my lab is currently structured so that we have a technician and we have four other individuals there are two post doctoral fellow and we have one graduate student and there's one undergrad he's doing a summer research project and all of whom i've been incredibly impressed with and it's really it's great to work with that one of the basic aspects of what we need to do is to grow viruses to see how well they grow or how well we can keep them from growing and that involves keeping the stocks of the virus which we'll keep at a very cold temperature until we need them will then bring them out we'll bring them into a tissue culture room which is a room where we have a great deal of safety precautions a great deal of safety equipment that allow us to work safely with the virus we grow the virus on cells that grow into culture the virus again as i had said at the beginning can't grow on its own we need to have cells that it grows on and so one of the things you'll see is somebody putting virus on to cells so that we can determine how well that virus is growing either in the presence or absence of a small molecule or to figure out what happens when we've removed a component of the cell to see if the virus needs that cellular component in order to to work properly in our lab when we grow viruses we need to test a specially contained environment so we put them in different vessels like the plague so that we can see how well the virus can grow and in fact and determine if we can block that infection using our drug we put ourselves in incubators and special conditions where they can grow really access individual viruses in their right to autoclave is the way that we sterilize all of the waste that comes out of the lab so anything that has viruses or cells in it to make sure that doesn't get out to the environment is put in a lot of places and out of place is basically a very hot oven that gets very hot and also has very high pressure and steam so it will kill everything inside the bag that we put in here we also put in indicators to make sure that the autoclaves are actually working and that they kill and have the high enough pressure and steam and there's nothing alive left in the bag  see here that it's it's a very large area we slide bags of our waste in it goes for about an hour and when it's done everything is safe to go into the trash to proteins change in the cell during infection and in order to do this we have to break open cells and then look at them individually and that involves the gel that jake is running how well viruses grow and essentially what you'll see them doing is they will have put a small amount of virus on two cells growing in tissue culture and then they waited a little bit and then at the end of that time they stay in the live cells so that they turn purple and in cases where a virus is gotten into a group of cells and killed them off there'll be a little hole in that purple staining which we call plaque and that's an indication that there was a virus that came in and it killed those cells and that gives us an idea of how much virus is there the more little holes there are in the purple staying the more virus there was the fewer the less fires there is and that gives us a way really quantitate how much viruses grow if we think we were killing the virus off how well did we do if you're a bacteria you are able to live on your own almost really what you need is food if you're a virus you need to take over something else and it's that aspect of being a pair and obligate parasite requiring getting into somebody else's cel and taking that over that is one of the things that interest smile and how does this happen what is what is it that the fires of figured out that make them so successful in getting in and succeeding and but also in another aspect are particularly interested in understanding what happens when ourselves when right because it's a real competition if the virus shows up and tries to get in the cells going to answer it really rather you not be and so how is it that that battle gets fought and how is it the one i think is going to think we're really interested and one of the things that we've probably all noticed is in the last you know three four years it seems that every eighteen months something like that there is a new virus that is of concern and so then the question is where are they coming from and i think my answer to that is best stated is a lot of these viruses were probably here in that they were infecting some other animals and we see them now as infecting people because these viruses have picked up a new trick they learned how to now infect a different animal that animal being on us and as we have an increasing expansion of humans into places where they weren't previously in contact with animals that they weren't previously in contact with this will probably continue to happen and not but i also think even if we weren't expanding this might still happen we spend a lot of time with different animals and we grow pigs who grow chickens and there are viruses that come from those animals that figure out a way to begin infecting on earth in a way that is harmful and so i i see that as something that will very much continue to happen not only in the near future but continually throughout force in the foreseeable future how the virus penetrates the cell is usually it puts a protein on the outside now the cell brings the virus in once it has been brought in the virus and uses that protein to sensually fused to the inside of the cell and release all of its contents so essentially it's discovered a way to bring a key opens the door to the inside of the cell when viruses have a key they're looking for a very specific law right and so what that means in our cells is that the cells are making a protein that they're putting on the outside of ourselves and in hiv for instance the the virus is looking for two separate proteins and there are cases where there are people that l one of those two proteins in that circumstance viruses cannot get into cells because part of the lock that they're looking for no longer exists and so that's an example of how sort of this development of the virus to look for a specific lot humans can develop mutations that make them now immune to these viruses so how do people get viruses is very difficult question to answer because there's not just one way right there are a lot of different ways that viruses and up traveling and one is they'll come through insects right so mosquitoes are well recognized as things that transmit viral disease and things like hanging things like west nile mosquitoes carry them and essentially they are a very good machine for taking a virus and injecting it into our bloodstream and so that's one way that this can happen there's other way or other viruses that have gotten very good at being transmitted just by off so norovirus is you'll know the regularly events on sailing ships and things like that where spread very very quickly because it has developed a way to be very easily transmittable between people flu is another example that's fairly easily transmittable it appears to be able to be very easily but then there are other viruses that are actually really difficult to catch things like the new middle eastern corona virus that one does not seem to be very easily transmitted viruses like ebola and marburg which have a very high if a taliban rate do not seem to transmit really easily you really need to have sort of direct fluid contact and so it's not something where there is really a one size fits all answer it depends on what the virus is how it gets transmitted so what it what is global travel going to do to virus based infection and i think we're seeing it now right in the fact that the sars corona virus went from an index case in china to around the world fairly quickly to the fact that now the middle east respiratory corona virus initiated in the middle east but now there have been cases that have been transferred in various different area and so i think that's going to be something that will continue to be a challenge if this world is going to be connected more and more biplanes and rapid transit viruses that go along with us i think that is one of the reasons that continuing to do research understanding viruses and developing therapies and vaccines is important because i don't think we're going to get rid of this event of new viruses coming new virus is spreading what happens when it is the middle east and there is an annual hodgin lots of people come from around the world to a place where it's known that the virus is hanging out here or sort of tempting fate if you don't prepare for that to happen so how fast the viruses mutate they need to really quickly and in if if you work to compare to bacteria i don't know that there is really a fair direct comparison but influenza is an excellent example of viruses that are very good at mutating in an incredibly rapid manner when anti virals are induced there's a very rapid timeframe of development of resistance so this is i think this is going to be something that is very significant and is going to going to continue to be a problem one of the reasons we're looking for how do you develop good small molecules is this is i think going to be a constant question of how do you do this one one is developed it will be it will work and it will probably be very successful at limiting disease and making people feel better but it's not a permanent solution it's going to be a step on the path of continually finding new tools much in the same way that hiv was the has been sort of the most effectively treated with multiple different molecules at the same time so the two main workhorse fires is that i work on in the lab one of them is called physical or stomatitis virus i often call it horses and sometimes pigs can contract it but one of the reasons we work on it in the lab is one it's very safe for us to work with because it's not something that i'm worried that my lab workers will get or that will be transmitted out into the community but it looks a lot like a number of viruses that do cause disease it's a cousin to rabies there are a number of viruses that it looks very very similar to and so understanding how v s e works allows us to then extrapolate to these other viruses without directly having to work with them and so that's one of the viruses we work with another virus that we've begun to do a lot of work which is called vaccinate is the virus that was used as a vaccine to it was essentially the the founder virus for the concept of vaccination but it was used to eradicate smallpox from circulation on this planet and currently the only example of a vaccine program that's completely obliterated a virus from circulation and we've been studying this virus because it's similar to well it's similar to smallpox was eradicated but it's similar to other pox viruses that are still circulating one of which is monkeypox which is endemic to africa and cases appear to be strongly increasing in the last few years as the smallpox vaccination has waned and so we've been studying saxony and to try to understand you know what are the cardinal weaknesses of how this virus makes copies of itself so that we can apply that to things like monkeypox and again we're very and because we see it as a safe laboratory virus that we can do a great deal of work with that can give us a lot of information about the true human pathogens without really endangering the workers and things like that and so we've done a lot of work with those viruses and it's sort of taken a couple different approaches and one of the things that my lab has had some success with is we've been trying to find small molecules that we can use to disrupt viral replication right out of the viruses get in and replicate is one of the things we're interested in but the reason we're interested in that is we want to then come in and break those processes once we understand it how do we define a tool that we can use that blocks that from happening and so recently we found a couple small molecules one of which hits the v s e type viruses that i talked about and there's a small engine that this virus makes that makes copies of its genome and so we are finding small molecules that block its function and it can't make copies of his genomic can't make larger numbers of copies of itself and we're doing that not only for that virus but also for pox viruses where we're looking at these engines and trying to find you know things to block it trying to find wrenches to throw in in the works so that it really doesn't work very well one of the reasons that vaccines have worked so effectively for viruses i think is that vaccines have vaccines are making use of your own immune system right there making use of you know your body's natural adaptive ability to come up with things that will now fight a virus and so essentially you when you put together a vaccine and your body is exposed to it your body looks at parts of an infectious virus and makes defenses against it and it will often make defenses against multiple parts whereas say a small molecule really probably only targets a tiny little piece your immune system might be targeting four or five totally different areas within the virus and trying to block it that way and it's much much harder to evolve away from a five pronged attack than it is from a one single pronged attack and i think  vaccines often benefit from that type of approach a similar approach we've been taking is slightly different where we've been trying to address the question of in the case of serious diseases things with very high mortality so these would be field viruses like ebola and marburg where mortalities can be sixty percent whereas flu mortality is much much lower closer to wander point one percent in the cases where somebody very a virus that is associated with high mortality one of the questions is who else might that person have come in contact with that would also have this disease and with those diseases the thing that we know best is there are some treatments that look like they could be effective but they're much much more effective the earlier you give them so we've also been looking at understanding how people's immune systems are responding to try to identify if we can track infection before you feel sick right to see if your immune system is giving you signals say  you i've been exposed to this disease in a way where you are not yet clinically sick but you clearly have been exposed that would allow us to really put a jump on starting treatment right so the near neighbors of somebody who you know is infected can you test them now and tries them for ok you should probably get some treatment you look like you don't need it and so that's one of the other things that we've been doing that involves a great deal of computational analysis a lot of looking at the entire expression patterns of immune cells to identify a few genes that are these canary in coal mine these sentinels for identifying techniques to analyze a bunch of data and come up with interesting patterns that tell us what type of virus a person is infected with so for example here i'm analyzing different types of viral infections with microarray a has forty five thousand probes and each probe has a fluorescent tag and depending on the color of that probe we measure the amount of expression so all of these little dots represent an individual probe and they call that are in the case the amount of expression that probe has with correlates with the amount of expression that a specific dean has so have a higher expression that the green and then we can generate a type of the sense upon similar information so here i'm showing twenty four samples ways to detect fires and finding the idea is we want to make diagnostics as simple as possible and currently a lot of the technologies that do the best diagnosis require a lot of preparation require you to take a sample and make nucleotides from it and then you need to amplify those nucleotides and by doing that you can identify the infectious agent you can identify what's making you sic are looking to make silicon based chip with simple sort of l e d based detector where now weakens just flow blood or serum over that chip and if there's a virus present it will get captured it will get visualise and we can say aha we can see that what you have looks like influenza and that can speed treatment and the simpler it is the more likely it is to become point of care something that can be very simple to use very simple to understand the results to and so that's something that we are currently working on and in the laboratory you will see one of the prototypes that we have constructed where essentially what we've reduced it to is a fairly small instrument with a very tiny chip where we can just place the chip on their reader hit go and the reader takes care of analyzing that diagnostic chip and telling us what viruses are present what viruses are not present and one of the things that's really an advantage of this technology is we can ask several questions at once so we can say we're now looking over say ten viruses twelve viruses do you have any of these and might you actually have a couple of these because that would change how you would treat someone who's sick if you can determine that it's one or two and not encounters a cell and tries to get in and the cell actually recognizes it and shuts it down how does it do that if you look at a cell i'm using a microscope you can see it developing a certain type of response so what will happen is it will move proteins around in the cell proteins that had been sort of diffuse they were really anywhere in particular will all the sudden begin forming physical cages around the sites of virus replication and shutting down virus replication and so we've been very involved in using my cross copy and looking for various different proteins which involves using various different labels at various different colors in order to look for where those things go and where do they go relative to where the viruses and identifying what those proteins are and you know what they're doing we're looking for ways to stimulate that so that outside of a six outside of the lab we can find ways to make that natural defense much more enabled much more capable and in a sense that would be a really nice way to fight viral infection if you can just sort of wake up a le your body and say you know now it's time to turn on because we're pretty sure there's a virus or so this is a fluorescent microscope we use this to image cells that are been infected with viruses and we're able to do that by not not only using live virus to see how it enters the cells and propagates throughout the individual cells and spreads throughout cells the slot in the cover slips that these are grown on on to glass lives and their mounted directly into the microscope look for some specific proteins that we're interested in studying how they relocate lives within the cell so we typically capture a sequence like this of all three of the channels and then layer them together later and posit you can see that it's been colored so that the nuclei are blue the cells are green and then the infected cells are the red ones and we can actually look at the shape in the localization of those viruses to compare what are different treatments are doing