The 2024 Ferrier Public Lecture presented by Professor Robert Field, director of the Manchester Institute of Biotechnology and Professor of Chemistry at the University of Manchester, was an inspiring exhibition of innovative science by a renowned carbohydrate chemist with a flair for science communication and application.
Good evening everyone and a very warm welcome to this evening’s event the annual faer public lecture um I’m Professor Margaret Highland I’m the deputy Vice Chancellor for research at the heading aoka Victoria University of Wellington um so distinguished guests um we have our our speaker uh Professor
Field we’ve got members of the faer family here colleagues Friends of the University Welcome to the university and welcome to this lecture um this lecture is present presented in honor of the late professor Robin frier who pioneered car carbohydrate chemistry in both New Zealand and globally today tea Udu faer Research
Institute is has an established reputation in carbohydrate and organic chemistry and staff from the in Institute are connected across various National and international Partners undertaking pioneering research that enables them to make an impact with science and I think that’s really important it’s about the science but it’s about the good that the science
Does um and it is indeed benefiting that joining us uh or befitting that joining us today maybe benefiting too uh that joining us today for the annual faer lecture is The Honorable Judith Collins the minister of science Innovation and Technologies uh with her remark able and extensive career Minister Collins needs no
Introduction um besides holding the science Innovation and techn Technology portfolio she holds seven other portfolios um attorney general Minister of Defense Minister for digitizing government Minister responsible for the gcsb minister responsible for the nzis minister for space lead coordination Minister for the government’s response to the RO commission’s report into the terrorist
Attack in the Christ Church of mosques so quite an impressive list and um while science Innovation and Technology may not be your largest portfolio Minister I’m sure you’ll find that it’s going to be the one that brings you the most Joy the most excitement uh and the most
Satisfaction I’m a little biased um Min Collins is the MP for papakura and she was first elected to Parliament to represent the seat of Cleveland in 2002 she holds a bachelor of laws master of laws with honors and a master of Taxation studies from the University of
Ockland and it’s wonderful to have you join us uh today Minister and I invite you to say a few [Applause] words well tin and good evening everybody it is my pleasure to be here at tonight’s lecture in honor of the late professor Robin FY and I would like to acknowled
Acknowledge Mrs Mary Goodwin and Dr Susan aan who have organized the events um Mr Jack hicker son uh grandson of Robin F fuia uh Mr John Allen Chancellor and Professor Margaret Highland Deputy Vice Chancellor of research before we hear from Professor field I’d like to say a few words on how
The government is reforming our Gene technology rules to support our scientists Gene Technologies are driven have driven enormous benefits for New Zealand from making advances in health science and helping combat climate change to lifting agricultural productivity and boosting exports but I’m sure that many of you have also felt
Frustrated at how our outdated Gene technology legislation has held you back under our current legislation the Environmental Protection agent has approved fewer than 10 GE or GM products for release outside Labs no commercial GE or GM crops have grown in New Zealand and no fresh fresh produce based on Gene Technologies are
Sold here countries like Australia Japan and the UK have safely embraced Gene technology and the EU is working to liberalize its rules we are being Left Behind putting our climate goals at risk and depriving kiwis of significant advances in health care Environmental Protection and economic growth so what we’re doing the
Government will reform New Zealand’s Gene technology rules so that we can give our scientists the tools that they are calling for we will ensure that they are Empower to do their research here instead of hurting them off overseas uh for trials and field testing we are
Working at PACE to enable greater use of Gene Technologies while ensuring strong protections for human health and the environment and the new rules will be future focused and designed to accommodate advances in gene Technologies and methods they will be based on managing the risks of these Technologies rather
Than focusing solely solely on the methods of genetic modification like Australia we will introduce a dedicated Gene technology regulator to manage risks so that we can take advantage of the many opportunities that Gene Technologies offer the regulator will oversee the new system it will involve a streamlined approval process to reduce
The burden on our scientists and businesses and help them to navigate the approvals process so that they do not get lost in confusing bureaucracy and I’d like to close off by saying this government is committed to getting the most out of New Zealand’s world leading science Innovation
Capability I want to enable the science Innovation and technology system to truly play a role and shaping the prosperous future of new for New Zealand just as it always his this government is committed to reducing the red tape that are slowing down progress and ensure the best
Settings are in place to turn research Excellence into Global impact thank you for having me uh here tonight and I’m looking forward to hearing from Professor field thank you very [Applause] much thank you Minister for your for your words and for taking the time to come um along to the lecture today I
Know it is a sign of the enthusiasm which with youold this portfolio have heard you talk about that and we look forward to working with you to ensure the future of a strong and effective research system um I now pass over to Professor Gary Evans who’s the director of the fair research
To introduce our speaker uh K thanks Margaret um I’m Gary U it’s great to be here tonight it’s great to be able to introduce Professor Rob field Minister that was really really interesting as a we we started off as a carbohydrate chemistry team and we’ve very much moved into the
Biotechnology space with our researchers like Parker and others uh doing an awful lot in the G modification space u all contained honestly so it’s all good stuff but yeah it’ll be interesting to see how we can roll some of those te Technologies out into the the field so
We’re very excited about that I know Rob who’s here tonight is head of a biotechnology Institute in Manchester in the UK and he’s seen um at firsthand the changes to their regulations seen what’s happening in in Europe um now that back out of Europe um you know watching from
Afar but they’re also then back into arising Europe which is a large funer of Science and seeing how some of those other countries are are treating their regulations so um it’s just a real pleasure to have Rob here he uh I first met Rob in 1991 which is uh aging both
Of us but he started off at uh the University of East Anglia in Norwich where he did his degree and then studied uh with alen Haynes for his PhD he then uh left there and went to uh the university Ox where he worked in the penan biotechnology team run by S Jack
Borwin Professor s Jack borwin better get that one right he was a formidable guy and so he and Rob shared a lab together initially with uh another friend of mine Dr Greg Lynch who’s in the audience here somewhere and so um it’s just great for the three of us to
To get back together again uh we certainly uh had a few barbecues together in the backyard um at our place uh back in the day so it’s great to see him here he left um Oxford in about uh I think it was 91 and went up to uh
University of Dundee where he worked with uh another sir sir sir Prof sorry Professor Sir Michael Ferguson and uh Steve I think Professor Steve homans and so that was at dunde for a couple of years and adjacent to that if you’ve ever been to Dundee and I have on a warm uh
Summer’s evening on a hill at 12 degre CSUS a bit like Wellington to be quite honest 12 degrees Celsius in the middle of summer that’s where Rob took us to see the view and so adjacent to that is St Andrews and so Rob moved there into a
Faculty position and in 1999 became full Professor there he returned uh to his roots uh he’s a cornishman but his wife is from uh Norwich uh East Anglia at any rate he returned to the University of East Anglia and uh into a faculty position there and then into the John
Owners Center I was trying to explain to the minister what what what the John inness was but essentially it’s an independent Research Institute specializing in plant and microbial sciences and so uh Rob worked there for a number of years he founded a diag I’m probably getting this slightly out of
Order he founded his own uh Diagnostics company I se Diagnostics and uh then uh in uh 2019 uh became or moved to the University of Manchester maybe it was 2020 beginning of 2020 where Rob became the director of the Manchester Institute of biotechnology Mi I I hope that’s
Right so he has um very much been in that role now for through Co um three four years has seen the challenges he talked a little bit about how the University of Manchester are bouncing back in terms of their enrollments what they’re seeing in terms of overse students but we’re here tonight to
Listen to what he’s interested in I think he started off as a carbohyd chemist and carbohydrates and organic chemistry in general really give you that I don’t know fundamental understanding of what molecular Sciences are all about and how they work and and it really gives you a rational way to
Intervene and investigate and make change uh where appropriate and so he’s going to talk a bit about that tonight um I won’t chat anymore I’m just going to say Rob would you come up and please give your fa public [Applause] lecture Minister ladies and gentlemen good evening
Um it’s very great pleasure to be here um I’ve promised to come visit for 30 odd years um I’ve been waiting for southern hemisphere rugby to die off a little bit to find the right time to visit uh I’m not sure that’s going to
Come in my life time so I decided it was time to come and uh this is a fantastic opportunity for me to come and uh celebrate Robin’s career uh and all that he’s done for carbohydrate chemistry globally but also the profound impact he’s had here in New Zealand uh in
Particular what I’ll do is tell you a little bit about some work that that we’ve done um I guess like Robin I’ve meandered between carbohydrates polysaccharides metabolism and biology on one hand and synthetic chemistry on another and what you find over the years is that these things come in and out of
Phase so Robins early work um with Calvin back in the late 60s in metabolism and polysaccharides Calvin won the Nobel Prize I think in 1960 for chemistry Robin moved on then coming here into to New Zealand and developing a lot of synthetic chemistry but I’m sure the Fier Institute people uh and US
Globally with the needs for sustainability are going back to polysaccharides as feed stocks we’ve got to get rid of oil from our supply chains and find some other form of carbon and polysaccharides May well be one of the key answers so carbohydrate chemistry gives you a grounding that allows you to
Move across a wide range of topics and I shall indeed do that today but first of course it’s not about me um as with any academic our most important output is the people that we train doesn’t matter how many Publications you’ve got it’s the people you train which is your key output
Because they’re the drivers of the economy those are the people that go out and really sell science at all sorts of levels from high school through to other universities to Industry and Beyond and indeed to government I hope so a big thank you to all the people that have
Worked with me over the years um this is the team as it was in in Norwich um just before covid so um you can see on the far side here not sure I can get the pointer up here but I’ll worry about uh David Russell my co conspirator
In this an analytical chemist so this is his team my team academically and then our joint team at iini Diagnostics um you’ll see where iini comes in along the way and and just for reference here you’ll see at the at the top some of the acknowledgements the bbsc the government
Funding body has been Central to funding some of the work that I’ve talked about uh they didn’t know they’d funded it until we’d done it um and that’s the way of Academia I’m afraid sorry Minister that’s just life um but but do note that we also got the environment agency the
Broads drainage board and the pike angling Club as funders of some of our research not easily achievable so I’ll come on to why and how that’s uh occurred as I work my way through so what I’m going to do is to tell you about two pieces of work which started off completely
Independently you get to a point in your career where you not necessarily motivated by another academic publication what you really want to do is actually make a difference and there’s nothing wrong with academic mic Publications but I think in the modern world that alone is probably not enough we need to be
Conscious of what we’re using public money for and where is the impact and some of that can be commercial and come some of it can be for societal good so two pieces of work one which was we think we know what we’re doing we’re building on many years of academic
Science both from ourselves and from others to try and take something in a commercial Direction and the second part of the talk is a Friday afternoon experiment we have no idea what the science basis of the program is we’ve no idea where it’s going to go hopefully I’ll convince you
That Serendipity and blue skies Discovery is equally important if you want to make an impact so we’ll see how that evolves so where to start okay yeah okay the human body is a lot of water and On A cellc Count basis what you see in front of you is less than 50% human
Cells right so the surface of the body the skin the lungs the gut are loaded with bacteria and fungi and viruses okay and this is really important because that’s a a mixed population which in a healthy individual is very very complex and it’s very easy to unbalance it now one of the key
Features in here is that the surface of all cells are coated in sugars so the first point of contact between a pathogen or a commensal microorganism in the human body is going to be sugar recognition so that gives us opportunities if we look at bacterial or viral infection First Steps binding of sugars
Very specific sugars on the animal animal or human surf cell surface if we can block those interactions we have a potential way of stopping infection an alternative to antibiotics in the case of bacteria for instance alternatively we can take these sugars and use them as a means of detecting bacteria or
Viruses so sugars present some interesting opportunities for diagnosis and therapy that have been underexplored over over the years sugars have impact in a much broader sense as well so on the left here you can see the turquoise structure is actually the spike protein from Corona virus covid-19 okay and that’s
What most biologists will tell you it looks like on the right hand side you can see it lagged in this blue stuff the dark blue stuff that’s sugar okay so why is it difficult to get a diagnostic a robust diagnostic why is it difficult to get a robust vaccine
Against covid the problem here is that the vaccine and the diagnostic need to recognize the protein but there’s not much of it actually exposed and it doesn’t take many mutations before your antibody based diagnostic is not going to work your vaccine is not going to work so carbohy rates are
Important and if you ignore them you end up with a very very stilted view of biology okay so DNA codes for RNA codes for protein and that’s the central Paradigm on which biology is based doesn’t tell you anything about the sugars ignore them at your peril huge opportunities for biotechnology to
Intervene now where is that intervention going to be be useful let’s have a look at influenza so influenza is one of those where we have issues in the human population it’s still a major killer globally on an annual basis and we also have Aven influenza which sweeps through both farmed poultry
Populations but also wild birds as well and causes Havoc if we take a step back over a century to 1918 and the Spanish flu virus that originated in Birds mutated so that it could jump into humans so it’s very risky to differentiate between medicine and agriculture when it comes to infectious
Diseases because one or two mutations can cause a crossover between species so one of the things we were challeng challenge to do was to come up with a way of detecting and differentiating between human and Aven influenza now the infection process for influenza involves two key proteins on the surface of the
Virus you’ll have seen things like this H3N2 is a human virus h5n1 is an Aven virus the H is a hemog glutenin so this is just a binding molecule that allows the virus to bind to the sugars on the surface of the lungs for instance the N is a neuraminidase and
This is actually capable of cleaving those sugars so what happens in the infection event is the virus binds to a particular sugar called cyc acid which I’ll come to in a moment that binding event allows the virus to get inside the cell it hijacks the host cell Machinery
In order to replicate but it can’t then Escape because it’s still bound to Sugar the neuraminidase Clips in takes off the sugars and the daughter viruses are released so the neuraminidase is a target for Tamiflu it’s an amavir alel Tamir the commercial antiviral drugs so those drugs are interesting they don’t
Block infection they don’t block replication they block the release of the replicated virus that blocking event the virus is held on to long enough the immune system kicks in and destroys the virus human influenza Aven influenza they both bind this particular sugar unit here called cyc acid but in a slightly different
Configuration so compositionally these are the same it’s just an isomer and the difference between the two isomers is enough to differentiate between a human virus and an Aven virus and that reflects what is prevalent on the tissues in human lungs and the respiratory pathway compared to birds so can we make
Use of this information to develop a diagnostic I want go through the fine detail here um what we’ve done is to take this particular sugar for the that the a the human virus binds to we’ve cuffed it onto gold nanoparticles now gold nanoparticles sounds exotic this is dirt
Cheap gold chloride reduced with citric acid lemon juice okay this has been done you can find these nanoparticles in stained glass windows going back 8 9 10 centuries it’s not rocket science so nanotchnology has been around a lot longer than people appreciate okay so gold nanop particles of a particular size are bright
Red and what we can show is that with these particles decorated in our sugar we’ve made these trimic versions because the protein the hemog gluten trimeric so we’re trying to get three points of contact at once if we have this suspension of red gold nanoparticles with the sugar on no
Virus is red if we put in the human Aven sorry the human virus the particles come together the photophysics changes and you get a color change if we add the Aven virus nothing happens because it doesn’t recognize the sugar so we can detect and differentiate human Aven influenza with a relatively simp Le
System now this is a 3 cm high glass tube that goes into £50,000 worth of spectrometer that sits on a bench not much use for practical use now three or four years ago I would have at this point had to introduce you to a lateral flow test and what that is
Uh we’ll forgo that one these days right so the bottom line is these gold nanoparticles are exactly what you use in elateral flow test it’s just that we’re putting sugars on them rather than antibodies and what you can see here uh before anybody calls me out on this one
The these are not to scale we don’t have abnormally big chickens in the UK all right so if we set up a device with the human sugar sequence on we can detect the human virus but not the Aven virus if we do it the other way around we can
Detect the Aven virus or not the human virus and the direct to travel is to have a control line a test line for human virus and a test line for Aven virus okay and the human virus should only light up one test line and the Aven
Virus only lights up the other one and if you’re unfortunate enough to have an infection that lights up both you know you’ve got the risk of a virus that’s jumping species and that’s when you need to panic okay so this is like any lateral flow test something you can do at home
And get early warning it’s something that a farmer could use in the yard okay you don’t need to take anything off the farm to get an answer out of this it’s very very simple all right so brand it all works clearly we’re going to make a
Fortune and probably if I made a fortune I perhaps wouldn’t be standing here telling you this so what is what is the challenge where where is the the downside here all right so diagnostics for human influenza one and a half billion a year Market it’s heavily regulated as all human
Diagnostics are it’s a global market and there are a lot of big players in it so we’ just set up by sen Diagnostics to try and translate some of this work about 10 years ago now barrier to entry into human Diagnostics is huge what about Aven influenza well actually the
Market’s much smaller one of the reasons for that is the uh the the department of U fisheries and food in the UK they have what’s described as a scorched Earth policy if there’s any notion that the farm has Aven influenza they literally take the map put a pin in it draw a 3
Kilm radius and annihilate all farmed birds in that region you ain’t going to make any money out of Diagnostics in that scenario right so the big problem for us in the UK is in fact not the commercial poultry producers it’s bird travel across the channel from Europe bringing things with
Them and we have a lot of hobby farmers in the UK have half a dozen chickens in their backyard that is the problem with Aven influenza that is the biggest undermining factor for the poultry industry in the UK okay so it’s not always what you expect but clearly this is a market
Where there may be scope in in Asia where there’s a much higher ratio of uh poultry to uh humans but for a small company in the UK to engage with China is hard one thing we do have in the UK is a substantial race Force industry through
New Market and a blood stock industry to go with it and horses also suffer from flu U maybe if you have a horse you knew that I had didn’t have a clue to be honest uh there’s an Emerging Market here for Diagnostics it’s rather unregulated in the vet sector and the
Barrier to entry is relatively low so we set out to do something for human health and we’ve ended up in a situation where our route to Market will ultimately support the horse racing and betting industry so you start out with the best of intentions and the science works but
You don’t know where it’s going to take you so we progress we’re looking to beta test back in March 2000 everything’s in place tests work they’re all packaged up and ready to go we have patents in place internationally and then in swep covid all right so as a small company at
That point we’re in a situation in the UK where everybody is being told shut down your workplace unless you are directly supporting human health yes you can furly use staff but when you got a limited amount of money in the bank you’re going to go bankrupt by doing
That so we had a number of options one was F the company and the other was to figure out how we could get back into a medical market so the obvious question is well what is the situation with covid which of course also has to infect and
How similar or different is it to influenza in the UK we’ve experienced more than 180,000 deaths from covid cases are way way in excess of 100 million which means that diagnostic tests run at probably approaching a billion test tests now I would say massive numbers huge opportunity will our sugar based tests
Work with covid so can we take what we’ve done with influenza and simply pivot it towards Co instead does it recognize similar or different sugars are we going to get any further in the human Market under a pandemic situation where there’s a dire need for
Impact so we were in in fact the first lab to show that the covid-19 spike protein is in fact a cyc acid binder and importantly the sugar it binds is just a single sugar unit of cyc acid which is simpler than the ligan for influenza so from a cost of goods a manufacturing
Perspective this is really important because it becomes Dirt Cheap so the ligans you need to detect covid is in fact related to zamir so produced by biotechnology at tons scale so there isn’t a cost of goods issue here to go into this space and importantly the mutants the
Various mutants the many mutants of covid we’ve tested 789 now they all bind this sugar so we have a diagnostic test unlike the antibody based tests which don’t cross over between the mutants we have resilience built in here so the technology works but when you start to look at the real
Financial realities of the situation and you start dealing with regulatory processes and government procurement processes Things become a little sticky so if we look at the equin influenza Market a couple hundred thousand tests a year we can sell them for20 if we were selling them to private
Individuals they’d pay an awful lot more than2 because they’re worried about the their horse having the sniffles right in contrast the government will only pay 2250 for a test for you okay so 200,000 tests a year for Ean influenza we can legitimately make around about 2.8 million profit of that
To make the same level of profit off a covid test with government procured processes we need 5.6 million devices the government won’t even talk to us until we can produce 500,000 tests a day and they want that 5 days a week for three months before they will discuss contracts they will only discuss
Contracts if we’ve already secured our supply chain in other words paid for the process so we’re in a hole before we go anywhere here and quite a number of Diagnostics companies in the UK have in fact gone to the wall because even if they’ve got a govern government contract
The money hasn’t come through quick enough to bail them out so it’s been challenging dealing with diagnostics for infectious diseases in the UK to give them their credit the UK government has been spectacularly successful with procurement of mRNA vaccines for covid so they don’t always get it wrong but the disconnect between
Discovery Science push and Market pull and Regulatory Affairs is a challenge so the science works there’s no doubt there’s a need but we need to be more joined up at the regulatory level early and we need to understand where the government is coming from in its procurement processes much earlier in
The process so you can’t dis disconnect the early phase Discovery Science from that route to Market if you really are going to make an impact so there’s room for maneuver on both sides the academics need to step in One Direction and government needs to step back in the
Opposite direction so that the two will meet on a more regular basis I I trust that things are more joined up here than they are in the UK okay it’s difficult it’s difficult now we don’t all spend our time at work seven days a week right we have a life to live as
Well so what else goes on out there in the world so this is my long-term collaborator and good friend uh Martin resek as you can see here he’s a very keen angler and this is a piece of work that started in Norwich here in the east of
England so this is a very low-lying area most of this region is in fact below sea level and there are extensive waterways here that run to one or two met deep they’re in fact not natural water ways they’re the result of peak digging in the 11th and 12th century so
1 to 2 m deep extremely sensitive to changes in uh the weather on a hot dry summer the water levels drop further you can see this is very close to the Sea the North Sea so there’s a lot of salt incursion into these waterways they’re in fact brackish not um fresh
Water and the norfol broad says called make a massive impact on the local economy I can see some of you wondering what on Earth has this got to do with influenza bear with me I will join the loop here all right so very popular with the Anglers and of course there’s a big
Boating um industry holiday Cottages the works so tourism 500 million a year which 100 million is from angling so this is a this is a massive money spinner in the local region and on a good day you know this is absolutely beautiful you you need to be careful
About where you’re swimming or where your small dog is swimming clearly with these beasts around on a bad day it doesn’t look so good okay so there’s reports going back over A Century of periodic algal blooms and they turn the water this golden color and you end up with mass fish
Deaths now I knew nothing about this even though I’m a ke angler so my friend Martin comes in to work on a Monday morning oh I was out fishing at the weekend there were dead fish everywhere the Anglers were up in arms um Martin made the big mistake I
Guess of telling them he was a scientist and the response of course is well you’re a scientist you must be able to do something about this so he says to me what are we going to do about it I really haven’t got a clue uh I don’t
Really know anything about algae and I have no idea what toxins they produce and at the time I’m working in a plant Sciences Institute and we can get away with starch and we can get away with cell walls but there’s no carbohydrate angle here so how on Earth am I going to
Justify this to my line manager my head of Institute now as it turns out this particular algae golden algae primium par it’s a marine organism so you wouldn’t expect to see it outside of the oceans but it does come into the brackish Waters in The broads it is in
Fact a global problem it’s a major issue for fish farming in Texas and across China um there was a major incident in Poland in 2022 hundreds of tons of fish killed now this is several hundred miles from the Baltic okay it was the hottest summer on record and the lowest River levels on
Record so the water isn’t there but the salts running off from agriculture land are so algal blooms are often associated with high nitrate High phosphate typical fertilizers when you’ve got low Rivers you’re in trouble and that’s exactly what happened here in Poland in 2022 so major issues there’s a need for early warning
About blooms there’s a need to understand what the toxin is and what on Earth is going on here and how to do something about it now the current mitigation strategy from the environment agency in the UK is we’ve got fish that are not looking very
Happy we’ll put a net in the water or’ll take him out of the water and put him in a tank on a truck drive it down the road and then put them back in the water again that’s not funny when you’re dealing with several million fish and of
Course you don’t know whether you’ve exported the problem with you in doing this or whether you’ve actually moved the fish somewhere where there’s a bigger problem than where you started because you’ve no idea what you’re doing what are the molecules where is the science problem the Anglers were so excited that
We were doing something they went straight to the papers and told them that we’d got a solution uh we hadn’t actually done anything at this point so no pressure need to do something quick and it needs to be obvious and straightforward right and this is Toxin so for the
Chemist in the audience you’ll realize what a beast that is okay for those of you who are not chemists the molecule in the middle here is around about the size of glucose or aspirin or caffeine typical bioactive molecules this is horrendous why a single celled organism would produce anything this complicated
It defeats me completely um as far as we know this molecule as is typical for these type of polyethers it’s an ion for it SE sticks in the Gill membrane it depolarizes the sodium potassium gradient and that blocks oxygen uptake so the fish essentially suffocate and you can see that while
Them rolling around on the surface of the water the yelds which are super sensitive to this toxin they’re smart they just get out of the water and go across land to get away from the toxin okay Beast of a molecule um how on Earth do I sell this to my head of Institute
Well at least there are some sugars in here I can might stret in the point a little bit but it it’s a bizarre natural product there’s lots of functionality in here which actually is really quite challenging quite interesting there’s some unusual sugars I won’t dwell on that um there are three chlorine atoms
In this molecule as well as the chyo polyether system up the middle there are double bonds and triple bonds including this terminal alkine which I should come back to in a moment so there’s a lot of functionality here which is either in contemporary drugs or it’s used as an
Intermediate in the production of contemporary drugs but nature makes these molecules in single cell organisms ambient temperature and pressure in water so we’d really love to know how nature does this okay because this is a tool kit that any synthetic medicinal chemist would love to have so I
Justified it on that basis and on we went mindful that we’ve got the Anglers over our shoulder we need to detect terminal alkine again that will come as no surprise to anyone with a chemical background in the audience that solution is therefore click chemistry so this aidoc cumarin is in fact not
Fluorescent but if you click it onto the terminal alkine with a little bit of copper one the resulting triol is th resent you can see that there were in fact a series of isomeric structures here when we roll this out on TLC so simple test we can confirm the
Presence of an alkine based natural product alkin are extremely un extremely un uh unusual in nature so we can pretty damn sure that if we’ve got any fluoresence coming up it’s going to be this toxin okay so very simple straightforward chemistry to do that things got a little tricky then
When we tried to isolate the algae from the water and grow them in the lab because they would grow fine for a few days you can see the red Trace here and you got a nice golden color and then overnight everything collapsed and everything went colorless and there was
There was some paranoia in the lab at the time that somebody was swapping distilled water in uh and playing tricks on us that turned out not to be the case in the end what we did is to take alal cultures at this stage when they’re starting to die and ask the question
Well what’s similar or different here so using electron microscopy we can look at the inner workings of the cell and look at all of the bits and pieces in there that are necessary for the normal life cycle of this this organism and we see the bits we expect the
Chloroplast vacu and nucleus the nuclear en uh envelope and scales on the surface of this particular organism so this is from the culture collection when we do the same then with the algae from the wild it looks it looks wild right there’s no nucleus in here it’s completely gone the mitochondria are
Manyfold and much much larger which is generally the sign of stress the giveaway is these icosahedral structures at the bottom now at the time I was sharing a lab with a virologist so it didn’t take as long to figure out that this might be virus but it had never occurred to me that
Viruses infect algae okay fair enough um naive chemists blundering around in biology well we’ll just isolate it and we’ll sequence its genome as she do gly say these days so we did even though we were told it was really not going to be doable so what I’ve done here is just to
Map up viruses for you Rhino virus which causes common cold HIV flu and Ebola so you can see from the physical size here they vary quite a lot and then the bars here only one big bar is the size of the genome the am essentially the amount of DNA the number
Of genes in these organisms so very very little in the virus because the virus is really infecting and hijacking the host Machinery it doesn’t need much it’s lean and mean it’s not living it can’t reproduce independently until we get to the pesum virus which has an absolutely enormous
Genome it has lots and lots of DNA in it um so the more we dig the more complicated it becomes lots of DNA what does it look like so it appears that while influenza HIV and so on produce about half a dozen different proteins or thereabouts this virus produces 3 32
Proteins so that’s more than some small bacteria which are independent living species right half of those genes encode for proteins that don’t look like anything in any other organism known to man so there’s a whole raft of biology here that we know nothing about there’s nearly 80 proteins
Involved in DNA biochemistry so that’s normally replication the root to living a virus that’s got nearly all the Machinery it needs to replicate independently disturbing focusing on what I might know a little bit about carbohydrate biology we can find 14 genes associated with carbohydrate biology I’m not going to go
Through all the detail but what came out was uh a sequence that’s apparently a hemog glutamin and another that’s a neuraminidase paranoia kicks in again somebody’s contaminated the samples with flu no this is genuine so we’ve in fact gone on to demonstrate that we don’t have a hemog glutenin that
Recognizes the sugar that influenza recognizes but it does recognize one very similar so there’s rather subtle difference replacing an acetamide with an alcohol we’ve demonstrated that the algae can produce this sugar and attach it to their cell surface so it looks as though what we’ve got here is potentially
A life cycle going on in the water which mimics what goes on in your lungs with influenza completely different classes of biology but common mechanisms of replication and Escape so what we think happens then the Ali probably are not that toxic they produce toxin but they don’t release it when they’re infected with
Virus if the cell count of the algae goes up it depletes the nutrients in the water column and you can see that by a dropping the oxygen partial pressure and an increas in the pH that stresses the algae the virus inside senses that stress and thinks right it’s time to replicate and get
Out and in so doing it lies the algae and liberates the toxin so the AL per se are not a problem they’re not going to produce enough toxin regularly enough to cause the fish kills it’s The Coincidence of the algae and the virus that’s the problem so we’ve Now set up
PCR tests that detect both the algae and the virus and that’s the positive for you’ve got a problem so we’ve got the Diagnostics in place we’ve Rewritten essentially the textbook for what happens in an alol Bloom and the releasee of toxin so we’re feeling really quite pleased with ourselves at this point chemists
Meandering through biology and doing things biologist wouldn’t do when coming up with really unexpected discoveries but you always have to be careful when you’re dealing with your stakeholders because their perception of impact and importance is very different so rooted Again by the expectations of the angling Community what are you going
To do about our dead and dying fish we’re not really bothered whether there’s a virus there or not what are you going to do about dead fish all right now we’re working in a national park we can’t just throw algicide around we would not get approval to do
That so we’ve got to come up with a smart solution which is simple and compatible with the real world so one thing we’ve reasoned is that the Water waste often have very low oxygen levels and the way that’s dealt with is not to pump in oxygen the environment agency pump in
Hydrogen peroxide which is a reagent that many in the audience will have experience of it’s a strong oxidizing agent and I’ll come to that in a moment but in the environment particularly in the presence of iron salts rust and the like it breaks down to water and oxygen so it’s
Essentially traceless at the end of the day it can do some damage but then it disappears on you which is exactly what we need if we’re going to do this in a national park right now hydrogen peroxide some of you will have come across in a different sense 7% hydrogen peroxide is hair
Bleach 3% hydrogen peroxide is teeth whitener you can actually get 3% hydrogen peroxide on Amazon as food grade I’m not sure I’d want to drink it but um so be careful when you whiten your teeth the the environment agency already have the infrastructure to use peroxide in the environment to aate the
Water so we’ve worked with them to Simply dial up the concentration of peroxide they’re using so that there’s a bit more front end damage being caused to kill the Aly so they have all the infrastructure the technology is dirt cheap next set of field Group experiments are out in the wild um
Signage on the roadway keep path chemical dosing in process so we’re no longer in a test tube we’re now in several kilometers of Waterway for our reaction vessel okay 50 gallon drums of peroxide and health and safety for that of course means face masks and full
Suits you can see one of my team here looking rather amused at this this is teeth whitener but this is hazardous material right as far as the Public’s concern here you can see it being bubbled in the water and what we’ve shown with this approach is that we can
Take out the bloom and as from a chemistry perspective anything with alenes and alkes in it you’re putting hydrogen peroxide in there you’re going to get rid of the toxin very quickly as well so we can take out not only the algae but also the toxin with the peroxide and peroxide infrastructure
That the environment agency would normally use to aate the Waterway it works nonetheless we have to demonstrate that we’re not doing any lasting damage so we’ve had to turn ecologists and count the fish and count the insects um the scum on the water here you can see when you when you take out
An alal Bloom you’ve got a lot of lized algal cells the lipid membranes form a little bit of an emultion on the surface absolutely normal no big deal the biggest problem we had was not the insects nor the fish it was in fact the boats right so this boat was white when
We started I must say that so we had to prove to the broads Authority and to the Boatyard owners that putting hydrogen peroxide into the water would not leech the boats so literally plank of wood red paint bucket of peroxide I really struggled to get the director of plant Sciences Institute to
Pay for that so there are some in the community who were really not worried about the Ecology of the Waterway they really were only worried about the boats nonetheless no damage done all sorted so this is one of those pieces of science where it all worked out there is
A societal need and a benefit to be had we have Rewritten the policy and practice with the environment agency it’s changed their protocols so at a at a a cerebral level if you will we’ve changed thinking about what actually goes on in the Ecology of this system
But at a practical level we’ve also got very simple chemistry that can be rolled out on a field basis the Anglers are happy tourist Border happy job done okay so that all works so this is quite the antithesis of what I started out with where there’s lots of B
Basic science and we’re trying to take it through the Commerce that’s hard here we had no clue where we were going but we’ve still come up with a practical solution as well as a lot of Discovery Science so I think it’s really important that we think about that interplay between
Discovery development and application because Innovation is needed in all areas a lot of Discovery Science is very difficult to predict where you’re going there is a level of serendipity and my God we need to support that because the applications of 20 years time will be based on the blue sky discovery of
Today and this is a cycle once you’ve gone from Discovery through development to application you identify where the shortcomings are and then you need to go back to Discovery but you’re not going to turn that Circle Without Really rooting it in engagement with policy and Regulatory approval early so I think
It’s important that from an academic perspective we think about how are we going to achieve impact and what are the hurdles in the way and the hurdle is generally not the science and most scientists rarely take the steps that will force that issue for them equally it’s important for government and I’ll
Say this for UK government it’s important to fund Discovery Science and not just application because as I’ve already said the discovery of today is the application of 20 years time and it would be full Hardy to walk away from that and think that you can manage everything through application
So a little bit of science a little bit of societal benefit a little bit of Commerce um we’ve had some fun along the way hopefully I’ve kept you entertained for a little while I’d be very happy to take any questions and thank thank you very much for
Listening cool um that was great thanks Rob I I want to know where you would be if you’d made your bonss if you weren’t going to be here Rob if you w going to be sat here or stood here where would you be angling somewhere yes Cho maybe
Um okay we’ve got time for some questions um Anette and Lawrence have uh microphones if anybody would like to ask a question please raise your hand and they will come to you come on someone must have a question the back up the back here we go thank you that’s a simple question you
Consider Theus we’ve looked longingly at the Middle East because of the value of their Falcons yeah no no word of a lie on that one you’re talking about tens hundreds of thousands of pounds for a flying falcon in the Middle East um we’ve also started to think about the British royal
Family who like to take their horses onto the race course right and the police who do likewise um we’re also talking to the Jockey Club in uh Hong Kong and also in Kentucky so there are Global opportunities but you have to spend a lot of time on the road to hit all of
These uh opportunities there are many and varied for sure another one up there oh there’s one sorry I’ll bear that one in mind I’ll bear that one in mind all oh k um thanks Rob for a great lecture I really love that kind of combination of the Blue Sky
Science the you know go to the people who are having the problem I love that you know the angle is kind of going back to you and going great but what are you going to do about it and I think that’s so important to engage with that and actually makes our science better
Because it forces us to think differently so I love that feedback loop um the only thing I was going to ask about you know in terms of your you identified the regulator and the government um I’m an engineer and so I also think about scale up yeah so do you
Have any comments about how you engage in terms of actually getting it to the to the scale that you need and when does that occur absolutely that’s a critical one as well I think that that’s why I was so pleased that you know the molecule we needed for covid maps to a m
Amov which has already been industrialized from a biotechnology perspective one of the major shortcomings still in the UK at the moment is scal up so there is a burgeoning biotech sector but taking things Beyond a couple of liters is hard and making sure that you’ve got that route from Discovery through to scale
Quickly is critical uh if you’re going to drive the economy with that in place we we see this a lot not so much in the in the Fine Chemicals and and medicines area we’re seeing it in the home care products so the unever and the proter
And gambl of this world they won’t come near us unless we can put you know on the table when we normally work with milligrams and there isn’t an easy way to go from where Academia sits to where the big companies sit that’s actually driving um the development of Ann sector
To serve as that intermediary but you need the infrastructure and it needs to be a national infrastructure not a local one because you need to you know this is expensive infrastructure you need to milk it for all its work so it needs to be coordinated on a national basis I say
Cool and I have a a question have you considered given that toxin is so unique and challenging structure and the virus that you have has an enormous number of genes unusual for that that in fact there some of those genes are enabling that production of that toxin within that particular
Microorganism that’s an interesting one um so we have started to look at the metabolite profiles in the algae after the virus is infected and we’ve just looked at Sugar nucleotides because we know how to do that they’re all over the place some sugar nucleotides go up by 50
Fold in concentration and we don’t really know why yet um so there’s definitely an impact of the virus on metabolism in general um in terms of whether it’s contributing to the production of the toxin um we don’t think so so there’s a paper just come out it’s actually not
Even out it’s on bioarchive at the moment from the scripts Institute of oceanography where they’ve discovered the enzyme the gene for the enzyme that makes that toxin it’s one protein and it’s in excess of of a mega dalan in size it’s bigger than any human protein so it’s got something like 65
Independent catalytic modules on one protein okay and we see this a lot in the algae whereas a back iium would have an operon and it would coexpress a number of genes what we see in the algae is that they’ve acquired these bacterial capabilities by horizontal transfer and
In the act of doing so they Stitch protein the the genes together into a single protein so Al like making polyproteins which makes you know you look at your SDS page gel and it doesn’t even get out of the stacking yet so it’s quite bizarre so yeah uh I’m going to
Have to find something easy to work on something any more questions for Rob we don’t know on that one one one of the problems in the algae is that there there are so few genome sequences that we’ve not were not able to track the genetic lineages back in time easily at
The moment um we’ve started to do it a little bit in relation to this this unusual sugar that’s the receptor for the virus so we can track that across different lineages of algae and it’s very very specific in some areas and ancient so the production of the algal
Sugar and the human sugar the animal sugar this is very very old biochemistry um and the Divergence between one and the other it goes back Millennia at least so there’s an awful lot more to come on that front yet to try and understand the the relationships between the various algae and and other
Organisms thank you um Robert um I have a question is about Alzheimer disease um is true lifestyle like cutting down alcohol having enough sleep to prevent or you come up with research for medicine to to prevent Alzheimer disease that’s a challenge um I think there are lots of new discoveries coming
Through all the time lots more information about structures of the proteins that cause the problem and mechanisms to remove those proteins a lot of those proteins are not degraded naturally by the human body which is where the problem comes from so as a therapeutic therapeutic approach in
General um there’s a lot of interest in the viruses that infect bacteria bacteria phages they produce a lot of degradative enzymes so there’s a lot of interest in phage therapies not so much in the Alzheimer’s area yet but certainly in relation to cancer and in relation to infectious diseases so just
To give you a flavor so the human gut has 10 times more viruses than it has bacteria okay you’ll have heard of Nora virus for instance but that’s just a drop in the ocean so viruses controlling bacterial populations is part of normal homeostasis so not all viruses are bad for
You and we’re now starting to get to the point where we can cultures viruses in vitro that have the necessary hydratic capabilities to do something therapeutically useful so that’s the next generation of therapies coming through I feel that um offers a lot of scope particularly in in a an
Antimicrobial resistance era where we need something other than just antibiotics last question thank um hi professor Robert so um it will be a very general question so um since last year like Nobel Prize was handed to um chemistry is kind of like related to quantum physics and um so
Like last year’s Nobel Prize was like chemistry and was like related to physics so um my question is like like this lecture is basically about like something that around virus andry actually applied Ino so what will be like the future about like the traditional um like all of these things
Are actually that related to yeah yeah abely at the end of the day on the right um and biot technology is fantastic and it offers huge opportunities and with all the genome sequencing programs we have loads of new tools loads of new opportunities but if you look at the
World’s top drugs they’ve got Florine in them nature doesn’t do flourine very well we’re never going to walk away from synthetic chemistry there will always be a role for it the power going forward is the integration of synthetic chemistry and synthetic biology to take you places that chemistry can’t take you and
Biology can’t take you but the two together is where the power comes for the future I’ve heard plenty about that today from the people here so I’m sure you’re all on the right track brilliant thank you Rob and uh just thank you everybody for coming along we really
Appreciate it hopefully you had a drink and a nibble and uh I just want to thank Rob one more time for coming all