Kills and is your fellow UPS and Cross College Oxford and professor in biological physics at university.
Welcome to some crosscurrent shorts. Can you describe your way of doing biological physics?
Sure. Let's consider what biological physics is in the first place.
Biological physics is the application of experimental,
computational and theoretical methods to study various biological systems that can be entire organisms or it can be biomolecules.
So the approaches that we have in my love involve high end optical microscopy.
That is combined with modelling and imaging image analysis, as well as conventional biochemistry that supports the biophysics work.
And the organisms that we study are severe and viruses.
We're very interested in the influenza virus and more recently, coronavirus.
And the specifically the systems that we are studying are protein machines that are involved in gene expression and in DNA repair.
That's why we actually call factionally our lab, the Gene Machines Group, because we'd like to work on machines that like to work on on DNA and RNA.
And the main microscopy method that we employ is a single molecule, fluorescence, imaging.
So we have ways of tagging our molecules of interest with fluorescent probes.
And then we look at their at their motions in a way that that they can inform us about.
There are mechanisms both in in cells and also in purified systems.
So just to run quickly through the main approaches that we use in the group,
we perform a lot of experiments with purified systems where we take a protein machine of our choice.
For example, the machine that copies DNA into RNA, that's a protein called RNA polymers.
We can put Fersen probes on the machinery or the DNA and then walks how it's being copied into RNA.
And then by looking at the motions of the protein machine and how the DNA is is reconfigured during the process.
We understand about the mechanism.
Of course, when we do this, we also illuminate ways to stop the machinery of pathogenic versions of this protein machine.
And if past few years we have been moving this single molecule methods inside the living cells.
So we have ways, again, of labelling those protein machines of interest and then visualise how they function inside single bacterial cells.
And because we have also very powerful ways of of localising these protein machines,
we can use this this power in order to break the diffraction limited microscopy and get very detailed images of high
resolution of this machinery and also other interesting structures in inside cells in order to be able to achieve these.
So clearly,
you have an interdisciplinary group that provides expertise both from the physical and biological side of the questions that we'd like to address.
We also built our own microscopes and and also the software that's needed to operate them and analyse the images.
And also we use the understanding of this machinery and the powerful microscopes in
order to be able to come up with ultra sensitive assays that can detect pathogens,
bacteria or viruses very sensitively. It's now mid-January 2021 and the UK is in its third COGAT Munchy locked down
a covered 19 has changed since everybody to the four corners of the globe.
How is it done so for you and your work? Well, obviously it has been a massive change, says for every one of us.
An entire society has felt the brunt of the of the pandemic.
But during the first leg down, we go back to March.
Part of my team was the only group that was still performing experimental work in the physics department to work on a rapid test for SA v two,
while the rest of my group was performing mainly computational work and developing software pursuing writing projects from home.
Clearly, that was a very challenging time because I had to balance many responsibilities
directing Colvard related research to keep every body engaged and upbeat,
supporting people who were not working on the coffee research and were stuck at home
while also completing my role as an examiner and also dealing with child care.
Since I have toddler twins and having them at home during the first lookdown was was clearly a challenge.
So I've been working from home for the past nine months and.
I've given up my my office in order to lower the density in my group and allow more people to work and have some some some office space,
additional office space. And of course, if I go back to July, when we're allowed to do experimental work again,
we had to work hard to establish Calvet safe protocols, both as a lab and as a department.
And the way we manage to operate quite effectively was by dividing the team into a green team and a red team,
and therefore we're operating with 50 percent capacity. That still allowed us to have a good pace of research.
But there's still many, many challenges present. For example, it's quite challenging to train new students that coming into the group,
because clearly we need to to ensure that we we keep our social distancing protocols while training students to do experimental work.
And it's hard to also assimilate them in the lab culture since the lab is operating in this kind of strange way and also teaching is done on line.
And we had to adjust our procedures for for the examination period during the treaty term as well because of coffee
and other types of impact that clearly they're not physical meetings anymore with colleagues within my my lab.
So within physics and more broadly within the biophysics scientific community.
So we actually had to cancel a wonderful conference that I was organising on the upside.
We started attending more online conferences and given little talks remotely to places in the US or elsewhere in Europe.
And without having to travel with so clearly as positive affecting, including the fact that there has negligible carbon footprint.
This is one of this positive things that is coming out of the pandemic.
And hopefully we will maintain the positive aspects and then go back to normal, having learnt some lessons along the way.
Another lesson that we we have learnt, and that's something that I think has changed that during the pandemic,
is that we see more international collaboration.
People are just more willing to work, try to solve challenges that the pandemic has thrown in front of us.
Also, we get a lot more attention from the press and the public,
and we do the best we can in order to describe our work and to keep the public informed to the best of our knowledge.
Your lab developed a rapid reverse test. Can you describe it and can you explain how it came to develop it?
Yes, we have been working, as I mentioned earlier on, the replication mechanism.
So for the influenza virus. So Saturdays work back in 2012 and more recently, we have been lowering ways to detect the flu virus more rapidly.
In fact, in November 2019, just a few months before we learnt about the emergence of the new coronavirus.
We had published a paper that was describing a method that was using calcium ions to bind tiny fragments or
fluoresce and DNA on the particles of the flu virus and other envelope virus and to label them for recently very,
very rapidly. So essentially you mix than flowers and DNA and calcium with the viral particles and they become almost instantly forests.
And then you can detect them on fluorescence microscope.
And by looking at the motion in solution or looking at their structure while they mobilise them on the surface,
you get information that may allow you to identify the virus.
So the timescales for labelling and imaging are basically just one to two minutes.
So it is very rapid. So when the coronavirus emerged in China, we thought that our AC will work quite well.
So with a new coronavirus and we had already some very exciting data on using images of the flu virus,
along with the use of machine learning in order to identify different strains of flu virus.
That was work that was done by a brilliant graduate student, Physick Senecal associate this in collaboration with a Royal Society fellow doctor.
And we called Rob, who now is an assistant professor at work. And that gave us a lot of confidence that this this methodology will work.
Also on the new coronavirus, so the important thing then was to be able to get the right samples in order to test the principle that
post on using a coronavirus from from chickens that showed that this principle is valid for coronaviruses.
And then in collaboration with an institute in Montpellier who had access to the new coronavirus and high containment facilities and microscopy,
we showed that indeed our idea was correct and the method was working quite well in terms of the detection, at least on the new coronavirus.
So what we did after that was to start working with colleagues in the hospitals on Rapid Fire Hospital,
which expanded on the collaboration we had started on bacterial targets in,
say, a few things a bit later about that that allows us to basically access locally
to the virus and provided us with space where we could install the microscope.
That allowed us to look at clean clinical symbols when we did this.
We managed to show that, again, the principle works not only on lab grown coronaviruses, but also on clinical samples.
So we have excellent accuracy when we look at individual particles of coronaviruses in clinical samples.
And now what we're doing is to be able to analyse many,
many clinical samples in order to establish the formal specificity and sensitivity of the assay and find ways
to make it also more adaptable and more high throughput in order to be able to be used for mass testing.
And the important feature of the methodology is its its speed.
Essentially, it wanted two minutes. You can have a result that identifies whether somebody has the novel coronavirus or not.
And it said and I say that this also quiet general and may be used for other viruses as well.
So we feel that this will have a substantial impact in terms of detecting dangerous viruses.
We'll see how much of an impact we'll have during this pandemic. But in any case, viruses will always be a some some visits and we should be prepared.
And it will help with that. You said that this work is involve collaboration.
Of course, the university Oxford. Way beyond the interest book.
And you say some more about this. Sure.
So the collaboration with the John Radcliffe Hospital and especially the lab of Derek Krook, I think both on called Stresser,
Monique Anderson and Lee and Teto was very, very important without them would have been able to show the proof of concept with clinical samples.
And we are extremely thankful for their support and their enthusiasm.
Also, I should point out the help from the Micron imaging you needs that is based in biochemistry.
Ellen Davis is a person who was heading this activity,
who actually support us by lending us a microscope that we could using in the short term for for about a month.
And that's clearly accelerate our timescale.
So that was an important contribution, our colleagues at Montpellier who actually contacted us after that.
So some of our efforts discussed the on on Twitter and then offered their help.
I was actually very heartwarming to see. And also colleagues per bright institute that studies animal viruses helped us in this effort.
And also,
I should say that there was support and various levels through our colleagues who are participating in the University Wide Calvet update group.
So it's other groups that have been doing Colvard related research since essentially meet the
January that the set of colleagues involves people who are working on developing the vaccine.
So the head of the Oxford Vaccine Group and my colleague Andy Poulard and colleagues who work on structural biology,
on immune responses, on track and trace. So we had excellent discussions there that helped us shape our project as well.
So this is a list of individuals and institutions that were very helpful in our efforts agency currently working well.
We are continuing our efforts on rapid coronavirus testing, but we have started our noncurrent virus experimental working in late July.
So on that frome's. We are finishing some very exciting work on the recent discovery of the detail mechanism by which the RNA polymers.
So the machine that copies DNA to do RNA. So. At the heart of gene expression, and we've done this for the machinery of the bacteria.
And then we understood the series of motion motions that take place in order to open their DNA to start the copying of the gene.
So very exciting. And we are wrapping it up for publication. We are also continuing the work to study the function of this chinnery,
along with the injury repair machinery by watching motions of single molecules inside living bacterial cells.
So that's ongoing work things.
It's a very good stage. And then another project that we're ramping up right now has to do with the rapid detection
of antibiotic resistance in pathogenic bacteria that are found in clinical samples.
And this sexually with the same team that we developed the rapid test for for coronavirus.
This particular detection has to do with bacteria, relies on single cell imaging and also involves advanced image analysis.
That includes also the machine learning aspect of the use of artificial intelligence.
The idea here is to be able to take a clinical specimen and to either analyse it directly or through
some minimal purification and then using imaging of individual cells as they are exposed different.
The biotics to be able to tell whether these cells are antibiotic resistant or not
and also get some information about what type of bacteria we have in the sample.
So that's a collaboration, again, with the colleagues in the John Radcliffe Hospital and also a colleague in their locker at the Big Data Institute.
And has this work has received a generous support by the Oxford Martin School.
So the project is starting basically in a few weeks.
The funded project. But we have exciting preliminary data already.
And another front of these quite important is the establishment of a new
interdisciplinary institutes at Oxford that will open in a matter of a few months.
And this is an institute is recently received support by the Kavli Foundation.
And this institute is focussing on using physical approaches in order to study biological mechanisms in living cells.
So we will actually be moving to a building has been completed obsessively.
Yes. As we speak. And therefore, will house many scientists that are working on on the physical approaches to deciding biological mechanisms.
Presumably, a new interdisciplinary institute is going to be taking your research into the future.
Could you say it's a bit more about that? Yes, absolutely. As I mentioned then, as you can see from the work that we discuss,
are the rapid detection of pathogenic bacteria, rapid addiction or coronavirus and other viruses.
We are doing more translational work than in the past because we feel that it's important to make put
our methodologies and competences towards a more immediate impact for the society and public health.
So we'd really like to make a contribution and to focus our efforts in the
method development or putting our better mechanistic understanding to words,
helping rapid detection and therefore helping the clinicians to to ensure better public health.
Also, I see that we will be doing more computational and image analysis work in the future because it's now in many of our projects,
extremely easy to collect. A very large number of data and images.
So it is to take. We have even commercialised microscopes that make this process of data acquisition quite, quite easy.
And there are more tools to do image analysis and data analysis and therefore provide
information that allow us to drive new experiments or new interpretations of existing data.
It's also something that can be done from from Holeman, as we don't know when exactly the end of the pandemic will will be.
Nobody knows the ability to do quite a bit of work from from home without requiring extensive experiments is quite attractive.
Also, I see ourselves doing more working in living cells versus doing work and purifying systems because they're more
biologically relevant and involve all the components associated with the growth and the maintenance of a of an organism,
sir. And the last thing I see that is emerging is that we will be involved in more collaborative efforts either internally within the new institutes,
but also internationally. And one of the reasons for this is that the problems that we're trying to.
Face are quite difficult that require a multidisciplinary approach.
And despite our lab being fairly multidisciplinary,
clearly will be more more effective and efficient if we tackle it with with colleagues and experts in in fields that we perhaps novices.
And the fact that we will have a new institute that will have this wonderful environment of groups
working on different approaches will make this more more easy to achieve and more enjoyable.
Really pillages. Thank you so much for taking the time to talk today.