1 00:00:01,510 --> 00:00:05,310 We start by saying your name and, of course, your titles. 2 00:00:06,510 --> 00:00:12,750 Yes. I'm Dr. Nicole Raab. I'm a visiting lecturer at the University of Oxford in the Department of Physics, 3 00:00:13,140 --> 00:00:17,310 and I'm an assistant professor in the medical school at the University of Warwick. 4 00:00:17,750 --> 00:00:24,899 Okay, that's lovely. And you before you went to you went to work in I went to work in July 2020. 5 00:00:24,900 --> 00:00:33,210 And before that you were here? Before that I was in the Department of Physics working as a Royal Society Research Fellow. 6 00:00:33,720 --> 00:00:40,290 And before that, I was a Ph.D. student in the Sir William Dunn School of Pathology, also here at Oxford. 7 00:00:41,310 --> 00:00:47,340 And your main interest during this time is being well, you got quickly got interested in viruses. 8 00:00:47,340 --> 00:00:56,850 What what is it that appeals to you about viruses? So I, I moved from South Africa when I was 17. 9 00:00:56,880 --> 00:01:00,870 I went to study microbiology at Imperial College London, 10 00:01:01,470 --> 00:01:07,440 and I quickly realised then that viruses were really fascinating and I specialised in that in my final year. 11 00:01:08,160 --> 00:01:16,350 And so when I was sort of towards the end of my degree, I was looking around for a Ph.D. and I knew that I wanted to work in viruses. 12 00:01:16,740 --> 00:01:22,620 And then there was a great opportunity to do Dphil in the Dunn School at Oxford. 13 00:01:22,860 --> 00:01:33,810 And so I was really, really lucky to be offered a dphil working with somebody called Professor Irvin Fidel, and he's an influenza biologist. 14 00:01:34,030 --> 00:01:39,240 And so I spent four years with him, which is a really super time. 15 00:01:39,250 --> 00:01:46,050 And and by the end of that, I had a pretty good grounding in molecular virology techniques, 16 00:01:46,410 --> 00:01:53,460 and I was absolutely of sold that that's what I was meant to work on and that's what I was going to continue doing after that. 17 00:01:55,250 --> 00:01:59,629 And so it is sort of slightly surprising that you ended up in that department of physics. 18 00:01:59,630 --> 00:02:02,270 How did that come about? Yeah. Yeah, it is. 19 00:02:02,990 --> 00:02:12,860 So I was looking around for for a postdoc position and this really great opportunity came up to work with Professor Kelly's company, 20 00:02:12,890 --> 00:02:15,920 this in biophysics and here at Oxford. 21 00:02:16,530 --> 00:02:25,880 And what sort of interested me about that was that they were working using something called single molecule techniques. 22 00:02:26,480 --> 00:02:30,770 And this is a relatively new field at the time. 23 00:02:30,860 --> 00:02:47,660 And when I heard about it and what it is, is and ways of studying it, rather than studying large complexes or large things like a cell all in one go, 24 00:02:47,990 --> 00:02:57,020 you isolate it, small parts of it, so you isolate proteins or molecules and you study the behaviour of just those individually. 25 00:02:57,650 --> 00:03:01,430 And, and that's, that's got a number of really great advantages. 26 00:03:01,440 --> 00:03:10,009 So if you rather than looking at the average behaviour and the average properties of millions of 27 00:03:10,010 --> 00:03:15,380 molecules in one go like you would just with the traditional biology or biochemistry techniques, 28 00:03:15,890 --> 00:03:23,150 you're able to see the individual behaviours of single molecules and that would otherwise just be lost in the crowd. 29 00:03:23,600 --> 00:03:33,560 And so, so and I went over to his lab and started learning about all of these really fascinating techniques. 30 00:03:34,040 --> 00:03:38,779 And I realised pretty quickly that not only were they really interesting on their own, 31 00:03:38,780 --> 00:03:46,340 but they're also a great way of studying small things and in particular studying viruses, which is what I was interested in anyway. 32 00:03:46,730 --> 00:03:52,580 And can you just explain how you managed to get these molecules separated out from one another? 33 00:03:52,580 --> 00:03:55,880 Because normally they'd be part of the bigger. Yeah, yeah, absolutely. 34 00:03:56,100 --> 00:04:04,730 So. So normally what you'd want to do if you if you want to study a protein, for example, which is sort of a small molecular machine within a cell, 35 00:04:05,150 --> 00:04:12,049 and you would isolate that protein and you would try to ascertain its structure so you would do something, 36 00:04:12,050 --> 00:04:16,430 X-ray crystallography or criterium, and you'd figure out the structure of that protein. 37 00:04:16,760 --> 00:04:20,330 And from that, you'd try and work backwards to figure out the proteins function. 38 00:04:20,900 --> 00:04:27,260 But techniques like that, you, you fix the protein, you take a sort of a static snapshot of it. 39 00:04:27,740 --> 00:04:32,780 And that's really informative, especially if you can sort of take a series of static snapshots of that together. 40 00:04:33,110 --> 00:04:38,479 But that's also quite tricky to do. And it doesn't give you any dynamic information. 41 00:04:38,480 --> 00:04:43,850 It doesn't show you the protein in the process of binding to whatever its ligand is. 42 00:04:43,850 --> 00:04:46,160 It doesn't it doesn't show it actually working. 43 00:04:46,490 --> 00:04:54,500 And what single molecule techniques do is they allow you to isolate that protein and look at it with a microscope in its native state. 44 00:04:54,500 --> 00:04:59,960 So you can add its ligand, you can add nucleotides to make it copy DNA, for example, 45 00:05:00,260 --> 00:05:04,510 and you can actually watch in real time as it's doing the work that it would normally do. 46 00:05:04,520 --> 00:05:09,530 So you can get a lot of kinetic and dynamic information that would otherwise be lacking. 47 00:05:09,860 --> 00:05:13,100 And how do you do that? You use a microscope. 48 00:05:13,760 --> 00:05:23,620 So so you use a sort of a customised microscope that's designed to try to look at just small single molecules. 49 00:05:24,110 --> 00:05:27,139 And and there's two main ways of doing that. 50 00:05:27,140 --> 00:05:35,720 So the first way is you take your protein of interest and you label it with a dice that can be seen on the microscope, 51 00:05:36,170 --> 00:05:41,329 and then you dilute it down to peak, very low concentration. 52 00:05:41,330 --> 00:05:48,739 So this is very, very, very dilute. And then you flow each use of flow your solution through the microscope. 53 00:05:48,740 --> 00:05:57,380 And because the proteins are so diluted, you see one at a time as they fly past you detector and the dye and the dye, 54 00:05:57,500 --> 00:06:00,770 the dye is a fluorescent dye, so it gives off light. 55 00:06:00,770 --> 00:06:07,550 When it goes past, you detect and you can see that light and you can infer things about what the proteins do from the light that it gives out. 56 00:06:08,210 --> 00:06:17,360 And the other way that that and the other thing that you can do is you can take a protein of interest, label it, and then stick it on to surface. 57 00:06:17,360 --> 00:06:25,069 If you could stick out to the surface of a glass slide and you use a microscope that then scans around the glass side but only looks at a very, 58 00:06:25,070 --> 00:06:31,970 very small area at a time. So it only picks up one or two molecules in one go, and we watch them that way. 59 00:06:32,200 --> 00:06:37,310 Mm hmm. So you began to use the same technique to look at viruses. 60 00:06:37,590 --> 00:06:41,399 What particular questions were you? What were you? Just developing the technique. 61 00:06:41,400 --> 00:06:49,880 Could you help us? Yes. So. So we realised that this this would be something that's potentially really great to apply to viruses. 62 00:06:50,370 --> 00:06:54,290 And as far as we knew at the time, nobody had even tried to study. 63 00:06:54,830 --> 00:06:56,630 When you flew proteins in this way. 64 00:06:56,900 --> 00:07:05,300 So because that was what had worked on the phone, because we had collaborators, which was my previous supervisor in the dance school. 65 00:07:05,570 --> 00:07:08,740 This is the obvious thing. Thing to, to, to try. 66 00:07:08,750 --> 00:07:17,840 So. And what we actually did in the end was we managed to carry out the first single medical studies on influenza virus. 67 00:07:18,380 --> 00:07:27,570 And so we concentrated on a protein of the virus called the polymerase, which is the protein that copies the virus genome and makes more copies. 68 00:07:27,570 --> 00:07:31,729 So you make more viruses. And we isolated the polymerase. 69 00:07:31,730 --> 00:07:42,860 And we then showed how it bound to the viral genome and how it changed the shape of the protein and when it bound to it and in order to copy it. 70 00:07:43,500 --> 00:07:52,040 And so that was a pretty exciting time. And it was a really nice collaborative project with lots of people involved and 71 00:07:52,810 --> 00:07:57,800 really exciting because we were showing things that hadn't been seen before. 72 00:07:58,520 --> 00:08:02,240 And so that would normally be happening inside the infected cell. 73 00:08:02,690 --> 00:08:10,130 Yeah, that's right. Yeah. Yeah. But in this case, you just you take that protein out of the cell, out of the virus, 74 00:08:10,610 --> 00:08:17,910 and we we stuck it down, and we then gave it a fluorescent version of the genome to bind to. 75 00:08:17,930 --> 00:08:24,980 So you could see the binding. And then by looking at the changes in, in, in the signals that you get or from the different dyes. 76 00:08:25,400 --> 00:08:32,960 And so we used something called French Way and which is it stands for something complicated bit. 77 00:08:33,260 --> 00:08:39,800 And what it does is it gives you a measurement of how far away two days are from each other. 78 00:08:39,830 --> 00:08:43,210 So if you have two days on your, you know, 79 00:08:43,280 --> 00:08:52,009 on your protein and on your RNA and that are in AIDS and very close contact with the protein then and can get very high signal. 80 00:08:52,010 --> 00:08:57,740 And if it's very weak and no signal, so and then you can actually watch that signal changing over time. 81 00:08:58,040 --> 00:09:03,380 So that's the technique that we used. And so what does that. 82 00:09:04,280 --> 00:09:17,090 Where does that give us up to in terms of time? So I would I worked as a postdoc with Achilles and from 2011 until 2017. 83 00:09:17,600 --> 00:09:21,620 And so we established the single medical system for flu. 84 00:09:22,010 --> 00:09:27,830 I had two career breaks during that time, so I had my two eldest daughters during that time as well. 85 00:09:28,550 --> 00:09:34,820 And and then that for me to the time when I was thinking about what to do next. 86 00:09:34,970 --> 00:09:44,020 And so I applied to the Royal Society for a research fellowship and which I got some started in 2017. 87 00:09:44,030 --> 00:09:48,170 So this is my first kind of independent funding to start my own group. 88 00:09:48,710 --> 00:09:57,020 I got my first PhD students and and yes, so I started setting up my own lab. 89 00:09:57,260 --> 00:10:03,590 And that's something that's sort of reflects all of the things that interest me. 90 00:10:03,620 --> 00:10:16,070 So we're a interdisciplinary group of people from all different kind of backgrounds, ranging from physicists to biologists and few things in between. 91 00:10:16,670 --> 00:10:25,190 And and I thought that what I'd like to do is use these amazing techniques that I've learnt these biophysical techniques and 92 00:10:25,190 --> 00:10:36,320 apply them to study viruses and to study how viruses replicate themselves and and also come up with ways to detect viruses. 93 00:10:36,350 --> 00:10:46,370 So from around 2015 or so and we started to think about using fluorescence, 94 00:10:46,370 --> 00:10:57,560 which is the way that we label what we're interested in and microscopy as novel ways to detect viruses and to diagnose them in samples as well. 95 00:10:57,740 --> 00:11:04,340 Is diagnosing viruses difficult? But I mean, yes, because they're small. 96 00:11:04,640 --> 00:11:14,840 So it's a traditionally virus diagnosis and it started with culturing virus in cells in a lab, which is extremely hit and miss. 97 00:11:14,990 --> 00:11:22,220 So and you know, in order to grow up the virus, you have to have it in the right conditions, in the right cells. 98 00:11:22,520 --> 00:11:30,110 You have to wait about a week to know if it's worked. And then and then you need to another way of sort of identifying that it's that specific virus. 99 00:11:30,110 --> 00:11:35,509 So. And traditionally, people turn to electron microscopy to do that. 100 00:11:35,510 --> 00:11:44,030 So you try to image what you've grown and you use sort of what it looks like to try and classify what it is. 101 00:11:44,480 --> 00:11:54,350 So you can see there's lots of probabilities of that. It doesn't happen in any timeframe that's useful clinically because, you know, someone might. 102 00:11:54,410 --> 00:12:00,920 Come in with an infection that's very serious, and then they can't wait for an entire week to know what they've got. 103 00:12:01,910 --> 00:12:09,220 And also, so technically, it's got a lot of challenges as well and it's not standardised. 104 00:12:09,340 --> 00:12:12,560 So it is pretty hit and miss. 105 00:12:13,070 --> 00:12:17,570 And so so that's sort of the history of of diagnosis. 106 00:12:17,570 --> 00:12:25,940 Of course, we have much more modern molecular techniques now, which obviously thanks to COVID, lots of people, everyone is very familiar with these. 107 00:12:26,510 --> 00:12:35,270 And so and there's PCR or PCR where you amplify up small fragments of the virus genome, 108 00:12:35,810 --> 00:12:47,720 which is the kind of gold standard for viral diagnostics and has really come to the forefront during the pandemic and which is very, very accurate. 109 00:12:48,020 --> 00:12:52,970 And that also has some downsides. So it's not particularly timely. 110 00:12:53,200 --> 00:12:57,799 It takes several hours and you need a lab to do it. 111 00:12:57,800 --> 00:13:07,160 So you need to get your sample into the lab and you need to extract that viral RNA, the virus genome, in order to carry out the assay. 112 00:13:07,760 --> 00:13:14,240 And so something else that sort of happened over the last couple of years of COVID is, of course, 113 00:13:14,990 --> 00:13:23,629 return to other types of tests that can be done in point of care at home, which is natural for assays, since they're nothing new. 114 00:13:23,630 --> 00:13:26,810 But they've never been sort of ruled out on this kind of scale before. 115 00:13:27,320 --> 00:13:39,950 And yes, so and that sort of at the start of the pandemic and even today is sort of what we have in our arsenal for for diagnostics. 116 00:13:40,670 --> 00:13:47,450 And so what I did I did interrupt you to ask about whether it was difficult to diagnose viruses, 117 00:13:47,450 --> 00:13:53,050 but he was telling me about that they and that the work that you were doing in your life when you first. 118 00:13:53,300 --> 00:14:01,730 Yeah I mean so so when we first started thinking about this, we could see the problems that they were with the technology that was available. 119 00:14:02,090 --> 00:14:10,910 And we realised that what we have is a way that you can see single viruses because this is what we'd been doing. 120 00:14:11,360 --> 00:14:21,799 And so if you can do that, then you don't need to go and take a sample and try to amplify that sample that to detect it is very sensitive. 121 00:14:21,800 --> 00:14:27,310 So you can see just a few particles and you don't have to purify anything out. 122 00:14:27,320 --> 00:14:31,130 So so we thought this could be very sensitive and this could be very fast. 123 00:14:31,760 --> 00:14:36,770 And so it's something that happened over, over quite a few years. 124 00:14:36,770 --> 00:14:43,280 But we started first with thinking about how how we can visualise these viruses in a clinical sample. 125 00:14:43,280 --> 00:14:49,100 So Heidi labelled them so you can see them and we explored lots of different ways of doing that. 126 00:14:50,170 --> 00:14:56,059 And so the way that we discovered something that was pretty exciting, 127 00:14:56,060 --> 00:15:04,310 which was that you can use and short in ways that very short labels that are 128 00:15:04,310 --> 00:15:10,040 negatively charged and remember the surface of a virus is negatively charged as well, 129 00:15:10,250 --> 00:15:13,640 and you can use a positively charged solution to bring those things together. 130 00:15:13,910 --> 00:15:17,090 And so we call this cation mediated labelling. 131 00:15:17,600 --> 00:15:20,720 Isn't that enough of a bit. 132 00:15:21,110 --> 00:15:23,959 And what we discovered was a really, 133 00:15:23,960 --> 00:15:35,210 really quick way of adding a fluorescent label to any virus in a sample a much quicker than anything else that's known out there. 134 00:15:35,660 --> 00:15:42,500 And it's instantaneous. You add your labelling solution and you put your sample into a microscope and you can see it straight away. 135 00:15:42,740 --> 00:15:46,970 So the have DNA matches the the genome of the. 136 00:15:47,240 --> 00:15:50,380 No, it doesn't know. It's just a charge base essentially. 137 00:15:50,390 --> 00:15:55,580 So that the bit of yeah. That base of DNA and it has to be it has to have some features about it. 138 00:15:55,580 --> 00:16:02,240 It has to be a certain length and it's just to maintain enough negative charge and fit. 139 00:16:02,570 --> 00:16:10,280 It's it's a universal label. So you add it and it can label any pathogen in the sample. 140 00:16:10,580 --> 00:16:15,230 Well, so why is that useful if you I think if you've got. 141 00:16:15,600 --> 00:16:23,990 Yeah. So code to that right. So so that was the first thing that that we discovered and you're absolutely right. 142 00:16:24,740 --> 00:16:34,820 So what do you do with something you've got a really good universal label for Pathogen, but how is it useful in a diagnostic setting? 143 00:16:35,210 --> 00:16:45,800 So so we actually spent the the year or two before the pandemic and trying to turn that into a diagnostic assay. 144 00:16:45,800 --> 00:16:54,230 We were focussed on flu and we were thinking of and thinking of ways that we could do a quick screen for seasonal flu strains. 145 00:16:54,300 --> 00:17:03,040 It was going around and and what we realised is that if you label your virus in a sample, you look at it on a microscope, 146 00:17:03,040 --> 00:17:11,630 you take a quick picture or two and by when you look at those pictures, they're really, really hard to tell apart. 147 00:17:11,640 --> 00:17:15,520 So you can have two different viruses. They're going to look the same by eye. 148 00:17:16,170 --> 00:17:21,900 And but if you do something clever, so if you take a computer, 149 00:17:22,020 --> 00:17:29,760 you take an artificial intelligence neural network, what you can do is you can show that network, 150 00:17:30,000 --> 00:17:38,070 the pictures you've got over to viruses to learn the features that are specific to each virus family that's in there. 151 00:17:38,550 --> 00:17:41,990 And then you go back and you shoot a third picture of an unknown virus. 152 00:17:42,000 --> 00:17:48,750 It will tell you which one it is. So that's another whole area of research, isn't it? 153 00:17:48,900 --> 00:17:53,580 Yes. Intelligence, absolutely. Yeah. Involve some collaborators. 154 00:17:53,760 --> 00:17:57,479 So this this is a complete stroke of luck. 155 00:17:57,480 --> 00:18:00,750 I had a first a summer student. 156 00:18:01,020 --> 00:18:02,940 His name is Nicholas Shyness. 157 00:18:03,270 --> 00:18:11,250 So if it's a summer student and he then stayed on and did his master's project with me in the lab and he then stayed on to do his dphil as well. 158 00:18:11,550 --> 00:18:17,310 And he was the one who his his master's project was basically bring this about. 159 00:18:17,310 --> 00:18:21,930 And and he's he's a very brilliant scientist. 160 00:18:21,930 --> 00:18:29,460 And and he managed to he he he designed the neural network and showed that it works with this instance. 161 00:18:29,970 --> 00:18:35,270 And so so we reached that this is a I've been doing that works I think it's very it's 162 00:18:35,290 --> 00:18:41,970 something that's what the word is but it's it's essentially created in a computer. 163 00:18:42,300 --> 00:18:51,360 It it's a computer algorithm that you train to recognise images of features of changes because is absolutely yes. 164 00:18:51,450 --> 00:19:01,169 So he did physics undergrad at Oxford and he knows all about maths and coding and he came up with this and so, 165 00:19:01,170 --> 00:19:09,840 so I mean we thought it was pretty exciting and, and by the end of 2019, 166 00:19:10,230 --> 00:19:16,590 we, we had shown that it worked pretty well and flew and we could actually differentiate 167 00:19:16,590 --> 00:19:20,850 flu strains even quite closely related to flu strains using this technique. 168 00:19:21,360 --> 00:19:31,710 And we'd spoken to Oxford University Innovation, which is the technology transfer company for the university about here, 169 00:19:32,460 --> 00:19:40,680 and protecting intellectual property and thinking that perhaps somebody could find it useful. 170 00:19:40,920 --> 00:19:45,989 But, you know, someone might want to license it and turn it into a diagnostic test one day. 171 00:19:45,990 --> 00:19:52,650 So that and and that's pretty much where we were when, of course, COVID started. 172 00:19:52,740 --> 00:19:57,360 So the question of asking a deputy, when did COVID start for you? 173 00:19:57,360 --> 00:20:02,010 When did you notice there was something happening and realised that you could get involved? 174 00:20:02,310 --> 00:20:06,389 And so so for me it was almost was right at the beginning. 175 00:20:06,390 --> 00:20:11,280 So I think so being a virologist I was interested in this kind of thing. 176 00:20:11,280 --> 00:20:17,280 And actually what I've been doing is I, I've been teaching pandemics and, 177 00:20:18,460 --> 00:20:24,930 and how viruses cause pandemics and to the medical students for quite a few years until this point. 178 00:20:24,930 --> 00:20:30,300 So so it was something that always interested me in that I knew a bit about. 179 00:20:30,690 --> 00:20:40,980 So, and when, you know, when the first kind of reports were coming out of some strange unknown pneumonia in China, 180 00:20:41,430 --> 00:20:45,210 I did I did read about it and I knew about it. 181 00:20:45,510 --> 00:20:50,760 And, you know, I was coming to a course and it was sort of on my radar a bit. 182 00:20:51,300 --> 00:20:58,650 And I then go completely distracted because I had my third child in January 2020. 183 00:21:00,150 --> 00:21:06,809 So so she she and she was born on the 3rd of January, celebrates science exactly. 184 00:21:06,810 --> 00:21:16,920 With the start of the pandemic. And so I did I did spend most of January thinking about other things and but still keeping an eye on it. 185 00:21:16,920 --> 00:21:25,560 And I see and I think by the end of January, it was already quite clear that this was had the potential to be something quite serious. 186 00:21:26,070 --> 00:21:29,000 And so we were already thinking then of, you know, 187 00:21:29,070 --> 00:21:37,950 our technology and what we could do and perhaps trying to see if it was something that worked for whatever this new virus was the best suited to me. 188 00:21:38,820 --> 00:21:52,710 And yes, so and what followed after that was a completely mad time where I sort of gave up any thoughts of maternity leave and. 189 00:21:54,280 --> 00:22:00,880 We we realised that I mean by the time the first lockdown happened, which was in March, 190 00:22:01,300 --> 00:22:06,820 we already realised that this was something that could be useful and could work. 191 00:22:07,210 --> 00:22:18,430 And how we knew that was that we had a fantastic collaborator at the Institute and he gave us some coronavirus samples. 192 00:22:18,430 --> 00:22:23,140 So this wasn't COVID, wasn't SARS-CoV-2, but it was an avian coronavirus. 193 00:22:23,590 --> 00:22:28,240 So the fit and that's relatively safe to handle and use in the lab. 194 00:22:28,510 --> 00:22:33,760 So the first thing that we wanted to check was whether we could actually label an image, a coronavirus. 195 00:22:33,770 --> 00:22:39,430 We haven't even tried that before. So so by then we'd done these experiments and we realised that we could. 196 00:22:40,060 --> 00:22:45,490 And so. So we knew that there was sort of something, some potential there. 197 00:22:45,760 --> 00:22:54,310 And I had a small team of people who basically dropped what they were doing to try and focus on this. 198 00:22:55,000 --> 00:22:58,000 And Achilles was really involved in it as well. 199 00:22:58,330 --> 00:23:05,230 And then what happened was there was a lockdown and basically the physics department shut completely. 200 00:23:05,240 --> 00:23:12,700 So so we were in this really strange situation where I think we were pretty much the only group in physics that was still working, 201 00:23:13,360 --> 00:23:15,370 still coming in and doing experiments. 202 00:23:15,910 --> 00:23:21,940 And but we also realised quite quickly that you were quite limited with what we could actually do in the department. 203 00:23:21,950 --> 00:23:28,960 We needed to take clinical samples and to see if there was any, if it was going to work with those. 204 00:23:29,470 --> 00:23:35,980 And so again, another of the fantastic bunch of collaborators at the John Ratcliffe. 205 00:23:36,190 --> 00:23:47,140 And so this is the groups that run the clinical and the research diagnostic labs there at Derek Kothari Group and Nicole Stokes and her team as well. 206 00:23:47,620 --> 00:23:52,950 And they very, very kindly agreed that we could take one of our microscopes to the jar, 207 00:23:53,290 --> 00:23:59,230 set it up in the research laboratory, and test COVID samples that were coming into the hospital. 208 00:23:59,350 --> 00:24:09,549 And yes, so that was a really exciting time because not many people were working, 209 00:24:09,550 --> 00:24:23,920 but we were working 24 seven and we tried it on clinical samples and SARS-CoV-2 and actually it worked and which was yeah, really exciting. 210 00:24:24,730 --> 00:24:37,180 Um, and yeah. And then in between all of that, I started to get home and I moved to yeah, moved the lab to work. 211 00:24:37,190 --> 00:24:40,989 Although most of the team still stayed here, you know, as it was. 212 00:24:40,990 --> 00:24:49,960 So it cannot sit at the time. And so yeah, it was, it was a bit of a hectic, hectic time, but also very exciting. 213 00:24:50,590 --> 00:24:59,889 And, and by and by about October time, if we had and they're good enough results that we, 214 00:24:59,890 --> 00:25:11,379 we wrote stuff into a paper budget online and and it actually it got quite a lot of attention at the time from the press and things. 215 00:25:11,380 --> 00:25:18,760 So at that point we started to think, hey, maybe there's something in here that we can actually make something that's helpful for people. 216 00:25:19,300 --> 00:25:27,190 And so that's when we started pursuing the idea of trying to have a spin out company to actually try and take the technology forward. 217 00:25:27,730 --> 00:25:35,590 And then, yeah, so the goal would be to be able to have this set up as a kind of bedside. 218 00:25:36,190 --> 00:25:43,749 Yeah. So, so if I kind of explain what it is and so we have this way of instantaneously 219 00:25:43,750 --> 00:25:51,190 labelling a pathogen in a sample and then you take that bit of labelled sample. 220 00:25:51,190 --> 00:25:56,360 He put it on a microscope, take some pictures, and then those pictures just get into the computer. 221 00:25:56,360 --> 00:25:59,200 The computer does the rest. The computer will have a quick look. 222 00:25:59,740 --> 00:26:12,729 And and so the advantages of it that you can go straight from your swab sample, you don't need to do any sort of preparation. 223 00:26:12,730 --> 00:26:16,960 You just add a bit of a label station and you can have your result in a minute. 224 00:26:17,800 --> 00:26:23,860 So it's significantly quicker than than pretty much anything else out there. 225 00:26:24,290 --> 00:26:29,979 And and also, of course, and this is still happening in a lab, right? 226 00:26:29,980 --> 00:26:38,200 So even though we have relatively simple equipment compared to hand PCR machines and extraction hoods and all of that, 227 00:26:38,590 --> 00:26:44,290 and it is still something that's lab based, carried out by somebody who knows how to operate a microscope, for example. 228 00:26:44,710 --> 00:26:50,680 And so that and you are dealing with live virus, which positively brings its own constraints. 229 00:26:50,830 --> 00:26:54,070 Absolutely. Yes. So one of the the things. 230 00:26:54,320 --> 00:27:02,690 We did it right in the beginning when we're setting up the collaboration of the JRA and was thinking about sort of how to how to go about this. 231 00:27:03,350 --> 00:27:08,270 Because what normally happens is that a subsample will come into the lab and it will 232 00:27:08,270 --> 00:27:13,040 be inactivated immediately either by heating it or a chemical inactivation step, 233 00:27:13,040 --> 00:27:17,090 because what you want is just the irony of the virus for PCR. 234 00:27:17,910 --> 00:27:21,319 In our case, what we want is not just the RNA. 235 00:27:21,320 --> 00:27:28,400 We want to see the actual virus particle. And so those inactivation methods are no good for us. 236 00:27:28,820 --> 00:27:33,500 And so so what we needed to do was come up with a new way of inactivating the virus that 237 00:27:33,500 --> 00:27:40,820 still left the virus particles intact and obviously rendered the sample safe to handle. 238 00:27:40,940 --> 00:27:45,530 Because you don't want to be doing all of this in a sealed three, that's a containment level three lab. 239 00:27:46,130 --> 00:27:50,810 And so, again, so grateful to so many great people at the time. 240 00:27:51,200 --> 00:28:04,220 And we had some some a group in the recipient, Petya, in France, who actually had a high containment facility and a microscope within it. 241 00:28:04,520 --> 00:28:09,470 And they agreed to test inactivation method for us. 242 00:28:09,980 --> 00:28:17,270 So and we did that and we actually came up with a method of fixing the virus sample so that 243 00:28:17,270 --> 00:28:22,070 it still maintained the virus particles within within it became completely non-infectious. 244 00:28:22,730 --> 00:28:31,790 And we needed to convince the University Safety Office that this is a good idea and which they did and did agree to. 245 00:28:32,180 --> 00:28:37,040 And then we were allowed to carry on with that, the clinical samples. 246 00:28:37,670 --> 00:28:41,810 And so there was a whole a huge team effort from three different people. 247 00:28:41,820 --> 00:28:50,300 And I should also mention that we say we needed a microscope to take to the to the the hospital to work with. 248 00:28:50,750 --> 00:28:57,790 And because the biochemistry department was shut down because of lockdown, they actually had a microscope imaging facility that wasn't used. 249 00:28:57,800 --> 00:29:01,050 So they agreed that we could take that microscope to the data. 250 00:29:01,070 --> 00:29:07,790 So there there. Absolutely. This so many people that all came together to to make that happen. 251 00:29:08,510 --> 00:29:17,180 And yeah, so we we had a method where the samples would come in and then you just add a 252 00:29:17,180 --> 00:29:22,700 fixation reagent and then they were safe to use in a lower containment laboratory. 253 00:29:22,700 --> 00:29:24,380 Didn't need to be done in the high containment. 254 00:29:25,580 --> 00:29:34,489 And however, you don't need to do that if you just have the sample and just contain it in a little capsule and it just gets image within that, 255 00:29:34,490 --> 00:29:46,010 which is something that we do now. So it's a so the purpose of the the spin out company is to try to move our assay from something that's done at a 256 00:29:46,010 --> 00:29:53,840 lab bench to something that can be done anywhere and hopefully give you a quick accurate results in just minutes. 257 00:29:54,980 --> 00:30:02,770 So have you you haven't actually tested it in a in a clinical setting, even in with the lab based one? 258 00:30:02,780 --> 00:30:06,200 I mean, you've you've tested it to show that it works. 259 00:30:06,320 --> 00:30:09,320 Yeah. But you haven't had doctors actually using this method. 260 00:30:09,320 --> 00:30:12,960 No. So this is something that the company is now taking for it? 261 00:30:13,550 --> 00:30:20,150 Yeah, we haven't done that. So at what stage is the company when was the company set up and where is it? 262 00:30:20,540 --> 00:30:25,360 So we had the idea back at the end of 2020. 263 00:30:25,370 --> 00:30:34,850 It took us a year to raise the funding for it so that the company is officially incorporated at the end of 2021 as what's it called? 264 00:30:35,150 --> 00:30:39,000 And it's called acoustics. And that's how you pronounce it. 265 00:30:39,140 --> 00:30:44,300 Just outside diagnostics for short. 266 00:30:44,780 --> 00:30:55,030 Yeah. And yes. So so it's only been here a short time, but we've already managed to actually build up a really great team of people. 267 00:30:55,070 --> 00:31:00,740 And what's your role within the company as I'm founder, director and I work as a consultant as well. 268 00:31:02,090 --> 00:31:06,140 And you do that alongside your work or do you? 269 00:31:06,470 --> 00:31:11,000 Yes. So it's been a very busy few as the three of us at the moment. 270 00:31:11,270 --> 00:31:16,460 And number three, I have three children that are nine, six and two. 271 00:31:17,060 --> 00:31:20,480 Yes. Yes. So not a lot of free time, but. 272 00:31:21,710 --> 00:31:29,540 Yeah. And I guess it's an exciting time to be involved in things like that. 273 00:31:29,540 --> 00:31:41,060 And and you just motivated by the fact that hopefully one day we can come up with sort of better alternatives for testing that give quicker results 274 00:31:41,330 --> 00:31:51,320 and aren't linked to expensive labs to something that could potentially be useful in other settings where that kind of facility isn't available. 275 00:31:51,350 --> 00:32:00,620 Is the microscope not too expensive? So the microscope is the lab based microscope, of course, is expensive, but you don't need that. 276 00:32:01,130 --> 00:32:05,450 You can use it for much cheaper and simpler alternative as well. 277 00:32:07,370 --> 00:32:13,130 So what's hurdles in front of, you know, when you get to the point where you can actually. 278 00:32:13,850 --> 00:32:23,629 I've learned a lot about spin ups in the last few years and what's different about working for them. 279 00:32:23,630 --> 00:32:31,580 What essentially it's the financial sector. Yes. So it's a bit of a baptism of fire because I knew absolutely nothing about it in the beginning. 280 00:32:31,580 --> 00:32:38,660 But latterly, actually Oxford as a university, a fantastic support for that kind of things. 281 00:32:39,260 --> 00:32:46,430 Not only have they got a UI who have helped us every step of the way, but they've also helped us with internal funding. 282 00:32:46,700 --> 00:32:50,779 So it pre translational work, that kind of thing as well. 283 00:32:50,780 --> 00:32:59,900 So we haven't at all been alone. We've been helps a lot, very grateful to the university and everyone that has helped us. 284 00:33:00,560 --> 00:33:09,830 And so I think the the knife of a spin out, it's a continuous cycle of raising funding to reach the next stage. 285 00:33:09,830 --> 00:33:15,620 And so that will be the next hurdle that we'll need to cross. 286 00:33:15,800 --> 00:33:19,430 And I do need to demonstrate something else. 287 00:33:19,430 --> 00:33:27,890 Absolutely. And then, you know, we're going we're progressing down the road to actually make a commercially available product. 288 00:33:28,160 --> 00:33:34,100 So there's all sorts of hurdles along the way. And we need to show that our product works and it works well. 289 00:33:34,190 --> 00:33:40,190 We'll need to get regulatory approval for it and have you go to a factory. 290 00:33:40,190 --> 00:33:49,849 What do we do? We've got some some it's a commercial company space and the with Centre for Innovation that continue. 291 00:33:49,850 --> 00:33:52,880 Yes, right. Yes. Yes, I did support that. Yes. Yeah. 292 00:33:53,660 --> 00:33:58,730 And and and various kind of business partners and stuff as well. 293 00:33:59,100 --> 00:34:06,320 And we do some aspects of it so and. 294 00:34:09,930 --> 00:34:17,010 And this. Yes. So this includes both the the labelling, the microscopy and the like aspect. 295 00:34:17,040 --> 00:34:21,300 Yes, it does. Yeah. Yes. So it was also still under development as it will. 296 00:34:21,780 --> 00:34:29,879 Yeah. Yeah. I don't think we're anywhere. You know, we're not near the final complete product, so we still definitely have an R&D site. 297 00:34:29,880 --> 00:34:33,630 And yeah, my lab is still working on aspects of this as well. 298 00:34:33,810 --> 00:34:38,540 Um, from an academic interest point of view, when you say my lab, yes. 299 00:34:38,550 --> 00:34:46,530 Do you mean do you still have a lab here? So I still have is I did one like we all went lab. 300 00:34:46,590 --> 00:34:56,340 Yes. We were trying meetings and things, but I have two students and a postdoc and two master's students who are based at Oxford still. 301 00:34:56,970 --> 00:35:00,180 And as well as the people that are based primarily at work. 302 00:35:00,300 --> 00:35:05,700 Mm hmm. Mm hmm. So. 303 00:35:08,890 --> 00:35:11,440 So yes, going out, it's changing tack slightly now. 304 00:35:11,840 --> 00:35:20,680 And how did working in lockdown impact on what you were able to do quite apart from the fact that you were supposed to be on maternity leave? 305 00:35:22,090 --> 00:35:29,320 Yeah. So so I think, yeah, in some ways we were really lucky that we actually could carry on working. 306 00:35:29,350 --> 00:35:32,050 I really feel for the people that, you know, 307 00:35:32,860 --> 00:35:39,650 the labs just got shut down and actually students and staff that couldn't access the labs and couldn't do the work. 308 00:35:39,670 --> 00:35:47,550 So at least we were able to keep going. And yeah, that was really good, obviously. 309 00:35:48,700 --> 00:35:56,350 And personally, I think a challenging time for everybody trying to work under those conditions and 310 00:35:56,860 --> 00:36:01,160 you're trying to really get things done as quickly as possible kind of thing. 311 00:36:01,210 --> 00:36:11,740 But yeah, they're all they're all great. The whole whole team, the kids and everyone else and students, people working the lab, fantastic. 312 00:36:11,980 --> 00:36:18,820 And I think there was a real kind of a feeling of collaboration and working together 313 00:36:18,820 --> 00:36:22,960 and people helping each other out and so trying to do something for the greater good. 314 00:36:23,650 --> 00:36:27,340 So that came out of it. That's interesting. A lot of people have said that. 315 00:36:27,370 --> 00:36:32,770 Yeah, I do. Did you feel that that was distinctively different from the way academic work normally happens? 316 00:36:32,800 --> 00:36:44,260 Yeah, I think so. I mean, so I think I've been at Oxford a long time before that and there was always a a good collaboration. 317 00:36:44,260 --> 00:36:51,610 You know, people, networks and people work together, but nothing on the scale of what happened due to COVID. 318 00:36:51,610 --> 00:37:01,030 I think that there was really a sense of everybody coming together and nobody was sort of out to do it too, 319 00:37:01,480 --> 00:37:04,510 because they wanted to publish a paper or anything like that. 320 00:37:04,510 --> 00:37:08,980 Everyone was doing it because it needed to be done and trying to help each other out, 321 00:37:09,160 --> 00:37:15,450 providing samples to each other for us, people, helping us by learning us and microscope things like that. 322 00:37:15,620 --> 00:37:19,930 And so so definitely that that's true that that happened. 323 00:37:20,470 --> 00:37:24,340 And do you think any of that will survive in a post-pandemic era? 324 00:37:25,630 --> 00:37:29,230 I hope so. And like, it's a good way to get things done. 325 00:37:29,380 --> 00:37:33,910 Yeah. Yeah. So, I mean, I suppose what it's shown is that that can happen. 326 00:37:33,910 --> 00:37:41,800 And these huge interdisciplinary efforts to solve problems that COVID has has through not I. 327 00:37:42,170 --> 00:37:46,510 I don't think they will disappear any time soon. And I think that, in fact, you know, 328 00:37:46,510 --> 00:37:55,479 there's sort of funding being poured into it and things for groups to work together and try and solve problems that are still not going away. 329 00:37:55,480 --> 00:38:00,790 Right. Things like long pavement, things like that that still need to be to be worked on in research. 330 00:38:00,790 --> 00:38:06,339 And so. So. So I think for you personally, 331 00:38:06,340 --> 00:38:15,159 people personally who researches they've seen how how quickly things can work if everyone comes together and is focussed on one goal. 332 00:38:15,160 --> 00:38:19,360 So I think that will change how people kind of put it together I think as well. 333 00:38:20,230 --> 00:38:25,740 You did mention in passing that you're involved in teaching. So how was that impacted by and. 334 00:38:25,900 --> 00:38:36,690 Well, I mean, so so we all learned very quickly how to do teaching online, which is not nearly as fun as teaching in-person. 335 00:38:38,320 --> 00:38:42,219 But yeah, I mean, it was just just how it had to be. 336 00:38:42,220 --> 00:38:47,290 Right, is just something that we had to do and. Yeah. 337 00:38:52,090 --> 00:38:55,030 And did you again, this is just something I've asked everybody. 338 00:38:55,030 --> 00:39:04,719 Did you were you personally did you personally feel threatened by the possibility of catching the infection or that people around you might do so, 339 00:39:04,720 --> 00:39:09,580 people close to you? I think before there was a vaccine, definitely. 340 00:39:09,970 --> 00:39:13,090 I was I was scared for my parents. 341 00:39:13,090 --> 00:39:18,540 We didn't see them at all. And the benefits of it? No, they're not that they live not far from us. 342 00:39:18,550 --> 00:39:24,940 And normally they help me out massively with looking after my children and I really rely on them for a lot of help. 343 00:39:24,940 --> 00:39:30,220 And I was too scared to to see them, especially because it's going and working in the jail. 344 00:39:30,640 --> 00:39:37,240 So. And yeah, actually, the diagnostic laboratories in the jail are on the seventh floor. 345 00:39:37,240 --> 00:39:40,440 So you have to either go in the lift or walk up seven flights of stairs. 346 00:39:40,450 --> 00:39:44,160 So there were definitely times I felt pretty vulnerable doing that. 347 00:39:44,270 --> 00:39:55,620 And, and so I didn't see them. But it was also just a time when it would have been great to have some extra support children and, and stuff. 348 00:39:55,630 --> 00:40:02,440 So. So, yes, I did. I think that vaccine coming along really changed that. 349 00:40:02,440 --> 00:40:06,550 So as soon as we were vaccinated that. 350 00:40:07,750 --> 00:40:16,180 Much more relaxed about it. But definitely for that first year I was worried about I was worried that the children get insane and. 351 00:40:16,510 --> 00:40:27,319 Yeah. And. So do you think the fact that I mean, obviously it was a worrying time, 352 00:40:27,320 --> 00:40:33,620 but do you think the fact that you were working on a problem that could potentially help help to support your own well-being? 353 00:40:34,260 --> 00:40:36,010 Definitely. Yeah. Yeah. 354 00:40:36,050 --> 00:40:49,010 No, it it so it wasn't a very easy time actually thinking that you might be doing something that even a very tiny thing to try and help you, 355 00:40:49,040 --> 00:40:52,190 but that that's kind of what drives you to do it. 356 00:40:52,340 --> 00:40:56,390 So, yeah, definitely. And what sort of animals were you doing? 357 00:40:57,290 --> 00:41:10,159 Who said, yeah, we were, you know, at one stage we were doing very, very long hours and here we went without stopping basically. 358 00:41:10,160 --> 00:41:15,200 And that the whole of the whole of 2020 is pretty much a blur. 359 00:41:15,260 --> 00:41:25,280 I don't remember much of it, but they didn't want an owner to say, well, say, yeah, it was a small baby, not the most sleep. 360 00:41:25,730 --> 00:41:35,150 And so I'd often just work at night when the kids were in bed and stuff quick, like through the night and big. 361 00:41:35,600 --> 00:41:40,580 I mean, I'm not the only one who went through that. In fact, I'm sure people went through a lot worse than I did. 362 00:41:41,090 --> 00:41:47,890 And I think I think, yeah, for people that are on the front line of it, this is scientists working on the vaccine and stuff. 363 00:41:47,900 --> 00:41:51,950 I can't even imagine what they've been through. And so and yeah. 364 00:41:53,380 --> 00:41:57,100 So again, this is a side question. 365 00:41:57,310 --> 00:42:01,030 Has the work raised new questions that you were interested in exploring? 366 00:42:01,390 --> 00:42:02,360 Yeah, definitely. 367 00:42:02,380 --> 00:42:11,770 I mean, I think we have a general interest in improving diagnostics and trying to come up with better ways and quicker ways of doing it. 368 00:42:11,770 --> 00:42:17,470 And, you know, was thinking about states. And the only thing that we have on we've got other projects in the lab. 369 00:42:18,510 --> 00:42:29,280 And I think if anything has just just cemented my my aim of trying to come up with better, better ways of doing things in PET before. 370 00:42:29,440 --> 00:42:36,910 So that's something that we will continue to, to, to, to chase after as much as we can. 371 00:42:37,390 --> 00:42:46,510 And do they have a translational focus? Some of them might are the ones that a I think that everything we do is to try and understand 372 00:42:46,510 --> 00:42:53,350 more about viruses and how they copy themselves and how they interact with host host. 373 00:42:53,350 --> 00:42:57,730 And the thinking behind that is that everything that we learn, 374 00:42:58,000 --> 00:43:04,719 every little bit of information there helps us to come up with a way to target them or make a drug 375 00:43:04,720 --> 00:43:12,430 that works against that particular aspect of it or is in a new way of of seeing that particular part. 376 00:43:12,470 --> 00:43:18,520 So I think everything we do is driven by a desire to have something concrete out of it 377 00:43:18,520 --> 00:43:24,970 that will eventually help us with all the challenges that the viruses and pandemics bring. 378 00:43:25,630 --> 00:43:34,840 And yet. And has the experience of working through the pandemic changed your attitude to work in any way, 379 00:43:34,860 --> 00:43:38,680 and what other things you'd like to see change in the future? 380 00:43:44,570 --> 00:43:55,520 I suppose it's just been it's been very busy in a period of really, really hard work, but it's not something that I would have chosen not to do say. 381 00:43:56,030 --> 00:44:03,230 And I don't think there's anything that I would change if it was happening in mine. 382 00:44:03,830 --> 00:44:07,630 Yeah. Good. Did that answer the question?