Session 2 of Discovery Days 2024 features the following talks:
00:01:17 – 00:16:49 Dr David McBeth – The University as a driver for economic transformation
00:19:29 – 00:37:07 Professor Liz Miller – Policing secretion: How cells ensure accurate delivery of proteins
00:39:34 – 00:56:08 Professor Shawn Mu – What blows with the wind?
Discovery Days offer a fascinating exploration of a wide range of important topics, from health and wellbeing, human rights, and our ground-breaking scientific research and arts practice. All our speakers are helping us to transform lives locally and around the world.
https://www.dundee.ac.uk/engage/events/discovery-days
But three very different perspectives, two from newly appointed professors and one from a newly appointed member of our senior team, the university executive group, our new Vice Principal. So that’s what you’ve got in front of you for the next hour or so. The session lasts an hour and 15 minutes.
Each of our colleagues get 15 minutes, it says on my brief or so, So 15 minutes – the hook will come out and you’ll be pulled off the stage. Just 15 minutes to give you a sense of what they’re doing. And then once we’ve had the three presentations,
Colleagues will come up and join us here in a traditional panel, and it’ll be the opportunity for those in the room and those online to ask any questions and hopefully we’ll get a bit of a conversation going. And then we’ll stop in an hour and 15 minutes for another cup of coffee,
And then the next session will begin after that. But first of all, let’s enjoy ourselves. Please join me in welcoming the first of our speakers and Dr. David McBeth, who’s going to be talking about University as a driver for economic transformation. David. Well, thanks very much and welcome
To those of you that weren’t already here for the court session. As Ian says, I’m going to talk about the kind of portfolio that I have as a vice principal in the university enterprise and economic transformation. And I’ll try and give you a bit of a sense of the lens
That I look through when I look at that portfolio. So this slide, although it says, ‘What are we trying to achieve?’ I mean, it’s a kind of mixture of what and why. It’s not just what. I think we’re a big employer in the city,
Which is quite a mixed city in terms of its current economic status. You know, there’s poor areas in Dundee, a lot of deprivation. There are also better off areas and there are people in useful employment, but there are a lot of people who are unemployed or underemployed.
And the University is such a big actor in this city that I have, I feel, a duty to try to have a positive impact on our city. And although we’ve talked about economic transformation, I’m seeing that as economic health, wellbeing and social purpose. And that plays onto the right hand side of the
Diagram there, because as well as doing things that are positively beneficial to the city of Dundee and its citizens. The second goal, I think of the enterprise in economic transformation strategy, if you like, is to gain a reputation beyond Dundee for being good at this kind of stuff
And that is really important in a number of contexts. It’s particularly important in terms of convincing government and policymakers that this is a sensible place to invest in, but it’s also important in terms of setting up a university that’s seen as entrepreneurial, that will attract certain types of staff
Or attract certain types of students, and it’ll provide some competitive edge to the University of Dundee in the longer term. So it’s got that kind of immediate impact in the city and longer term reputational impact for the university wrapped up in the portfolio. There’s three
Ways in which I’m proposing that we’re going to achieve these things. The first one is institutional headway in initiatives. These are typically a big splash in some respects, typically a significant capital project. They’re big enough to be measured against their own business plans, which must pass muster
With the university executive group and with university court if required. But all of these should play, must play into the goals of the Schools and the University for its core activity so if they don’t benefit research or teaching or engagement, then we shouldn’t be doing them. So they have to be…
They have to meet that criterion. And what we’d say as well that they wouldn’t always involve every School. So, you know, some of them may be single school based initiatives, some of them may be multiple school based initiatives. They do need to enhance the academic
Endeavor, as well as having an impact on economic matters. Likewise, there will be school led engagement activities. We’re not starting from ground zero with this strategy. There’s lots and lots of good things going on at the moment. What I want us to do is for the university corporately to adopt one or two
Or maybe three of those initiatives that are already going on and give them a bit of power, give them a bit more university-wide endorsement that helps them to deliver (you know, the left hand side of that first slide that I put up) helps them to deliver an impact in the city.
And then the third part, which is kind of my historic bedrock, is professional services enabled enterprise activities. So that’s specifically assisting staff, students, alumni, friends to form and grow companies here that will employ people here and hopefully that will have a very positive direct impact on the city.
But they will be separate entities. We help them to form – the Research and Innovation Services, the University’s Centre for Entrepreneurship help things to form, help them to raise money and let them get out there and contribute to the economy of our city. I’m starting with the headline
Initiatives, and I’m kind of starting in the top left and going clockwise. The Life Sciences Innovation District is probably the most ambitious of the initiatives in which we are taking a leading position. And that’s the picture that you see there is the TechnoPol site,
Which is across all Hawkhill Road from the Life Sciences Building. Partners in the Life Sciences Innovation District proposition are Dundee City Council – I don’t know if anyone from the council is in the room, I hope someone will be on Teams – and also Scottish Enterprise are a partner in this.
The ambition here is to create a thriving research and development-intensive local economy for biomedical, life sciences and health-type companies. The goal is to have high hundreds / thousands of employees. in those types of companies in kind of 10 to 15 years type time. And that’s the vision that has been bought into
By those other partners, Dundee City Council and Scottish Enterprise. I think the other thing to say about that is it’s not all PhDs. If these companies are successful, there’s opportunities for employment to all levels, technician level, support staff level and hopefully a direct pass on to better prospects for people who are born
And brought up here in our city. Using the pointer of this here is the same thing as this, this is the Innovation Hub and this building is currently coming out the ground on the Technopol site, If you’ve been over there, you’ll see it. This is funded by
The Tay Cities Deal, which some of you may have heard of. It’s existed for a few years now. UK and Scottish Governments have committed to a program of total value of 700 million in the region and the intention is to do all sorts of different projects that will have a huge impact on
The economic prosperity of the Tay cities region. This is just one of those projects – the Tay Cities Deal is putting 20 million approximately into that building and the other 20 is a mixture of a significant commitment from the University itself, which is very much appreciated and shows
How committed the University is to this kind of stuff strategically and also from another public sector agency that I can’t quite name at the moment. But you can probably make an educated guess. The Innovation Hub will open at the end of 2024, and it will have a
Number of ten companies from day one that are in their early growth stage of their journey. And we hope to retain those companies for the benefit of the economy here. And there’s lots of people who deserve tons of credit for the work that’s been done in getting to this stage.
I won’t take time to give the namechecks because I’ve got one eye on the clock and I’m already slowing down. The third one here is the JustTech project. That’s the University’s other project under the Tay Cities Deal. This is about piloting new technologies for the justice system,
And it’s based on the excellent reputation of the Leverhulme Centre for Research and Forensic Science, which the University already has. And it again has got an economic impact. We very much hope that companies who have technologies that can be used in the justice system can come and locate to this hub.
And it should be opening – it should be getting built in 2025/26. And then the final one of these is the Eden Project. A lot of people will have heard of the Eden Project for Dundee. The proposal’s that there will be a significant development (I’ve gone two slides on, my apologies).
This is the kind of current gasworks down by the harbor and the proposal is that the Eden Project will be £130 million development there. Again, opening in 2026/27 if things go according to plan. All of these things are in scope for what I’ve been talking about, because they have the potential to be
Synergistic with the things that University wants to do anyway. They help us to demonstrate impact from our teaching, they help us to demonstrate impact from our research, and they also have a positive impact on the fabric of the city. And that’s why these headline initiatives are so important.
This is intended to be a generic member of university staff. It could be an academic, it could be a member of professional services asking, well, “is this relevant to me?” And I think that leads onto the to the school-based initiatives, which I mentioned
As the kind of middle panel of the of the things that I was talking about. And this is just intended to illustrate the point that I already made, really, which is that there are already a lot of things going on that have the potential
To be very beneficial within the city and for the city’s citizens. And that might be one or more of these that we can grab ahold of and really turbocharge and put our weight behind. So the ‘Drug Death Crisis’, that’s actually a student-wide initiative,
That student action has created it – some of you may already have had some exposure to that project. The ‘Urban Relief Project under Green Planning’ – that’s very much a kind of citizen-signed, citizen action project. It’s led out of the Duncan Johnson College of Arts and Design and it’s been funded by European
Funding historically. But it’s got a life of its own and it will continue beyond that funding and again, has an impact on the environment that we have here in the city. The ‘law clinic’ and other clinics – yet another really good example where the citizens of the city receive benefit from our students
And our students gain benefit from being involved in practical casework. And finally, the ‘Help to grow’ program, which is run out of the School of Business. This is a training course effectively for people who have started businesses. They don’t need to be technology businesses, they don’t need to be research based businesses.
They just need to be small businesses. And the business leaders get structured training free at the point of use to help them understand how to grow their businesses. These are just examples, but the purpose of them is to illustrate that one or two of these things or things like them,
We need to adopt them and really give them the absolute maximum fuel we can to make them have that impact on the city, which we can then use as a kind of beacon for other people to do the same sort of thing.
And moving on to the final part about the company creation stuff, the principle’s already touched on that and I’ve already touched on it. Creating companies is vitally important, I think, to a city like Dundee. And it’s important for the University as well.
But it’s most important for the city because the idea of forming new companies that can grow is vital in regenerating cities that perhaps got to the point that Dundee has got to where, you know, there isn’t as much employment here as there should be.
But there is a wealth of talent and a wealth of creativity, not just amongst the staff and students of the University, but amongst the people of the city. So as Iain mentioned, you know, we’re rated number one for spinout companies in the last year by Octopus Ventures.
But over the preceding two or three years, there’s been fourth, fifth and sixth. These are completely independent ratings and these are in the UK that’s first in the UK and fourth, fifth and sixth in the UK. It’s not usually first in Scotland.
So we’ve been externally recognized without having to ask for that recognition because we are doing a really good job in that respect. And I think it proves that with the right stuff and the right people and the right support, you know, there’s
A really good chance for Dundee to build a decent economy around about this. And these are some highlights of the University’s kind of current portfolio of companies that have been formed. Almost all of these are in the kind of biomedical health life sciences type area.
But I don’t want to pretend that those are the only types of companies that we form. And in fact, some people here may be familiar with the company STAR-Dundee, that was formed probably about 10 or 15 years ago. I’m acutely familiar with it because one of my colleagues from Research
And Innovation Services was poached by them in 2023. But it gives a good view that the company is making good progress. But these are some examples of these companies. Most universities in Scotland would be a jealous of us for the companies that we have in our portfolio.
Particularly jealous of the two that I’m going to touch on later at the end here. Exscientia, which I think a lot of you have probably already heard of, artificial intelligence enabled drug design and founded here in in 2012, I think by Professor Andrew Hopkins, who’s still the chief executive of the company. And
It’s already got 450 employees and as you see there, somewhere. Biggest European biotech IPO and in 2021 and you know at the point of its gestation as been valued at over 2 billion USD. Amphista, on a similar path, and much more about a particular therapeutic class, based very much on the technologies
And research of Professor Alessio Ciulli in the School of Life Sciences. Fantastic credit to these companies for the journey they’ve been on. But I think to kind of wrap around, to kind of conclude what I’m seeing both of these companies I know headquartered in England
And the majority of the staff of Exscientia are in England. all of the staff of Amphista are in England. So that’s not getting the University, that’s not giving the city of Dundee the economic benefit that we would like to give it. And that’s really the key reason for the proposition
Of the Life Sciences Innovation District and the Innovation Hub, which is the anchor to these companies – nearest to where they had formed, nearer to the talent that created them in the first place and deliver that economic benefit to the city. So that’s the flavour from me.
I know I’ve got a couple of minutes left . That’s the kind of length that I see things through. And not all of these things will come off. I think that’s the other thing I would say, and I think everybody understands that not everything that’s on that shopping
List is going to be in the bag at the end of the visit, you know. But if some of these things come off, as I believe they will, and if they come off to the level that they have the potential to,
These are things that will have a big impact on the city of Dundee, that will have a big impact on the Tay cities region and they’ll have been driven out of this University and by talented individuals who are here at the moment, whether that’s a staff or students or whatever,.
That’s the general flavour from me and I’m going to stop at that point. Thanks, David. By the way, you’re wrong. I’m always wrong. They’re all going to work. The shopping bags are going to be full and there’ll be additional things as well. Well, now, folks, David called it out.
And what I didn’t see earlier is amongst that long list of people – and it is quite a long list of people-that we need to pay great thanks for. And I can see Morag Martin, Zarah and Mike Ferguson who’s here – that there’s a whole range of people who have been incredibly influential
In helping us get to that Life Science Innovation Hub coming out the ground. But one of the people who’s done most on that is indeed David himself, because although David is a newly appointed VP, he’s been with us for, what, four years now?
Three years now, three and a bit, but you here before. So he was director of Research and Innovation beforehand. And David has been really influential in helping us take financial gain out of Exscientia, delivering on the Innovation Hub and the deals there.
And also in ensuring that we got to the Octopus Venture was number one for spin-outs. So thank you, David, and I’m sure that there’s a lot more to come. Now we’re going to shift gears a little bit, but not that far,
Really, given so much of the things we’re talking is about life sciences. What we’re going to shift to now is Liz, Liz Miller. Liz is a newly appointed professor. You’ve been here, what, six months now, Liz? So on, so forth? Liz came to us from a very, very prestigious laboratory
For molecular biology, the MRC, LMB in Cambridge? Cambridge. I always think ‘is it Cambridge or Oxford?’. And given that I spent time in Cambridge at a biotech company, it has to be Cambridge. By the way, David, I was the Cambridge Science Park and it was about the size of the Technopol,
At one of the two biotech companies at times a long time ago, I admit. But look what they can do – and anything they can do, Dundee can do better. Liz is an outstanding biologist. She focuses on membrane biology and she’s going to
Give us a little bit of science and a little bit of data. And I said, I love data, but you promised to be gentle to the audience. Liz, over you for some biology. Thanks again and thanks to you all for coming.
It’s a real pleasure to get a chance to present our research to you and I hope I can bring you all along the way. So our bodies are made up of lots of different individual cells on the order of 30 trillion individual cells, are compartmentalised different function of all of the different things
That our bodies have to do. So our brain cells will communicate and organise thoughts and coordinate all of the processes by working together. Our liver cells will process the alcohol we had for dinner last night by working together, muscle cells will do work for all of us. And so, the basic building
Block of all of our bodies is cells, but within cells it’s actually proteins that do the work. And we can think of proteins as protein machines that are created from the genetic blueprint in the DNA that we have. And that DNA is then decoded into protein machines
That are actually what do the work of different cells. And so this beautiful cartoon or watercolor painting actually by a wonderful artist, David Goodsell, depicts the interaction between two neuronal cells. So this is one neuronal cell on the bottom, and this is its border, it’s cell membrane, and this is a second
Neuronal cell on the top with its border, its cell membrane. And this cell is in the process of releasing chemicals, neurotransmitters that will be perceived by protein blobs on the surface of the communicating cell. And that signal will be understood by that cell and the signal will be transmitted
To have an output within this second cell all through the work of individual proteins. So it’s protein machines that do the work, that actually make cells do what they need to do in our bodies. And what my lab is interested in understanding is how those protein machines get made
And how those protein machines get delivered to the right spot in each cell so that they can do the work that they need to do in the right place and at the right time. And so specifically, what we look at are about the 10,000 proteins, 10,000 different types
Of proteins, again, this corresponds to about a third of your genome. So about a third of your genome encodes for protein machines that will be secreted from the cell, that leave the cell and travel through the body to do different types of functions and communicate with different other types of cells.
And so we have about 10,000 proteins that are secreted sent outside the cell. And I’m going to wander around a little bit so I can point to a little bit better these kinds of secreted proteins do all sorts of things. So certain types of white blood cells
Are dedicated to secreting antibodies that fight infection. Your intestinal cells will secrete enzymes that help digest the lunch that we just ate. Your tissues, hair and skin and connective tissues are made up by secreted molecules called collagen and keratins that form the structure that holds all of our tissues together.
And very important in diseases like heart disease are the cholesterol molecules that are secreted by cells that travel through the body and can do harm and actually good things as well. And so it’s this process, these 10,000 types of different proteins that get sent
Outside of an individual cell, that is the focus of what my lab studies. Oops. Okay. And so just like our body is compartmentalised into different cell types, our cells are compartmentalised into different structures called organelles. And again, that serves to compartmentalise different functions
So that different parts of the cell can do exactly what they need to do. So this is zooming in on a type of blood cell called a plasma cell, using an electron microscope to really visualise internal structures within this cell. This big blob in the middle is the nucleus.
This houses the genetic material that is the blueprint for life and for each of us as individuals. These small little blobs are mitochondria and mitochondria make the energy, the ATP that powers all of the work that our bodies need to do. And these sheets of structures are called the endoplasmic reticulum.
And this of course is the best organelle in the cell because this is the organelle that makes all of those 10,000 secreted proteins that need to get delivered outside of the cell. And this is the focus of what my lab studies. So again, these are these sheets of membrane
Enclosed structures is the endoplasmic reticulum. And this again is a beautiful illustration by David Goodsell that shows sort of the protein blobs that are associated with the endoplasmic reticulum, which is here delineated in green. This pink blob is a ribosome, this is the protein machine that makes other proteins.
And so this ribosome sits on the surface of the endoplasmic reticulum and through another protein channel pumps newly synthesized protein as it’s being made into the lumen of the endoplasmic reticulum. And so in fact, this particular cartoon is showing the biogenesis of antibody molecules shown here is this sort of beige blob.
And what will happen is that these newly synthesized proteins will fold into the correct three dimensional structure within the lumen of the endoplasmic reticulum. And then those proteins get captured into vesicles that bud off from the endoplasmic reticulum. And that’s what’s happening here. So another set of cytoplasmic proteins that bend the membrane
And bend that structure and populate the right proteins into that structure. And it’s this process that I want to tell you about today of how a cell makes a vesicle carrier and populates it with the right kinds of proteins and how we can manipulate that process hopefully for therapeutic benefit. Okay.
So to come back to this sort of cartoon idea, there’s lots of these different kinds of secretory proteins that need to be delivered to different destinations and secreted outside the cell. They start their life in the endoplasmic reticulum and then they all transit from the endoplasmic reticulum
Through a set of intermediate carriers that are called COPII vesicles. And these vesicles are little membrane bubbles that bud from the endoplasmic reticulum and then will fuse with the next compartment in the cell that’s responsible for doing a lot of sorting. And this is called the Golgi apparatus.
This process of capture into these COPII vesicles is what we’re interested in, in my lab. And we know a lot about this process. We know that there are specific proteins in fact called COPII. This is what the name stands for: coat protein complex type two.
So these proteins that coat the surface of the endoplasmic reticulum and make these membrane bubbles that bud off and with them carry the newly synthesised proteins that need to ultimately be delivered outside the cell. Okay. But how do proteins get into these bubbles and
What can we understand about that process and how can we maybe manipulate that process to change that secretion (…) of different cell types? And I can tell you about why that might be useful in a minute or two. Okay. So as I said, that protein machines do all of the work in cells
And this process is very much the same. What’s doing the work here and making sure that the right proteins get captured into these vesicles or bubbles is all driven by a series of protein-protein interactions. So this is a cartoon model of a protein called SEC24,
Which is one of these COPII coat proteins that coats the surface of the endoplasmic reticulum to make these bubbles. SEC24 will decode sorting signals that are found on cargo proteins that get captured into these vesicles. And protein SEC24 will interact directly with another protein called SURF4
That forms a bridge across the lipid bilayer or the membrane that separates one side of the endoplasmic reticulum from the other. And SURF4 in turn will interact with its own kind of cargo protein. So these protein-protein interactions are the key part of getting a newly synthesized protein like PCSK9 into these COPII vesicles.
And by understanding these molecular details of these interactions, we hope to be able to then manipulate how different kinds of cargo molecules can get into these vesicles. And so I’m going to tell you about this protein as an example, PCSK9, because it’s one of the first ones that we’re really interested in
And we’re interested in it for good reason. So PCSK9 is a regulator of cholesterol homeostasis in our cells. So there are human beings walking around who are mutants for PCSK9. They don’t have any PCSK9. And the effect of that is that they are hypocholesterolemic. So they’re actually healthier
Than most of us because they have less circulating cholesterol, so they have less heart disease, they’re less prone to all of these problems that are associated with high cholesterol. So PCSK9 and working out how to inhibit PCSK9 is a really attractive drug therapy
For people who may be resistant to statins and other kinds of treatments. At the moment in the clinic, there are antibody therapies that target PCSK9, but these are antibody therapies. They’re very expensive. They have to be taken intravenously as injections.
And so it’s not like taking a pill to lower your cholesterol very easily. But if we had a small molecule that could inhibit PCSK9, then that would be really great. And so what we’re working on is not actually a drug to inhibit PCSK9, but a drug to inhibit the secretion of PCSK9.
And just to sort of walk you through a little bit of what PCSK9 does is cholesterol, circulating cholesterol, LDL is taken off into cells through a cell surface receptacle, the LDL receptor. And what usually happens with PCSK9 is also in the bloodstream is that entire package gets internalized into the cell and delivered
To the lysosome where it’s all degraded, including the receptor. If patients or people don’t have PCSK9 or PCSK9 is inactive, what happens is the LDL receptor lets go of the LDL to get degraded, but it itself traffics back to the cell surface for another round of scavenging more LDL.
And that’s why PCSK9 mutant humans have lower circulating cholesterol because they have more of the scavenging material on the cell surface and they take up more LDL from the bloodstream. And so what our idea then is that if we can understand these molecular interactions – how is it
That PCSK9 gets captured into these vesicles at the very outset – and we can block those interactions with small molecule inhibitors, then we can prevent secretion of PCSK9 and lead to this situation where patients will or people treated with these molecules will have lower circulating cholesterol because they have extra LDL receptors
On their cell surface. Okay. So we set out to try and do this – to first just map the interactions, to map these protein-protein binding events that lead to PCSK9 interaction. And so we generated a system which makes use of firefly luciferase.
So this is a protein in fireflies that makes them glow in the dark. And so what we can do is to take this luciferase protein and split it into two parts so it’s broken and it doesn’t work, it doesn’t emit light.
And you fuse the two parts of those proteins to the two proteins that we’re interested in, in this case, SEC24, which is one of these coat proteins that makes vesicles and SURF4, which is the receptor that binds to PCSK9. And when these two proteins bind together that reconstitutes luciferase
And we can see a light signal that’s emitted. So when we get a protein-protein interaction, we have a readout of light. And so this is the data that I’m showing you here where if we have an interaction with SEC24 and SURF4, this is the wild type situation.
We have a nice big luminescent signal and that’s what we’re reading out here. And then what we can do is to go in and make point mutations to make genetic alterations that change the structure of SEC24 to block specific sites around the surface of SEC24
That we thought might be involved in this interaction with SURF4. And this is what I’m showing you here. This is a mutant called the B-site mutant. And when we mutate this surface pocket of SEC24, what we see is a decrease in this luminescent signal. So there’s less light being emitted
Because there’s less interaction between these two proteins. So this identification of the B-side on SEC24 as the site of the interaction for SURF4 is really exciting to us because there was a known small molecule that was known to block and bind that B-site.
And so if you think of the surface of SEC24 is sort of bumpy and there’s a little hollow here, that SURF4 will bind in – this small molecule plugs up that site and will prevent SURF4 from binding. And so we asked then if this small molecule 4-PBA,
In fact in our assay in a cell did actually prevent this interaction between these two proteins and reduce the luminescent signal from luciferase. And of course, I wouldn’t be telling you this if it didn’t. And so if we add increasing amounts of 4-PBA to our luciferase
Based signal where we see this light emitted when we have this interaction, if we add in more and more 4-PBA, we sequentially see less and less of this interaction, suggesting, in fact, that 4-PBA, really is perturbing this interaction between these two proteins.
So then, of course, this is the million dollar question: does this small molecule then inhibit the secretion of PCSK9, which is what we really care about? We don’t necessarily care about the interaction between SEC24 and SURF4. And so we wanted to then ask whether PCSK9 secretion can be inhibited
By blocking this interaction and by treating cells with 4-PBA. And so to do that, we used an experimental method called a pulse-chase analysis. So just to walk you through it very quickly, what this experiment does is we take a cell and we feed that cell radioactive amino acids.
So amino acids are the building blocks of proteins. And if you use radioactive amino acids to feed to cells, they’ll incorporate that radioactivity into any protein that’s being synthesized at that point in time. That’s the pulse labeling. So it’s labeling with radioactivity and a short pulse condition.
And so we pulse label cells by feeding them radioactivity. So then PCSK9 that’s made during that pulse labeling event will be radioactive. And then we chase over time to give the cell time to secrete that protein and release it into the cell media. And so that’s the chase part of the experiment.
And then we can isolate these specific proteins. And because radioactive is highly quantifiable, we can quantify the amount of radioactivity that’s associated with the protein that made it into the media relative to the amount that was found in when you just bust open the cell,
The total protein that was synthesized in that pulsed labelling experiment. And so then what we want to do is to do this pulse chase experiments plus and minus our small molecule and understand how PCSK9 secretion to the media is impacted by treatment with this drug. And so again,
Here we see the time, the increasing chase time. This is the secretion of PCSK9, radioactive PCSK9 secreted into the media. Over time, this increases nicely. So we get about 15% of what was made initially secreted within 80 minutes. And this blue line here is the amount that secreted after during treatment with 4-PBA.
So this really tells us that there’s a massive reduction in the secretion of PCSK9 when we block that interaction between SEC24 and SURF4. So this is really hopeful to us that we can design and develop small molecules that block specific protein-protein interactions and have the effect then of reducing secretion of specific proteins.
And now just to sort of highlight that this is not just specific for one particular set of molecules. I want to highlight that SEC24, the SEC24 protein, we all have four different versions of SEC24 encoded in our genomes and each SEC24 molecule has multiple different surfaces that interact with different proteins.
And so one could imagine if we had a small molecule that blocks one of these sites specifically, then we could affect secretion of antibodies. If we had a different small molecule, we could impact secretion of collagen. And so there are lots of diseases that might be associated or might be impacted
By selectively being able to inhibit branches of the secretory pathway, but leave the rest of secretion intact because of course you don’t want to inhibit secretion of gut enzymes and neurotransmitters and all of these other important things. And so this is the goal of my lab now
At Dundee is to work collaboratively with really fantastic colleagues at the Drug Discovery Unit to identify small molecules, take small molecules that we know and make them even better as inhibitors. We’re working with the human pluripotent stem cell facility to make these mutants in lots of different types of cell backgrounds.
So we can really understand in different cell types that have different jobs, how their secreted proteomes change in these different conditions so that we can then target specific different kinds of diseases that might work. Of course, we’re using proteomics as a readout for a lot of these experiments,
And we also have really fantastic collaborators that bring expertise in immunology that we don’t necessarily have ourselves. And so we’re sort of super excited for the work that we’re going to be doing here at Dundee. We’re funded very graciously by the Wellcome Trust, which was given –
Which is awarded as a Discovery Award, which affords eight years of funding to really have a long term view on how this is going to pan out. And so we have three fantastic new postdocs at Dundee Group supported by the remnants of the Cambridge Group.
And so with that, I thank you for your attention. Thank you. Thank you, Liz. Gosh, that was a canter. That was a canter. And I will check with some of the ex-biologists later how much they kept up with you. But it’s incredible the
You know, the connectivity, the story and narrative that you built there. And particularly if we can start to develop a number of small molecules, of course, small molecules the theory about small molecules is that small molecules are relatively easy to synthesize into medicines, stable medicines that people can take.
So small molecules are the target for a therapeutic drug sort of future. And my goodness me, you’ve got a whole host of potential diseases and quite focused the different cell types as well. So you can have really quite targeted therapies for individuals and also therapies that should be better
Tolerated than some of the rather sledgehammer type drugs that we see today. So really, really exciting stuff. Really exciting. So we go from fighting molecular membrane biology, not just membrane biology, because so much of that was inside that the cell as well too. Equally exciting, but maybe a slightly
More macro scale energy economics. Shawn Mu. Shawn has been you’ve been in Dundee for a little while, Shawn – 15 years. Yeah. It’s not such a little while, but of course, yeah, you got the badge yeah! But a newly promoted a professor. Congratulations.
In the Centre for Energy Petroleum and Mineral Law and Policy part of the School for Humanities, Social Sciences and Law. And Shawn – well, amongst other things that – you’ve the definitive textbook on the economics of oil and gas. So that alone is noteworthy, Shawn, but Shawn’s been looking at the
Rise of wind power and the economics of the impact of wind power on energy prices. So, Shawn, looking forward to this very much indeed. Please join me in welcoming Shawn. Thank you Iain for this very kind introduction and thanks everyone for coming. So last time I was lecturing
Here was three years ago in the autumn 2021 during the pandemic where we are required to keep to social distancing. It’s good to be back in this lecture theatre. So what I’m going to talk about today is ‘What Blows with the Wind’. Obviously, I’m a energy economist.
I’m going to tell you a little bit about what the results of the wind, where the wind blows to our energy price. So here, in this 15 minutes. I plan to speak a little bit about some of the basic facts about the wind energy in the UK. And then I will share
Some of the latest research I have been doing with some of my PhD students; on how has the growth in wind energy impacted electricity price and emissions? So because as everybody knows, the wind will play an important role in the transition to net zero.
And so this is something that we have been doing, looking empirically how the wind expansion impacted on our electricity bills and emissions. A little bit, unfortunately. So I’m looking at these empirical data and empirical evidence. The data is a little bit old a few years old, but not too old,
From 2010 up to 2024. So here are some of these basic facts. To state the obvious wind energy is cheap to generate because well, it generates, as long as the wind blows, it can generate. It does not require to burn fuels. So there are no almost no operational costs, no fuel costs.
But it is expensive to build. The construction cost of wind on a per kilowatt hour basis is almost three times that of the gas-fired CCGT (a combined cycle gas turbines). So it’s more expensive. And that’s why in the recent,
In the last half year or so, if you pay attention to the headline news, so here in the UK, we use the auctions to auction some of these wind offshore wind and then the latest round was initially last year in September. So the Financial Times says there were nobody come off
For these offshore wind because the Government set the limit low. And then later on in November, the Financial Times reports that the Government has increased the cap for the wind energy, so it increased by a 66% to £73 per megawatt hour. So that’s a long effect.
It is important for the electricity price because that’s the, you know, the fact that it is cheaper to generate. The second point that it is zero emission at the point of a generation. But not if you look at the form of the life cycle perspective, you know, when you build
Or manufacture a wind base, it does have some CO2 emissions but it is very low. The lifecycle of these were low. And finally obviously it depends on the weather, if the wind does not blow, you cannot generate. So that’s what we call the intermittent effect.
So that means that in the future if we have a larger amount of wind (energy) in the electricity system, you always need something to back them up and also you need some other resources to back them. And so that’s why we look at these to get to the issue, I guess. Yeah.
So I’m looking at how does this expansion on wind energy for the past ten years, 50 years, has impacted on our intraday wholesale prices as well. 2 – We’ll look at the CO2 emissions. We will look at the system cost. So it’s not just to look at the wholesale price.
So this slide shows the installing wind energy capacity for… this is almost 20 year or 15 years. So this the growth were fast, particularly starting from May 2000. So to look at the last 15 years from 2006/7, it’s almost grew by 15 times so far, from a little less than two –
This is the megawatt two – gigawatts to a little under 30 gigawatt. So these almost grew by 15 times. So obviously the wind….so the one bad thing about the wind is not all the wind capacity can generate all the time, it only generates when the wind blows
And so for the onshore wind , typically the utilization rate is about 25%. The offshore [capacity] is much higher at about 40%. So that’s how the wind will translate to generation. Now, this is of the overall electricity generation mix from again, from 1996 to 2022.
So this blue area or green is the wind is including both onshore and offshore wind – it has increased quite a lot from before 2005. Since 2005 it is almost negligible. Now is almost a quarter. 25% of the total wind we get. The expenses – the most expensive is the wind.
Coal has almost zero output. That’s due to reasons I will come back to. Now so what we specifically look at in this research is, you know, we look at how all of this will impact on the electricity price and so on he left hand side of this picture, this is the total load.
The load you know, in the electricity industry and all the industry, you know, the demand is called load. Okay. So that is the total demand. The demand between 2009 and 2018 has been reduced. So you can see it reduced quite a bit. For a variety of reasons: because over time
Our energy system becomes more efficient, the use of energy becomes more efficient. Also, the industry becomes lighter. So you have many industries, many popular industries become smaller. And so the total demand has reduced, but the electricity price has actually not reduced. So it has increased.
So the one question I tried to answer here is what other factors contributed to this price change? Right. I will skip that slide. So let’s look at the hours on average for a day. The UK electricity system use a half hour settlement period, 48 periods in a day.
So this is the total load and the total wind generation across the 48 settlement periods across the hours of a day. So you can see the good thing for UK, the wind in the UK is actually is positively correlated with the load, with the demand.
So during the peak hours, when the wind generates more – this is different from before, you know for other some of the other areas and regions. Before I came to live in Dundee, I worked a year in the States, models of the electricity system in Texas. In Texas, you know, during the
Peak hours, you see in the summer afternoon there is no wind. In the UK we have higher demand and high wind – that’s good. So what are the factors we look at? Obviously the demand change and then the gas price, because the gas price has increased, has increased by about
45% between 2009 and 2018. Coal price has also increased by about 25%. [Also the] Carbon price. Carbon price wise, you know, the UK was part of the EU ETS. Now the UK has its own emission trading system, so you need to pay a carbon price. Also there is a carbon supporting scheme.
Carbon price supports the scheme, called CTS. So there’s all this carbon price and so the carbon price, in the end, between 2009 and 2018 has also more than doubled. So we look at all these different factors and how these factors contribute to this electricity price.
So this is one of the key result slides. So this [X-axis] is of course hours. You can see the wind as the gigawatt hours of daily wind. So as in one gigawatt hour , how it can increase or when it will reduce the electricity price. So this is just for one gigawatt hour.
On the next slide, I will show you more measurables, you know, what has been done. So the important thing here is you can see almost every half hour the electricity price has been reduced associated with one Gigawatt hour of electricity increase. And so this is a look at how has it been doing
For the electricity price, Our wholesale electricity price between 2009 and 2018. So this over a ten year period. So as so a lot of changes. So this we look at the you know, how each of changes will do in contributing to our electricity price. So wind has reduced electricity price.
So looking at this across the time period it has reduced price by about three, £3.35. The other one is the load. The load demand reduce the price quite significantly there. Obviously the high is the natural gas price. This is narrow group. The price has increased,
There was a more positive impact – it increased price, electricity price and then this one, CPF means is the carbon price. Global coal – is essentially the current price. So in a nutshell basically. So these are gas price and as the carbon pricing increases, both of the price has increased because coverage
Has increased more than double and the gas price has increased by 45%. Thus has increased, causing electricity price by almost £15 per megawatt hour. The expansion of wind has reduced the electricity price. And so that’s why at the end we see the also electricity price has been increased. This is the
Contribution to the carbon emissions. So obviously we are in the process to drive into the net zero. So wind has contributed to the electricity, the carbon emission reduction over this ten year period. So I look at this as a contributor to about 25 million tons of carbon emission reduction.
So the whole UK over these ten years period from the carbon emission from electricity generation has been reduced by 85 million tonnes per year. So the expansion of wind has contributed to the 20 or 25 million tonnes. Load reduction has 41% reduction. So the other thing is, carbon
Price has an important negative effect as well. So it will reduce the carbon emissions by 14 million tonnes. Now gas price because of gas pricing, when gas price increases, it makes coal relatively cheaper. So the gas price increase actually has a positive impact on the carbon emissions.
The other thing is about the consequences of electricity system costs. What is the electricity system cost? The electricity system cost is The electricity system operator used to pay the generators to whether to reduce some of the emissions for the generation or for some other generators they need to stand by.
To provide the so-called ancillary services. So one of the major costs factors is called constraint. Constraint is what the system operator pay all the weather generators to cut down their generations. So there is a positive correlation. We also estimated how these different capital cost is associated with a cost of one megawatt hour
On wind generation. So the total cost is £1.14 associated with one megawatt for generation. So in all I also look at o 2009 and 2018. So the actually the total system cost has increased by about £5, associated with the wind expansion
So that’s – ah I see I have one minute – my conclusion. So basically it is so the wind generation has significantly lowered the electricity price per hour and then the load reduction and the increased wind are the two most important factors
To lowering the price, while the gas and carbon price increase price and then there’s load reduction, carbon pricing and the wind all contribute to the CO2 emissions reductions. Okay. Thank you. Well, Shawn, anybody that thinks economics is the dismal science after that, after your performance just is completely wrong. And anybody who thinks
Energy economics is simple, you know now, it’s not. It’s a very complex, multifactorial set of issues. But thank goodness that one of the assets we do have of these islands is wind – sometimes too much. Hopefully we’ll continue to see wind energy contribute to price moderation, but also to sustainability.
It is fantastic, the work that you do, and CEPMLP does around helping us create that transition to what Graham talked about this morning, that transition to net zero and that transition to sustainability. So three quite different, but certainly inspiring and very interactive and a kind of multidisciplinary approach presentations this afternoon.
Perhaps colleagues, it’s time for you to well, we’ve got a shade under 15 minutes to ask questions and I’m sure there are plenty of questions piling up for you. So it’s hot seat type up enjoyment, fun of the stage. So just to remind you, David spoke to us about enterprise and economic transformation.
Liz talked to us about protein secretion and the impacts of influencing protein secretion disease outcomes. And Shawn talked to us about energy and transitions and particularly the role of wind power and in both creating that with sustainability and also keeping some of the prices down,
Although it might not feel it’s lowering the energy bill coming through the door. So in the room or beyond the room, who’d like to start with some questions. Well done. So there’s one here, one there, so it’s – one, two, three. I’ve got a question for David.
You focus in your talk very much on Dundee and the economic impact on the city. How about wider economic impact of your role and the focus across Scotland and the UK? I mean in particular in relation to what companies do we work with and what opportunities do we look for? Thanks.
I mean, I think first of all, that company income – typically for research or for research and development type activity, but it may be for other activities – I think that is within the scope of the role. But I think that we are
Probably looking at, you know, I know conceptually we are not going to transform the economy of anywhere else on the basis of what we’re doing here. So because of the transformation bit, I concentrated locally. I think the research that the University does, lots of the research
That University does, has the potential to be commercialized successfully all across the place. But it’s transformation of our city that’s my preoccupation, I think. Thanks David, thanks Daniela. Next one. Hi, thank you all three very much. My question’s for Liz. It might seem stupid one and it’s based on it, but appear.
Be careful, he’s a (…) geographer. My limited knowledge of the cell structure of proteins, which mostly was derived from watching news during the pandemic, I was learning how much of what you were describing is visible in the high end microscopy. How much of it is inferred by looking at chemical changes?
So in a practical level, it’s almost all inferred we have lots of different ways of detecting that material that’s secreted, and that’s the easiest way to do it. So we can use antibodies that specifically recognize individual proteins. That’s how we do that pulse chase experiment to pull on and identify an individual protein.
The other thing that we do in the lab is to use mass spectrometry, which is a method that identifies all of the proteins in any given sample. And so what would do, for instance, is in our cell culture where we’re growing these cells in a test tube
Is spin out the cells by centrifugation, they’re heavy and take the proteins from the cells and the proteins that are secreted and then put them through the mass spectrometer. And that will tell us all of the proteins so we can identify and quantify all of the proteins that way.
Proteins themselves are visible in the electron microscope, but we can’t yet determine exactly their structure or their abundance with that method. But the technology is moving forward. And that’s the goal, in fact, is to be able to visualize individual proteins. Thank you very much So it’s a little bit of artist’s impression.
Absolutely. It’s up there. But of course, many of our colleagues in DJCAD, are leading on as well. But what fantastic heuristic it is for us to think through the mechanisms and the interactions. And thank you for these wonderful pictures. We appreciate them. Next one. I my question is also to Liz.
So my question is, so based on your research, do you have a recommendation for daily protein intake or minimal amount of protein intake? So, you know, because that’s sort of a nutrition problem of where your cells are getting their building blocks from.
So the reason we need to eat dietary protein is to make sure that that then gets broken down into these amino acids and those are the building blocks to make up our own proteins. And so that’s why we need to ingest protein is so to fuel our own protein synthesis within our bodies.
So you need protein, but equally we break down our own proteins and there’s a lot of turnover within our bodies. And so our bodies do both things. So you need a certain amount of protein. It doesn’t necessarily matter the source. A protein is a protein from your body’s point of view.
There may be differences, talking about synthetic proteins, synthetic meats and things like that, that’s a whole different question. But from your body’s point of view, a dietary protein is dietary protein and your body needs it to make those building blocks so it can then build up its own proteins.
Does that answer your question? It sounds like a bit of a conversation for coffee. Absolutely, yes. I’ve got two more questions lined up in the room and then we’ll go online. But Mike. I have a question for Shawn. Thank you very much for your talk.
The economics of energy storage are critical as we transition to net zero. Would you like to just add some commentary on that – about what we should be doing as a nation in terms of energy storage? Okay. Yes. So there’s the storage. There are two things.
One is obviously, it is important that there is a long duration and shorter duration of the storage. The longer duration is particularly those like the power storage. So obviously depends on the geography, right? So you have to have a reservoir. And more importantly for the electricity balancing purpose is primarily the battery system.
So is a few hours -still people talk about hours as a long duration. The problem there is the cost – that it’s expensive but this is definitely something that I they actually include there. So you know we are how is didn’t look at this and there’s no well yeah
So that’s the if we really really in this particular with a lot of modeling renewables is a thank you Thank you Shawn. Next one. I have a question for Professor Miller. I’m a clinician and so I’m excited about seeing your research.
I wondered how far along you are in your research or how early on you are? Because I saw you had AstraZeneca was one of your contributors and to getting a working hypothesis for them to start moving towards clinical trials
Or some kind of some idea of how you could transfer that to clinical practice? Yeah, So that’s a great question. Thank you. So the collaboration with AstraZeneca, it was through a collaborative grant process, through the LMB, which is my previous home
That was really – it’s called Blue Skies Research, and it really was – basic discovery to marry interests of the two institutions. And AstraZeneca has a long term interest in PCSK9 specifically, and they helped us to develop these assays. In fact, weirdly, they didn’t want to support the drug discovery
Aspect of that because they didn’t want to get into small molecule discovery. And so that’s what we’re doing here with the Drug Discovery Unit. So what I would say is that this one small molecule we have this 4-PBA, is a pretty crappy drug. We have to use very high concentrations.
It has knock on effects. What we really want to do is that’s the handle that, sort of the chink in the armor, and that with the drug discovery unit, we can have structural biology approaches. We have to sort of get into some jargon.
We have crystal structures of some of these proteins and so we know exactly the molecular details of some of those interactions. With machine learning and computational approaches, I’m hoping we can computationally design better small molecules and we have this assay now that the Drug Discovery
Unit, the National Phenotypic Screening Centre’s here in Dundee, will help us do drug screens that I am hopeful will really be the next step. So we’re still at very early stages, but I think there’s enormous potential and the fact that we have one small molecule in hand
And the proof of principle is actually the key advance. But a focus on small molecules creates opportunity. Absolutely. Fantastic. Okay, So I’ve got a question Shawn, for you from somebody online, and it’s two questions. One is how can constraint costs be reduced in a future generation?
And secondly, kind of takes up a little bit on what Mike Ferguson was asking before as well as generation infrastructure, do you think we need more transmission infrastructure between Scotland and England, where net generation and net load is really quite differently distributed across the country? Thank you.
So these two questions actually are related. The constraint cost is also about the system that transmits – so as we have more wind generation, there is definitely demand for more transmission. Transmission lines, with way more transmission lines between these countries the constraint cost they used to pay for generators to reduce their generation.
Well, they can be reduced obviously there is a cost of building this transmission. So that’s the same thing actually. So I think the second question is also the same. So you know, I presented this thing in Tanbury, Oxford. So afterwards there was a company
Who approached us to see what we can do to do some of that. Particularly to wind. What can we do to make it more, you know, available for sort of houses – this sort of thing. I’m going to use chairman’s privilege because we only got a couple of minutes
Left. I’m going to ask the last question. David, it’s coming at you. So, you know, we are doing, you’re doing all this great work around enterprise and economic transformation here in Dundee. How do we link what we are doing here best in Dundee
To the future of the Scottish economy as well as the Dundee economy? How do you move away from having Glasgow doing a Glasgow thing, Edinburgh doing an Edinburgh thing, Dundee doing the Dundee thing, Aberdeen doing the Aberdeen thing and have more of an ecosystem
Of future economic transformation within the areas that you’re involved in? Yeah, I mean I think that there’s been an awful lot of strategy has been published by public agencies over the last few years. Some have been good, some have been not so good.
I think the Scottish Government’s innovation strategy that was published in May 2023 is one of the better documents that’s come out of this kind of space, because I think it’s the first time that there’s been an explicit recognition by Scottish Government in particular that it’s not this idea of
The only place in Scotland for Life Sciences is Edinburgh Bioquarter, you know, they’ve recognized, I think, that they can go for a cluster based approach where the cluster could be distributed throughout the country. And I think that if we can hang on to what was in that strategy, I think all universities would
Benefit and I think it would be in Scotland’s benefit. The problem, of course, is we’ve touched on lots of people today, including at the court session, touched on the fact that the Scottish Government isn’t awash with cash at the moment to make these kind of strategies become more real.
But I think in terms of the pointers that have been made – that Scottish innovation strategy to me perhaps is the most encouraging one and because it is approaching a whole Scotland approach and I think we can be a good citizen
And not by reaching out to the other universities that we already partner with. And I think that’s probably our best chance of benefiting from that approach. So Scotland as a cluster and us trying to take the lead in making it a reality.
You know, making the connections happen, I think is an area where because there’s been investment before and things that are supposed to connect the sector, but the investment tends to be in the place that’s already currently the biggest beneficiary and they don’t always use it to reach out to the others. Excellent.
Well, I’m sorry to say that’s us run out of time for this session. Coffee’s available, I’m sure tea as well outside, but please join me once again. Thank you for the first three speakers Shawn, Liz and David. Thank you.