related death and that includes if you that includes the whole population so if you consider that only 50% of that population can get cervical cancer it's still the major cause of cancer death so these are really devastating viruses in these these poor parts of the world and again this just shows you the the same information it's just stratifying different different cancers across the globe of whether mostly prevalent where they mostly cause cancer related death and as you can see here cervical cancer is really in the majority of cases the first rank cancer in what we would consider to be the developing world so it really is a major problem in those developing countries. I'll come back and say a little bit more about some of the issues that are faced there but what I'll do now is just say a little bit about the virus itself and why we think it causes cancer and please if I get too technical or there's questions you know wave please please jump up now and you know if it's not clear please ask for for clarification as I as I go through so this is this is the virus okay so it's made of double-stranded DNA it's circular and it just has a very small number of genes that it has within its genome so it's not a big virus it's about eight kilobases and you can divide it into three regions there's a region which is called early and so what that means is these are all proteins that are expressed when the virus first gets into a cell so these are proteins that are made very early on and they basically help the virus to replicate all viruses all they want to do is make more virus and that's what this set of proteins do then you need something that can make the virus how it's how it can transmit the DNA that the the particle this this thing here this is what it looks like what makes that particle what is these what what are the components well that's these these proteins here the lake proteins they make the capsid which is the core of the virus that's what you see down the microscope that's what everybody thinks of when you think about a virus it's these little round structures which carry the genetic material that causes the infection and then you have another region here which doesn't code for any protein but it just controls the expression of the genome it controls the production of those proteins and it has an origin for replicating the DNA so the virus can can be amplified now on this left hand side is is a section through your skin most viruses they infect a cell one cell and they take that cell over and they produce thousands and thousands of copies of themselves before that cell then normalizes or gets destroyed and releases more virus A coloma virus has an extraordinarily complex life cycle and that life cycle is dependent on how your skin forms so everybody the skin that you have here it feels quite thin but it's actually very complex structure the skin is an incredibly complex organ and the reason for that is obviously it needs to be an impermeable barrier and it's made up of many many cells that all form this structure okay and we all know that you know you cut yourself after a couple of days you have a bit of scar tissue it heals and then after a week or so no sign of it and that's due to this the nature of how this skin is made and what it consists of is this these cells here right at the bottom which are the only cells that can divide i.e a cell can replicate DNA divide itself and produce a daughter cell that daughter cell when it divides moves upwards from the bottom and so oops and so what you have is that all these cells that form up the layer of the skin are all originated from these cells at the bottom but they go through a process which is called differentiation it doesn't matter you don't have to worry about what that means it just means that there's no more ability for these cells to divide they're sort of static and they just make up the impermeable barrier of the skin now papillomavirus absolutely has to have this multiple layer of cells for it to be able to complete its lifecycle i just mentioned you can get lesions in the skin often very minor abrasions are sufficient to get infected with this virus and the virus gets access to these cells here in this basal compartment as these cells begin this upward movement to form the multiple layers of the of the skin the virus begins to express its different gene products and this process is really linked to this whole process of differentiation in the skin that does that make sense do people get that okay and so you will not get virus replication if you do not have this process of skin formation so that's really something that's really very unique about these viruses yeah two to three weeks two to three weeks so it's quite slow okay so just let me i'm figuring out the pointers so these here okay it's it says e4 e2 e1 it's three separate i'm sorry on the circle on the circle yeah so each of each one of these is a different protein yeah yeah so e6 is one protein then e7 is another e1 is another protein e2 is another one e4 uses a different reading frame within the same i see okay thank you got it one of the challenges that this virus has is it doesn't produce enzymes to replicate DNA okay it's utterly dependent on the host cell you'll probably realize that if we think about these cells here which is where the virus would replicate its genome i just said those cells are completely quiescent they're not capable of replicating anymore there's no machinery there to replicate DNA so this is a big problem for this virus and so what it does it has two gene products e6 and e7 which get expressed early and they essentially take these cells which are quiescent and they put them back into a proliferative state so the enzymes are present that can replicate the viral genome obviously one of the consequences there is that you're also potentially going to replicate cellular DNA so you immediately begin to see why this virus might be dangerous in the intrinsic part of the way in which it grows is to overcome the cells quiescent status or quiet just not doing anything and pushing it back into a state of proliferation and so you get here you then get viral genome amplification you then get here late gene products produced these l1 and l2 which then come together they take the viral DNA they package it into these capsids and you get once this process of differentiation is completed you get the release of the new infectious virus particles so that is that is the sort of model of how HPV normally replicates and the key point and why i've put it in red are these two proteins e6 and e7 because these are the two proteins that also cause cancer so i just had a question about the time this whole takes normally this part this life cycle would take place over two to three weeks and in any given infection with HPV probably will take three four months to maybe clear but in the vast majority of cases someone will get infected with papilloma virus and then the sign of productive infection i.e producing new virus will probably be cleared within about a two to three month period in some individuals that clearance doesn't take place and you have this persistent infection and i mentioned that in my first slide persistence is really critical the reasons for that persistence are still not known and obviously it's lack of immune clearance but why nobody knows but this is the single biggest risk factor for ultimate progression to the development of a cancer which can take place over 20 years some cases it can be much quicker the other feature of cancer development is that these two viral proteins that i just mentioned e6 and e7 which drive that proliferation here to produce more virus continue to drive proliferation here when we have a cancer is this part of the normal life cycle is this what the virus normally wants to do the answer is absolutely no this is what the virus is aiming to achieve producing more virus this is a dead end this will never produce virus it's a complete mistake we don't know why it happens we just know that when it does we often actually the virus is often destroyed there's just these two gene products left being expressed in themselves continuing to drive the development of the tumor and of course it's this stage when you get invasive carcinoma which ultimately results in death of the infected individual so what do these things look like i have to show a little bit of biology here and you know it starts to starts looking at real lesions on real people but what i wanted to show you was how what i've just shown you in a cartoon form how does it look actually in a person okay and and what i have here this is a cervix okay and on this cervix you can see there are like two two small lesions one here and another one here okay now we know that this individual is infected with HPV 16 this is the most carcinogenic biological agent on the planet okay it is it's a real real potent carcinogen and then when you look at these lesions you can see this one here which is really you know it's barely visible and so what the clinicians did they took a sample from here and made a section through it and so if you think of a vertical section through the cervix this is what you have i'll tell you what the colors are in a minute but this is the skin this is the skin of the cervix with all these multiple cells forming that protective barrier and what you can do is you can take this section through the skin and you can stain the cells these are these small cells in here with two different colors for two to answer two different questions in red what you see are cells that are dividing that are proliferating dividing the DNA what you see in green is the virus being produced it's the late the late viral gene products and what is really intriguing about this particular slide is that when you look at this you know you have you have a part of the lesion which is clearly infected in the cervix and then next to it it's normal tissue and when you look in the normal tissue you see the only cells that divide are these cells in that bottom layer of the skin which is exactly what i was telling you but when you go to the part which has papillomavirus present look how many cells are replicating DNA and that is a direct consequence of the activity of those two viral proteins E6 and E7 and then in these upper layers you're getting more virus produced which is going to go on and infect to the people this is what we will call a low grade lesion it's it's exactly what the virus wants to do it's producing more virus which will infect more people obviously this will be monitored closely if it was detected in the clinic but in this stage it's not particularly dangerous we go to the other lesion more substantive and this same virus but this is what will be called a high grade lesion this is a lesion that if it was left untreated would develop into cervical cancer and when you do that same stain you see the pattern is much different the numbers of cells that are replicating DNA is much greater the ability of the virus to replicate itself is being lost it's we're heading into that dead end stage for the virus it can't produce itself anymore and you probably can't see from this slide but within here there are what are called aberrant mitoses so that means you can see cells in this in this in this section cells that are dividing in a way that they shouldn't be so it's a baron it's it's it's bad news and so this is bad news from a patient perspective and really um someone presenting with this type of morphological appearance would need to have pump treatment and removal of the lesion to prevent development into full-blown cervical cancer so this is how we think it all works this is sort of like a summarized model of what i've shown you get infection you into this single cell here which ultimately goes through a process of amplifying genomes making new infectious virus particles and after a while the infection is resolved and we think there's very strong evidence that it enters a latent type state that means the virus probably remains in a very small amount of DNA in one or two cells which in the future may be able to reactivate and cause a fresh round of infection in some individuals we have this persistence which can last for several years morphologically they look the same we just know that it stays there for a long time and staying there for a long time means that you can get changes taking place in some of these cells mutations in the DNA which give a further enhanced proliferative capacity to those cells at that point we're looking at that high-grade lesion and which ultimately can then progress to malignancy and we know that through all of this there's a lot of we need E6 and E7 to maintain that transform phenotype and so these are really excellent targets for therapeutic intervention in HPV-induced malignancy why do we need therapies we've all heard about the vaccine if we implemented it globally today it would still take 10 to 20 years to impact on the disease there's a massive issue in terms of cost and logistics in many developing countries many many countries that iCGP works with do not have a HPV vaccination program many many countries that we work with don't even have a diagnostic program and even when they do have a diagnostic program nobody knows what to do with it i've had terrible examples in i was in Zimbabwe last year where an individual had had a biopsy but she couldn't afford to go and have that biopsy tested for HPV she carried it around in a jar two years and then eventually arrived at the clinic with full-blown cervical cancer so these are sort of issues that many developing countries are facing and we need to find ways that we can a increase knowledge of how to prevent the disease knowledge about how to go and be screened for it but also to provide better therapeutics and better access to diagnostics and preventative measures and so despite a vaccine which is probably one of the best vaccines that's available we're still seeing a massive increase in the numbers of cervical cancer cases which is really very very depressing i realized i i took a long time over that but i i hope it was quite useful to see how how where i'm coming from what i'm going to do now i'm going to skip the section on entry and i'm just going to go and say a little bit about some of the work that my lab has been doing to look at the e6 protein so this is going to get a little bit more technical but i'd like you i'd like to be able to say a little bit about the sort of approaches we're taking to try and identify ways in which we might be able to get new therapeutics so this is e6 what's drawn on here are all the cellular proteins with which we know it can interact with okay doesn't matter what they are okay that's completely relevant but what is very important to remember is that these viruses are they're very small they have very limited genome coding capacity but the proteins they encode are really multifunctional they have to do a huge number of different jobs and when you look at this and you look at the activities that these proteins are involved with and what it's linked to the virus we have activities related to obviously replication of the virus the virus wants to replicate so some of these proteins are important for genome maintenance for genome amplification for inhibition of apoptosis apoptosis is a is a process by which a cell that is infected and sees this DNA replication occurring when it shouldn't will commit suicide the virus blocks that so fine the byproduct of some of these interactions however is cancer making cells immortalized that can cause cancer in mice they can induce genetic instability so it's really it's not what the virus is trying to do but it's the byproduct of some of these associations and what my lab has been very interested in is how does how does the virus do this you know e6 is actually a very small protein it has a half life of about 30 minutes which is really quite a short period so from being produced to disappearing you know it's around for about an hour an hour and a half so it's very unstable and to get an answer to that I've chose a specific group of interactions which are all through a very conserved mechanism I mentioned at the beginning so each of these circles is a cellular protein okay they're different cellular proteins that are present doesn't matter what they are it's just to emphasize that it does it can associate with many different ones so I mentioned at the beginning about there being 300 viruses HPV types yet a very small number that cause cancer and several years ago my lab when we were working on this we realized that all those viruses that are cancer causing in their e6 protein have a very highly conserved stretch of amino acids at their c-termis and that stretch of amino acids is like a it's like a marker of oncogenic potential they're absent from the lowest viruses and so it's just those viruses that are causing cancer this motif and so we've been sort of intrigued to understand what this does and how might it be part of that cancer process so what we did with that was to take these viruses that are cancer causing we have another group that are very rarely associated with cancer and then one other group HPV 40 which is class as benign it has a very distant homology within this c-termis and what we did was a proteomic screen what do I mean by that we take these peptides we have them on a solid support we take a cell extract and we put that cell extract over this peptide and we then analyze what cellular proteins are bound how is that what are these different viruses capable of interacting with and when we do that analysis it's really quite amazing if you look at HPV 16 which is like I said the major cause of human malignancy I'm also at HPV 18 which is a very similar one what I'm showing here are all the different proteins that were pulled down from that cell extract using that single peptide so HPV 16 is incredibly multifunctional within that piece of amino acid within that sequence of protein the same is also true for HPV 18 if we go to a virus which is extremely rare in cancer it has a much much more restricted interaction profile and then this virus which has a very ancestrally distant motif it does have this ability to interact but it's just with one protein what do we think this means it means that this motif is highly multifunctional we know that it can perturb control of cell polarity so that's how a cell knows for its top from its bottom and it can perturb proliferation control and what is really quite intriguing is that the most oncogenic HPV types have evolved a much greater functional flexibility within this motif and can therefore affect many more signaling pathways is this so far removed from potential therapies well the answer is no we have structures now of these interactions and we can model into those structures compounds that may be able to block those associations so that's the route my lab has been taking in this particular part and I think it shows really emphasises a point that why some of these viruses cause cancer and some of them do not it's their ability to be modular in terms of the proteins the way they're the way they've evolved to be able to carry out so many different activities it probably originated through them evolving along with the different target cells to be to infect different tissue types but one of the consequences of that is an ability to cause cancer so that's the lab this is who we are at the moment as you can see it's pretty international and it's one of the things I really love about working in iCGb and within the development area is is the fact that you really do get to work with people from all over the world which for me is a wonderful learning experience so I was going to spend very very quickly I know I probably spent too long there so I'm sorry I will spend just quickly five minutes giving a very quick overview of iCGb before I do are there any questions on the science yeah target the the other two proteins which are which are responsible for the capsid so so the so the so the capsid what is the recognition okay so the receptor it's a really very contentious area it's proteoglycans on the cell surface there's two or three different receptors have been proposed my fear is that it's probably quite pleotropic and can interact with multiple receptors on different cell types the restriction point with HPV is not at the entry step the restriction point is gene expression so you know you can take HPV 16 and it'll in fact almost pretty much any cell you put it on to but you'll only get gene expression if the cells are differentiated okay so this is who we are I think you all know that we are global we have the labs here in Trieste which is HQ we have labs in New Delhi and we have labs in Cape Town and I would say there's about 750 people working within the organization we're growing and that's something that I'm really happy with over the last two to three years we've had a lot more interest in the organization we've got new countries joining all the time the last one to join was Rwanda and so this is something that were really very happy about obviously there's the science and as I was saying to Atish at the beginning we want to be a center of excellence for doing great research in molecular and cellular biology but it's not our sole reason for existence in fact we have to use that so that we can fulfill our mandate which is to get technologies to the countries that really need it so we have the research fellowships and in all the different areas that we work on for instance we have a large group of people working on infectious disease we have a lot of groups working on non-communicable diseases such as cardiovascular cancer I fall under I can fall in two sets I can be cancer or I can be virology so I sort of tend to move myself backwards and forwards here there's a very strong lab working on neurobiology interest there's parasitic diseases which is primarily New Delhi and virology which is spread across the whole of the organization we develop and deliver drugs to the countries that we work with through work that's done in Trieste we have work on biofuels and industrial biotechnology which is a lot of work that's been done in New Delhi and in fact we were talking just yesterday about a novel enzyme combination that's been developed in New Delhi which is going to get taken into developing second generation biofuels within India so this is really a major major contribution that the New Delhi component have made and then not to forget agriculture we have a lot of groups working on various forms of modifying crops to make them resistant to various forms of stress obviously there's big issues with climate change and of course increasing crop nutritional value is something else that we're very keen on and I should say I'm I shouldn't say this but I'm a real strong proponent of using modern molecular biology to deal with these challenges that we face in agriculture and that means developing GMOs it means doing genome editing because at the end of the day that's the only way we're going to solve those problems so we have the fellowship programs which run throughout the year we do a lot of work with women in science and we have a lot of programs that specifically support women scientists coming from lower middle income countries in 2022 we had around 400 fellows that were working in the ICGP labs which I think is pretty impressive we're also a grant funding agency so we give grants to support international collaboration and one of the things that I'm really excited by are these early career return grants where we provide research support for young scientists who want to go back home they maybe had a great postdoc overseas but they want to go back and establish their own lab and we really help them help them do that again we're supporting 102 projects in 42 different countries I mentioned tech transfer so what we do in Trieste we have a facility that can develop biotherapeutic drugs to a standard which meets that of the FDA or the European Pharmacopoeia and we transfer that technology to member countries and this can be from production of insulin it can be from erythropoietin various forms of interferon why and that's cost if you look at interferon rotheron the standard price per dose on the market is around 30 euros what we produce to the same standard is about one and a half cents that is a massive saving for a small company or a country that is what we would consider lower middle income and so this is what we do and we've been really very very I think we've done a great job over the years in ensuring that all of these different technologies are now being marketed in low middle income countries I should be taking no revenue from that we just give them to technology and they do all the subsequent marketing one of our biggest partners has actually been Bangladesh which is the least developed country and they've taken three or four of these products and are marketing them locally we also work with big international partners this is a project on pesticide mitigation in late season crops one of the big problems that they face in Africa is getting the crops to the European market because of residual pesticide content and so this is a project that we're working on to help farmers reduce that pesticide load I'm going to just finish by saying a little bit of something that we did in the pandemic which was helping labs in Africa to basically do diagnostics for SARS-CoV-2 because they couldn't access any of the reagents that were needed for diagnostics and so we teamed up with the Gates Foundation and New England Biolabs we had a product which was a novel diagnostic it was a what's called it was isothermal it was just as reliable as regular detection methods such as PCR but it was ideal in a low resource setting and that product has now rolled out and we're in a phase two situation now with further countries in Africa they're getting this technology many of them have now introduced their own regulatory framework so they can use this technology for diagnostics for other infectious agents and ICGB is now also working as being a reference center for trialling additional diagnostics in low resource settings and so I think with that yeah I'll stop at that so thank you very much okay thank you Lawrence for a very informative talk I guess there were a lot of questions are there any further questions sorry just to understand the role of the countries that are part of so being part means that they give money to there is some yeah okay so when a country comes on board there is an assessed contribution and that's based on the UN scale of assessment but with a much reduced multiplier and so what it means is that many of the countries in Africa they pay us five thousand dollars a year it's a token it's a token gesture the bigger countries such as China Brazil their contribution is a hundred and eighty thousand and that's the maximum that's the ceiling so that's that's that's what we get from the countries and so depending on where the country is on the UN scale of assessment they pay something in between those two values but not much anyway no no I mean we're very we're very we're very grateful to Italy because they are the major they are the major contributor sorry so the number of you said that you mentioned you have 700 now how many people work at icgb there's about 750 across the three it's a large number yeah it's a lot of numbers also what was interesting I just wanted to ask you from the say also it was interesting to know a bit about icgb that this program of early career it is a return grant yeah that sounds like a an interesting program which could also be of interest to our community of scientists yeah I mean it's uh you know it's it's obviously very popular um but you know I we obviously keep our testimonials from and it's been fantastic when I've traveled and and you go to a country and you meet sort of a few of the researchers and they say oh yeah I came back to Kenya whatever uh 15 years ago and I'm you know they're doing well I want to but it was it was icgb was the one who gave me my first grant you know and and that sort of thing is is is cool but does that come from your main budget or do you have some other ways of arranging this okay so when I took over we were funding um we were getting around 500 applications a year and funding something in the range of 15 okay which is the success rate is dire um this year we've managed to fund 44 and a lot of that is because of bringing in extra support to do that partnering with other partners to help support those activities um so yeah well I still I still like to get it a little higher I may mean for 60 these are supported by member states or by other donors other donors other donors that's very interesting not not not the member states do not have the money yes yes yes thank you very nice talk um I had a question about I mean we are part of UNESCO and as part of UNESCO we pay a lot of attention to open science uh of course in the context of theoretical physics I mean the economical value of what I mean string theory around even you know whether you can attach an economical except the salary of the research but I mean in your case of course as you show the the the the implications are huge I mean there are orders of magnitude the cheaper to produce them so how do you deal with intellectual property which I guess is part of the reason why these costs are orders of magnitude okay so what we've what we always do with the products that we we provide a market they're all off-patent so the patent issues have gone they've expired and that's why we can do it now many many countries that have a fully fledged biopharma setup they want the patent because that gives them protection for their investment but when you go to Africa and places where the market is much smaller and these big players they're just they're not really interested um you know small startups there are quite happy if you know they actually prefer it the fact that they don't have to worry about patent issues all they do is they take the technology and they produce we transferred last year you know even to South Africa they've taken one of the products and that should be hitting the market probably later this year so yeah but it needs the fact that they're off patent okay any other question okay I have one more question about your fellowship program yeah is it from the name of it it sounds like also you find some additional funding for it yeah I mean so the fellowships again we when when we when I took over we were supporting around it was about 180 I think per year we're now well over 400 so again we've got partners that are helping us with collaborations producing you know providing more support for the fellowship program um and it's allowed us to really expand so these are fellowships like a postdoctoral fellowships they're mostly many some of them some of them are phds some of them are postdocs and some of them are phds through a postdoc book for short term you know periods of six to nine months and we also I mean in that calculation I'm also including people that we support to go to other countries so we have a program of exchange where let's say somebody working in Bikino Faso wants to send somebody to Brazil we'll we'll support that sort of activity something we can learn from our younger brother okay thank you very much maybe you can move to the reception thanks a lot