̽��ֱ�� of Cambridge - Tuomas Knowles

10 Cambridge spinouts forging a future for our planet

skbf2 — Fri, 25 Oct 2024 10:07:50 +0000

10 companies taking Cambridge ideas out of the lab and into the real world to address the climate emergency.

Making things happen: the importance of knowledge exchange

skbf2 — Mon, 08 Nov 2021 16:00:33 +0000

Knowledge exchange has been a personal passion for me, ever since my first job as a Teaching Company Associate (Now Knowledge Transfer Partnerships), managing a knowledge exchange project with Cardiff ̽��ֱ�� and a tech start-up company. That experience sparked my fascination with the impact of university research on the wider world. Since then I’ve been fortunate to pursue this interest, working with universities and businesses across the UK in a range of different roles. I was delighted to get the opportunity to come to Cambridge where there are so many exciting opportunities for knowledge exchange.

̽��ֱ��rewards of the job

It is hugely satisfying when you are able to identify and nurture synergies between businesses and universities to achieve things neither could do on their own. For example, one of my tasks is to manage the EPSRC IAA Follow-on Fund at Cambridge. I am often told by academics how critical a relatively small injection of cash at the right time can be in helping them move an idea on to the point where it can attract more significant investment or industry support.

Fluidic Analytics, a spin-out from the Department of Chemistry, is a fantastic example of this. During the course of his research, Professor Tuomas Knowles invented a new method for studying proteins and their behaviours which he turned into a lab-scale prototype. It was thanks to the IAA Follow-on Fund that he was able to keep the project going until he could secure the investment needed to commercialise it. ̽��ֱ��company now employs more than 60 people and has raised more than $40 million in funding.

̽��ֱ��IAA has also played a pivotal role in collaborations with two of the ̽��ֱ��’s business partners, Rolls-Royce and Arm. An IAA Knowledge Transfer Fellowship enabled Bryce Conduit at Rolls-Royce and James Taylor in the Whittle Lab (pictured above) to use machine learning to predict how much damage an aeroengine’s compressor blades can sustain before they need to be repaired or replaced. To solve the problem, the pair developed a radical new approach to rapid prototyping that has the potential to revolutionise the way engineers design and optimise turbomachinery.

IAA Funding also enabled two postdocs to be seconded to Arm for a year to help it assess the feasibility of building a ‘proper’ industry-scale prototype of the ground-breaking digital security concepts being developed at the ̽��ֱ��’s Department of Computer Science and Technology. If adopted, this will affect virtually all of us, improving the security of the billions of phones, computers and myriad devices that rely in Arm technology.

Sometimes we talk about technology as if is a discrete entity that can be boxed up and exchanged for money. In practice, of course, it is not that simple. Technology is also about the know-how that resides in a researcher’s head. People are at the heart of knowledge exchange, whether it is someone from Rolls-Royce coming to work in the Whittle Lab or ̽��ֱ�� researchers going to work at Arm. In both cases, it gives them an opportunity to immerse themselves in a different world which can be hugely beneficial for the individuals concerned as well as paving the way for future collaborations.

Making connections

We are fortunate at Cambridge that we have a strong track record of both entrepreneurship and collaboration with industry and other external partners. Many academics have achieved amazing things through the commercialisation of their research – and are expert at doing so. But how do you make sure, in an organisation of our size, that everyone who wants to get involved in knowledge exchange knows how to? That’s where the ̽��ֱ��’s network of knowledge exchange professionals comes in. One of our roles is to unearth that tacit knowledge within the ̽��ֱ��, share it widely and develop best practice so that everyone can benefit. ̽��ֱ��other is about trying to connect, translate and mediate between the different worlds of academia and business and policy.

Laying the groundwork

An often overlooked aspect of knowledge exchange is the importance of timing. An external partner has to be at exactly the right point in their development lifecycle to need our input. That need has to align with an academic or research group having the interest and capacity to pursue the research problem. There is a certain amount of luck involved in getting the timing right but, to borrow a well-worn phrase, ‘the harder I work, the luckier I get’.

As knowledge exchange professionals, we spend a lot of time and effort doing the groundwork, forging connections and sharing information, often without a clear idea at the outset of what will bear fruit. You know something will happen, you just don't know what. Both sides - universities and businesses – have to be prepared to make this kind of investment of time and resources.

A lot of people are in academia because of their natural curiosity: they want to understand how things work and why they are the way they are. By connecting them with the outside world, I can give them access to interesting new problems and help them turn their ideas into realities that go on to make a difference to people’s lives. Making that happen is a genuinely rewarding task: I still can’t quite believe my luck that I ended up here.

Claire McGlynn, Head of Impact Acceleration, Research Strategy Office

November 2021

Read all our Business and Enterprise blog posts here

Bryce Conduit (left) and James Taylor in the ̽��ֱ��'s Whittle Laboratory

Scientists identify the cause of Alzheimer’s progression in the brain

sc604 — Fri, 29 Oct 2021 18:00:23 +0000

̽��ֱ��international team, led by the ̽��ֱ�� of Cambridge, found that instead of starting from a single point in the brain and initiating a chain reaction which leads to the death of brain cells, Alzheimer’s disease reaches different regions of the brain early. How quickly the disease kills cells in these regions, through the production of toxic protein clusters, limits how quickly the disease progresses overall.

̽��ֱ��researchers used post-mortem brain samples from Alzheimer’s patients, as well as PET scans from living patients, who ranged from those with mild cognitive impairment to those with late-stage Alzheimer’s disease, to track the aggregation of tau, one of two key proteins implicated in the condition.

In Alzheimer’s disease, tau and another protein called amyloid-beta build up into tangles and plaques – known collectively as aggregates – causing brain cells to die and the brain to shrink. This results in memory loss, personality changes and difficulty carrying out daily functions.

By combining five different datasets and applying them to the same mathematical model, the researchers observed that the mechanism controlling the rate of progression in Alzheimer’s disease is the replication of aggregates in individual regions of the brain, and not the spread of aggregates from one region to another.

̽��ֱ��results, reported in the journal Science Advances, open up new ways of understanding the progress of Alzheimer’s and other neurodegenerative diseases, and new ways that future treatments might be developed.

For many years, the processes within the brain which result in Alzheimer’s disease have been described using terms like ‘cascade’ and ‘chain reaction’. It is a difficult disease to study, since it develops over decades, and a definitive diagnosis can only be given after examining samples of brain tissue after death.

For years, researchers have relied largely on animal models to study the disease. Results from mice suggested that Alzheimer’s disease spreads quickly, as the toxic protein clusters colonise different parts of the brain.

“ ̽��ֱ��thinking had been that Alzheimer’s develops in a way that’s similar to many cancers: the aggregates form in one region and then spread through the brain,” said Dr Georg Meisl from Cambridge’s Yusuf Hamied Department of Chemistry, the paper’s first author. “But instead, we found that when Alzheimer’s starts there are already aggregates in multiple regions of the brain, and so trying to stop the spread between regions will do little to slow the disease.”

This is the first time that human data has been used to track which processes control the development of Alzheimer’s disease over time. It was made possible in part by the chemical kinetics approach developed at Cambridge over the last decade which allows the processes of aggregation and spread in the brain to be modelled, as well as advances in PET scanning and improvements in the sensitivity of other brain measurements.

“This research shows the value of working with human data instead of imperfect animal models,” said co-senior author Professor Tuomas Knowles, also from the Department of Chemistry. “It’s exciting to see the progress in this field – fifteen years ago, the basic molecular mechanisms were determined for simple systems in a test tube by us and others; but now we’re able to study this process at the molecular level in real patients, which is an important step to one day developing treatments.”

̽��ֱ��researchers found that the replication of tau aggregates is surprisingly slow – taking up to five years. “Neurons are surprisingly good at stopping aggregates from forming, but we need to find ways to make them even better if we’re going to develop an effective treatment,” said co-senior author Professor Sir David Klenerman, from the UK Dementia Research Institute at the ̽��ֱ�� of Cambridge. “It’s fascinating how biology has evolved to stop the aggregation of proteins.”

̽��ֱ��researchers say their methodology could be used to help the development of treatments for Alzheimer’s disease, which affects an estimated 44 million people worldwide, by targeting the most important processes that occur when humans develop the disease. In addition, the methodology could be applied to other neurodegenerative diseases, such as Parkinson’s disease.

“ ̽��ֱ��key discovery is that stopping the replication of aggregates rather than their propagation is going to be more effective at the stages of the disease that we studied,” said Knowles.

̽��ֱ��researchers are now planning to look at the earlier processes in the development of the disease, and extend the studies to other diseases such as Frontal temporal dementia, traumatic brain injury and progressive supranuclear palsy where tau aggregates are also formed during disease.

̽��ֱ��study is a collaboration between researchers at the UK Dementia Research Institute, the ̽��ֱ�� of Cambridge and Harvard Medical School. Funding is acknowledged from Sidney Sussex College Cambridge, the European Research Council, the Royal Society, JPB Foundation, the Rainwater Foundation, the NIH, and the NIHR Cambridge Biomedical Research Centre which supports the Cambridge Brain Bank.

Reference:
Georg Meisl et al. ‘In vivo rate-determining steps of tau seed accumulation in Alzheimer’s disease.’ Science Advances (2021). DOI: 10.1126/sciadv.abh1448

For the first time, researchers have used human data to quantify the speed of different processes that lead to Alzheimer’s disease and found that it develops in a very different way than previously thought. Their results could have important implications for the development of potential treatments.

This research shows the value of working with human data instead of imperfect animal models

Tuomas Knowles

National Institute of Mental Health, National Institutes of Health, USA

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‘Vegan spider silk’ provides sustainable alternative to single-use plastics

sc604 — Thu, 10 Jun 2021 09:00:00 +0000

̽��ֱ��researchers, from the ̽��ֱ�� of Cambridge, created a polymer film by mimicking the properties of spider silk, one of the strongest materials in nature. ̽��ֱ��new material is as strong as many common plastics in use today and could replace plastic in many common household products.

̽��ֱ��material was created using a new approach for assembling plant proteins into materials that mimic silk on a molecular level. ̽��ֱ��energy-efficient method, which uses sustainable ingredients, results in a plastic-like free-standing film, which can be made at industrial scale. Non-fading ‘structural’ colour can be added to the polymer, and it can also be used to make water-resistant coatings.

̽��ֱ��material is home compostable, whereas other types of bioplastics require industrial composting facilities to degrade. In addition, the Cambridge-developed material requires no chemical modifications to its natural building blocks, so that it can safely degrade in most natural environments.

̽��ֱ��new product will be commercialised by Xampla, a ̽��ֱ�� of Cambridge spin-out company developing replacements for single-use plastic and microplastics. ̽��ֱ��company will introduce a range of single-use sachets and capsules later this year, which can replace the plastic used in everyday products like dishwasher tablets and laundry detergent capsules. ̽��ֱ��results are reported in the journal Nature Communications.

For many years, Professor Tuomas Knowles in Cambridge’s Yusuf Hamied Department of Chemistry has been researching the behaviour of proteins. Much of his research has been focused on what happens when proteins misfold or ‘misbehave’, and how this relates to health and human disease, primarily Alzheimer’s disease.

“We normally investigate how functional protein interactions allow us to stay healthy and how irregular interactions are implicated in Alzheimer’s disease,” said Knowles, who led the current research. “It was a surprise to find our research could also address a big problem in sustainability: that of plastic pollution.”

As part of their protein research, Knowles and his group became interested in why materials like spider silk are so strong when they have such weak molecular bonds. “We found that one of the key features that gives spider silk its strength is the hydrogen bonds are arranged regularly in space and at a very high density,” said Knowles.

Co-author Dr Marc Rodriguez Garcia, a postdoctoral researcher in Knowles’ group who is now Head of R&D at Xampla, began looking at how to replicate this regular self-assembly in other proteins. Proteins have a propensity for molecular self-organisation and self-assembly, and plant proteins, in particular, are abundant and can be sourced sustainably as by-products of the food industry.

“Very little is known about the self-assembly of plant proteins, and it’s exciting to know that by filling this knowledge gap we can find alternatives to single-use plastics,” said PhD candidate Ayaka Kamada, the paper’s first author.

̽��ֱ��researchers successfully replicated the structures found on spider silk by using soy protein isolate, a protein with a completely different composition. “Because all proteins are made of polypeptide chains, under the right conditions we can cause plant proteins to self-assemble just like spider silk,” said Knowles, who is also a Fellow of St John's College. “In a spider, the silk protein is dissolved in an aqueous solution, which then assembles into an immensely strong fibre through a spinning process which requires very little energy.”

“Other researchers have been working directly with silk materials as a plastic replacement, but they’re still an animal product,” said Rodriguez Garcia. “In a way, we’ve come up with ‘vegan spider silk’ – we’ve created the same material without the spider.”

Any replacement for plastic requires another polymer – the two in nature that exist in abundance are polysaccharides and polypeptides. Cellulose and nanocellulose are polysaccharides and have been used for a range of applications, but often require some form of cross-linking to form strong materials. Proteins self-assemble and can form strong materials like silk without any chemical modifications, but they are much harder to work with.

̽��ֱ��researchers used soy protein isolate (SPI) as their test plant protein, since it is readily available as a by-product of soybean oil production. Plant proteins such as SPI are poorly soluble in water, making it hard to control their self-assembly into ordered structures.

̽��ֱ��new technique uses an environmentally friendly mixture of acetic acid and water, combined with ultrasonication and high temperatures, to improve the solubility of the SPI. This method produces protein structures with enhanced inter-molecular interactions guided by the hydrogen bond formation. In a second step, the solvent is removed, which results in a water-insoluble film.

̽��ֱ��material has a performance equivalent to high-performance engineering plastics such as low-density polyethylene. Its strength lies in the regular arrangement of the polypeptide chains, meaning there is no need for chemical cross-linking, which is frequently used to improve the performance and resistance of biopolymer films. ̽��ֱ��most commonly used cross-linking agents are non-sustainable and can even be toxic, whereas no toxic elements are required for the Cambridge-developed technique.

“This is the culmination of something we’ve been working on for over ten years, which is understanding how nature generates materials from proteins,” said Knowles. “We didn’t set out to solve a sustainability challenge -- we were motivated by curiosity as to how to create strong materials from weak interactions.”

“ ̽��ֱ��key breakthrough here is being able to control self-assembly, so we can now create high-performance materials,” said Rodriguez Garcia. “It’s exciting to be part of this journey. There is a huge, huge issue of plastic pollution in the world, and we are in the fortunate position to be able to do something about it.”

Xampla's technology has been patented by Cambridge Enterprise, the ̽��ֱ��'s commercialisation arm. Cambridge Enterprise and Amadeus Capital Partners co-led a £2 million seed funding round for Xampla, joined by Sky Ocean Ventures and the ̽��ֱ�� of Cambridge Enterprise Fund VI, which is managed by Parkwalk.

Reference:
A. Kamada et al. ‘Self-assembly of plant proteins into high-performance multifunctional nanostructured films.’ Nature Communications (2021). DOI: 10.1038/s41467-021-23813-6

Researchers have created a plant-based, sustainable, scalable material that could replace single-use plastics in many consumer products.

It was a surprise to find our research could also address a big problem in sustainability: that of plastic pollution

Tuomas Knowles

Xampla

Packaging incorporating Xampla's plant-based plastic

Yes

Cambridge researchers awarded European Research Council funding

cg605 — Wed, 09 Dec 2020 17:14:16 +0000

Three hundred and twenty-seven mid-career researchers were today awarded Consolidator Grants by the ERC, totalling €655 million. ̽��ֱ��UK has 50 grantees in this year’s funding round. ̽��ֱ��funding is part of the EU’s current research and innovation programme, Horizon 2020.

̽��ֱ��ERC Consolidator Grants are awarded to outstanding researchers of any nationality and age, with at least seven and up to 12 years of experience after PhD, and a scientific track record showing great promise.

̽��ֱ��research projects proposed by the new grantees cover a wide range of topics in physical sciences and engineering, life sciences, as well as social sciences and humanities.

From the ̽��ֱ�� of Cambridge, the following researchers were named as grantees: Professor Vasco Carvalho, Professor Tuomas Knowles, Dr Neel Krishnaswami, Professor Silvia Vignolini and Dr Kaisey Mandel.

Vasco Carvalho, Professor of Macroeconomics and Director of Cambridge-INET, Faculty of Economics

Project title: Micro Structure and Macro Outcomes.

What is your research about?

“Research under the project MICRO2MACRO takes as a starting point the organisation of production around supply chain networks and, within these networks, the increasing dominance of very large and central firms. This renders a small number of firms and technologies systemic in that they can influence aggregate economic performance.

“Within this broad agenda, MICRO2MACRO explores issues surrounding, first, market power and pro-competitive policies and, second, innovation, productivity and the diffusion of new technologies. ̽��ֱ��project also partners with one global financial institution to unlock relevant real-time, highly granular data that is necessary to study some of these questions.”

How do you feel about being named a grantee?

“I'm ecstatic. First, because it recognises the combined effort of colleagues around the world in developing a new micro-to-macro research agenda and understanding macroeconomic developments via a new lens. Second, because it provides the opportunity to inject otherwise scarce resources into early career researchers and PhD students, thereby adding to the human capital in this research area. Third, because it further highlights a decade of collective efforts at the Faculty of Economics here at Cambridge and helps ensure its continued growth as a hub for the development of new approaches to decades old questions in economics.”

Professor Tuomas Knowles, Yusuf Hamied Department of Chemistry

Project title: Digital Protein Biophysics of Aggregation.

What is your research about?

“Our work is focused on understanding the basic molecular principles that govern the activity of proteins in health and disease. In particular we are interested in how proteins come together to form machinery and compartments that underpin the functions of a living cell, and what happens when these processes fail.

“ ̽��ֱ��ERC project is focused on understanding how proteins condense together to form functional liquid organelles, and how such compartments can gel and form irreversible protein aggregates associated with disease. Such problems have been challenging to study previously due to the very high heterogeneity of the structures that are formed which make observation by conventional bulk techniques challenging. We will be developing new single molecule approaches to study this phenomenon aggregate by aggregate and cell by cell, and in this way shed light on the connection between the physical and structural properties of protein assemblies and their biological activity.”

How do you feel about being named a grantee?

“I am truly delighted by this support of my research and that of my group, which will allow us to develop fundamentally new approaches for probing a process at the core of biological function and malfunction.”

Dr Neel Krishnaswami, Computer Laboratory

Project title: Foundations of Type Inference for Modern Programming Languages.

What is your research about?

“Many modern programming languages, whether industrial or academic, are typed. Each phrase in a program is classified by its type (for example, as strings or integers), and at compile-time programs are checked for consistent usage of types, in a process called type-checking. Thus, the expression ‘3 + 4’ will be accepted, since the + operator takes two numbers as arguments, but the expression ‘3 + ‘hello’’ will be rejected, as it makes no sense to add a number and a string. Though this is a simple idea, sophisticated type systems can track properties like algorithmic complexity and program correctness.

“In general, programmers must write annotations to tell computers which types to check. In theory, it is easy to demand enough annotations to trivialize type-checking, but this can easily make the annotation larger than the program itself! So, to transfer results from formal calculi to real programming languages, we need type inference algorithms, which reconstruct missing types from partially-annotated programs.

“In TypeFoundry, we will use recent developments in proof theory and formal semantics to identify the theoretical structure underpinning type inference.”

How do you feel about being named a grantee?

“Naturally, I am happy to find out that my research is valued in such concrete, material terms, and I'm delighted to have the opportunity to have the chance to support PhD students and postdocs working in this area. I also feel this shows off the best international character of science. I am an Indian-American researcher working in the UK, judged and funded by my European peers. Consequently, I keenly feel both the opportunity and responsibility to carry on the cosmopolitan tradition of scientific work.”

Professor Silvia Vignolini, Yusuf Hamied Department of Chemistry

Project title: Sym-Bionic Matter: developing symbiotic relationships for light-matter interaction.

What is your research about?

“With this ERC grant I aim to develop new platforms and tools to study how different organisms build symbiotic interactions for light management and ‘evolve’ new symbiotic relationships, in which one of the organisms is replaced by an artificial material to generate a novel class of hybrid which I link to call ‘sym-BIonic matTEr’ – BiTe!”

How do you feel about being named a grantee?

“I was very excited to learn that I had been awarded an ERC grant and I look forward to starting the project. It’s an amazing opportunity for my team and me!

“When you receive the evaluation response, you get an email notification that invites you to log into the EU portal to see the outcome of the evaluation. In those few minutes that it takes to open the right form on the platform, I experienced pure panic! When I finally open the letter, I had to read it three times to convince myself that I had been awarded the grant! It was a great day!”

Dr Kaisey Mandel, Institute of Astronomy, Statistical Laboratory of the Department of Pure Mathematics and Mathematical Statistics, Kavli Institute for Cosmology

Project title: Next-Generation Data-Driven Probabilistic Modelling of Type Ia Supernova SEDs in the Optical to Near-Infrared for Robust Cosmological Inference.

What is your research about?

“My research focuses on utilising exploding stars called Type Ia supernovae to measure cosmological distances for tracing the history of cosmic expansion.

“I lead a project to develop state-of-the-art statistical models and advanced, data-driven techniques for analysing observations of these supernovae in optical and near-infrared light to determine more precise and accurate distances.

“Applying these novel methods to supernova data from the Hubble Space Telescope, new ground-based surveys, and, in the near future, the Vera Rubin Observatory's Legacy Survey of Space and Time, we will pursue new and improved constraints on the accelerating expansion of the Universe and the nature of dark energy.”

Five researchers at the ̽��ֱ�� of Cambridge have won consolidator grants from the European Research Council (ERC), Europe’s premiere funding organisation for frontier research.

iStock.com/ BarrySheene

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Cambridge spin-out company wins £18m to fight Alzheimer's

plc32 — Thu, 24 Jan 2019 10:27:38 +0000

A biopharmaceutical company set-up by Cambridge academics from St John's College to develop drugs to treat illnesses such as Alzheimer's, Parkinson’s and more than 50 other related diseases has won £18 million in a Series A financing round.

Wren Therapeutics raised the funding from an international syndicate led by ̽��ֱ��Baupost Group with participation from LifeForce Capital and a number of high net worth individual investors.

Several of the company’s scientific founders are members of St John’s, including Professor Sir Christopher Dobson, Master of St John's, Professor Tuomas Knowles, a St John's Fellow, and Dr Samuel Cohen, the St John’s Entrepreneur in Residence.

Wren Therapeutics focuses on drug discovery and development for protein misfolding diseases such as Alzheimer’s and Parkinson’s and was founded in 2016.

Protein molecules form the machinery which carry out all of the executive functions in living systems. However, proteins sometimes malfunction and become misfolded, leading to a complex chain of molecular events that can cause long-lasting damage to the health of people affected and may ultimately lead to death.

This group of medical disorders are known as protein misfolding diseases. Alzheimer’s and Parkinson’s are widely recognised protein misfolding diseases, but others include type-2 diabetes, motor neurone disease and more than 50 other related illnesses.

Dr. Cohen explained: “Protein misfolding diseases are one of the most critical global healthcare challenges of the 21st century but are highly complex and challenging to address. Current strategies - in particular those driven by traditional drug discovery and biological approaches - have proven, at least to date, to be ineffective.

“Wren’s new and unique approach is instead built on concepts from the physical sciences and focuses on the chemical kinetics of the protein misfolding process, creating a predictive and quantitatively driven platform that has the potential to radically advance drug discovery in this class of diseases.”

Wren Therapeutics is a spin-off company from the ̽��ֱ�� of Cambridge and Lund ̽��ֱ�� in Sweden. ̽��ֱ��company is based at the ̽��ֱ�� of Cambridge, in the recently opened Chemistry of Health Centre, and plans on opening a satellite office in Boston, Massachusetts.

Professor Sir Christopher Dobson said: "Wren is built on many years of highly collaborative, uniquely integrated, interdisciplinary research that has uncovered the key molecular mechanisms associated with protein misfolding diseases.

"I am hugely enthusiastic about our ability to make tangible progress against these diseases and change the course of life for millions of people around the world suffering from these debilitating and increasingly common medical disorders.”

̽��ֱ��company will announce its board of directors shortly.

Wren Therapeutics secures £18 million in funding to tackle protein misfolding diseases.

"I am hugely enthusiastic about our ability to make tangible progress against these diseases"

Professor Sir Christopher Dobson

Dr Samuel Cohen, Entrepreneur in Residence at St John's and CEO of Wren Therapeutics

Yes

Scientists reveal plan to target the cause of Alzheimer’s disease

Anonymous — Mon, 24 Sep 2018 19:00:00 +0000

Academics at the ̽��ֱ�� of Cambridge and at Lund ̽��ֱ�� in Sweden have devised the first strategy to ‘go after’ the cause of the devastating disease, which could eventually lead to the development of new drugs to treat dementia. Their findings are reported in the journal PNAS.

“This is the first time that a systematic method to go after the pathogens – the cause of Alzheimer’s disease - has been proposed,” said Professor Michele Vendruscolo from Cambridge’s Department of Chemistry, the paper’s senior author. “Until very recently scientists couldn’t agree on what the cause was so we didn’t have a target. As the pathogens have now been identified as small clumps of proteins known as oligomers, we have been able to develop a strategy to aim drugs at these toxic particles.”

Alzheimer’s disease leads to the death of nerve cells and tissue loss throughout the brain. Over time, the brain shrinks dramatically and the cell destruction causes memory failure, personality changes, and problems carrying out daily activities.

Scientists identified abnormal deposits called protein oligomers as the most likely suspects of the cause of dementia. Although proteins are normally responsible for important cell processes, when people have Alzheimer’s disease these proteins become rogue, form clumps and kill healthy nerve cells.

“A healthy brain has a quality control system that effectively disposes of potentially dangerous masses of proteins, known as aggregates,” said Vendruscolo. “As we age, the brain becomes less able to get rid of the dangerous deposits, leading to disease. It is like a household recycling system, if you have an efficient system in place then the clutter gets disposed of in a timely manner. If not, over time, you slowly but steadily accumulate junk that you don’t need. It is the same in the brain.”

̽��ֱ��research was carried out by an international team of scientists that also included Professor Sir Christopher Dobson, Master of St John's College, ̽��ֱ�� of Cambridge, at the Centre for Misfolding Diseases (CMD), which he co-founded. “This interdisciplinary study shows that it is possible not just to find compounds that target the toxic oligomers that give rise to neurodegenerative disorders but also to increase their potency in a rational manner,” he said. “It now makes it possible to design molecules that have specific effects on the various stages of disorders such as Alzheimer’s disease, and hopefully to convert them into drugs that can be used in a clinical environment.”

There have been approximately 400 clinical trials for Alzheimer’s disease but none of them has specifically targeted the pathogens that cause it. In the UK, dementia is the only condition in the top 10 causes of death without a treatment to prevent, cure or slow its progression.

“Our research is based on the major conceptual step of identifying protein oligomers as the pathogens and reports a method to systematically develop compounds to target them. This approach enables a new drug discovery strategy,” said Vendruscolo.

̽��ֱ��team believes their first drug candidates could reach clinical trials in around two years. They have co-founded Wren Therapeutics, a biotechnology company based in the newly opened Chemistry of Health building, whose mission is to take the ideas developed at Cambridge and translate them into finding new ways to diagnose and treat Alzheimer’s disease and other misfolding disorders.

̽��ֱ��group’s new strategy is based on a chemical kinetics approach developed in the last ten years by scientists led jointly by Professor Tuomas Knowles, also a Fellow at St John's College, Professor Dobson and Professor Vendruscolo, working at the new centre in Cambridge, in collaboration with scientists at Lund ̽��ֱ�� led by Professor Sara Linse.

“Since the process of aggregation is highly dynamic, the framework of kinetics allows us to approach this problem in a new way and find approaches to stop the generation of toxic proteins species at their very source,” said Knowles.

“This is a detailed academic study looking at how quickly compounds are able to stop amyloid building up into toxic clumps, which are characteristic of Alzheimer’s disease,” said Dr David Reynolds, Chief Scientific Officer from Alzheimer’s Research UK. “With no treatments to slow or stop the diseases that cause dementia, it’s vital we improve approaches like this that could help refine the drug discovery progress and accelerate new treatments for people living with Alzheimer’s.”

Reference:
Sean Chia et al. ‘SAR by kinetics for drug discovery in protein misfolding diseases.’ PNAS (2018). DOI: 10.1073/pnas.1807884115

Adapted from a St John’s College press release.

Researchers have developed a new way to target the toxic particles that destroy healthy brain cells in Alzheimer’s disease.

This is the first time that a systematic method to go after the pathogens – the cause of Alzheimer’s disease - has been proposed.

Michele Vendruscolo

Kateryna Kon

Conceptual image showing blurred brain with loss of neuronal networks

Yes

New research facility for neurodegenerative disorders opened in Cambridge

sc604 — Fri, 21 Sep 2018 10:52:08 +0000

̽��ֱ��building houses the Centre for Misfolding Diseases, a world-leading research facility focused on the misfolding of proteins in human cells - a phenomenon that causes a number of disorders including Alzheimer’s, Parkinson’s, Huntington’s and Motor Neurone Diseases.

̽��ֱ��building has been funded by £17.6 million from Research England’s UK Research Partnership Investment Fund (UKRPIF), as well as with contributions from Elan Pharmaceuticals and AstraZeneca.

Among the philanthropic contributions to the project is a donation of £5 million from Cambridge alumnus Derek Finlay in memory of his wife, Una, who died in May 2016 after a long struggle with Alzheimer’s disease. ̽��ֱ��first-floor laboratory is named the Una Finlay Laboratory in her memory and as the name-plaque was unveiled, Mr Finlay said: “This is a special and very poignant day for myself and my family. This building will enable world-class research that will speed up the search for ways to delay, ameliorate and – I believe – ultimately abolish these dreadful neurodegenerative diseases.”

“ ̽��ֱ��research carried out in this new facility has the potential to affect millions of lives around the world for the better,” said Cambridge Vice-Chancellor Professor Stephen Toope, who opened the building today. “Through collaboration and the sharing of ideas, our research teams will work to find the keys that unlock the mysteries of neurodegenerative disorders, one of the greatest health problems of our age.”

A 2015 report suggested that by 2030, there will be 75 million people worldwide living with Alzheimer’s disease. While the number of cases of Alzheimer’s diseases and other neurodegenerative disorders continues to rise, so too do the costs to society, both economic and emotional.

̽��ֱ��Centre for Misfolding Diseases is co-directed by Professor Sir Christopher Dobson, Professor Tuomas Knowles and Professor Michele Vendruscolo, three world leaders in their fields who have been studying the molecular origins of neurodegenerative diseases.

“This building will for the first time bring together a large number of scientists from different disciplines who are dedicated to establishing the molecular basis of neurodegenerative disorders and to identifying new ways for treating or preventing these debilitating conditions,” said Dobson.

“ ̽��ֱ��treatment of neurodegenerative disorders represents a major challenge, requiring both the development of innovative biophysical approaches and their translation into diagnostic and therapeutic tools,” said Vendruscolo. “With this new building, we have created favourable conditions to combine these two steps.”

“This facility will be a crucial element in helping us to tackle the challenge of understanding the molecular mechanisms of dementia and develop effective ways to counteract them,” said Knowles.

̽��ֱ��new building is also home to a Chemistry of Health Incubator, which will enable closer collaborations between researchers and industry and host spin-out companies in order to increase the rate at which scientific discoveries are translated into new therapies. ̽��ֱ��new incubator is the first in Cambridge to be directly integrated into a ̽��ֱ�� department, and will provide the resources and complementary know-how required to ensure that fundamental research is ultimately used to develop new treatments for patients. ̽��ֱ��first spin-out company to move into the Incubator will be Wren Therapeutics, which is based on a ground-breaking drug discovery method for neurodegenerative disorders developed at the Centre for Misfolding Diseases.

̽��ֱ��Chemistry of Health building, a new facility dedicated to the use of chemical techniques to combat disease, in particular neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases, was officially opened today in Cambridge.

L-R: Vice Chancellor; Derek Finlay; Fiona Finlay; Dame Fiona Reynolds, Master of Emmanuel College; Lord Wilson, former Master of Emmanuel College; and Professor Sir Christopher Dobson

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