AI speeds up drug design for Parkinson’s ten-fold
The researchers, from the University of Cambridge, designed and used an AI-based strategy to identify compounds that block the clumping, or aggregation, of alpha-synuclein, the protein that characterises Parkinson’s.
The team used machine learning techniques to quickly screen a chemical library containing millions of entries, and identified five highly potent compounds for further investigation.
Parkinson’s affects more than six million people worldwide, with that number projected to triple by 2040. No disease-modifying treatments for the condition are currently available. The process of screening large chemical libraries for drug candidates – which needs to happen well before potential treatments can be tested on patients – is enormously time-consuming and expensive, and often unsuccessful.
Using machine learning, the researchers were able to speed up the initial screening process ten-fold, and reduce the cost by a thousand-fold, which could mean that potential treatments for Parkinson’s reach patients much faster. The results are reported in the journal Nature Chemical Biology.
Parkinson’s is the fastest-growing neurological condition worldwide. In the UK, one in 37 people alive today will be diagnosed with Parkinson’s in their lifetime. In addition to motor symptoms, Parkinson’s can also affect the gastrointestinal system, nervous system, sleeping patterns, mood and cognition, and can contribute to a reduced quality of life and significant disability.
Proteins are responsible for important cell processes, but when people have Parkinson’s, these proteins go rogue and cause the death of nerve cells. When proteins misfold, they can form abnormal clusters called Lewy bodies, which build up within brain cells stopping them from functioning properly.
“One route to search for potential treatments for Parkinson’s requires the identification of small molecules that can inhibit the aggregation of alpha-synuclein, which is a protein closely associated with the disease,” said Professor Michele Vendruscolo from the Yusuf Hamied Department of Chemistry, who led the research. “But this is an extremely time-consuming process – just identifying a lead candidate for further testing can take months or even years.”
While there are currently clinical trials for Parkinson’s currently underway, no disease-modifying drug has been approved, reflecting the inability to directly target the molecular species that cause the disease.
This has been a major obstacle in Parkinson’s research, because of the lack of methods to identify the correct molecular targets and engage with them. This technological gap has severely hampered the development of effective treatments.
The Cambridge team developed a machine learning method in which chemical libraries containing millions of compounds are screened to identify small molecules that bind to the amyloid aggregates and block their proliferation.
A small number of top-ranking compounds were then tested experimentally to select the most potent inhibitors of aggregation. The information gained from these experimental assays was fed back into the machine learning model in an iterative manner, so that after a few iterations, highly potent compounds were identified.
“Instead of screening experimentally, we screen computationally,” said Vendruscolo, who is co-Director of the Centre for Misfolding Diseases. “By using the knowledge we gained from the initial screening with our machine learning model, we were able to train the model to identify the specific regions on these small molecules responsible for binding, then we can re-screen and find more potent molecules.”
Using this method, the Cambridge team developed compounds to target pockets on the surfaces of the aggregates, which are responsible for the exponential proliferation of the aggregates themselves. These compounds are hundreds of times more potent, and far cheaper to develop, than previously reported ones.
“Machine learning is having a real impact on drug discovery – it’s speeding up the whole process of identifying the most promising candidates,” said Vendruscolo. “For us, this means we can start work on multiple drug discovery programmes – instead of just one. So much is possible due to the massive reduction in both time and cost – it’s an exciting time.”
The research was conducted in the Chemistry of Health Laboratory in Cambridge, which was established with the support of the UK Research Partnership Investment Fund (UKRPIF) to promote the translation of academic research into clinical programmes.
Reference:
Robert I. Horne et al. ‘Discovery of Potent Inhibitors of α-Synuclein Aggregation Using Structure-Based Iterative Learning.’ Nature Chemical Biology (2024). DOI: 10.1038/s41589-024-01580-x
Researchers have used artificial intelligence techniques to massively accelerate the search for Parkinson’s disease treatments.
Machine learning is having a real impact on drug discovery – it’s speeding up the whole process of identifying the most promising candidatesMichele Vendruscolo Nathan PittMichele Vendruscolo
The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.
Interspecies competition led to even more forms of ancient human – defying evolutionary trends in vertebrates
Climate has long been held responsible for the emergence and extinction of hominin species. In most vertebrates, however, interspecies competition is known to play an important role.
Now, research shows for the first time that competition was fundamental to “speciation” – the rate at which new species emerge – across five million years of hominin evolution.
The study, published today in Nature Ecology & Evolution, also suggests that the species formation pattern of our own lineage was closer to island-dwelling beetles than other mammals.
“We have been ignoring the way competition between species has shaped our own evolutionary tree,” said lead author Dr Laura van Holstein, a University of Cambridge biological anthropologist at Clare College. “The effect of climate on hominin species is only part of the story.”
In other vertebrates, species form to fill ecological “niches” says van Holstein. Take Darwin’s finches: some evolved large beaks for nut-cracking, while others evolved small beaks for feeding on certain insects. When each resource niche gets filled, competition kicks in, so no new finches emerge and extinctions take over.
Van Holstein used Bayesian modelling and phylogenetic analyses to show that, like other vertebrates, most hominin species formed when competition for resources or space were low.
“The pattern we see across many early hominins is similar to all other mammals. Speciation rates increase and then flatline, at which point extinction rates start to increase. This suggests that interspecies competition was a major evolutionary factor.”
However, when van Holstein analysed our own group, Homo, the findings were “bizarre”.
For the Homo lineage that led to modern humans, evolutionary patterns suggest that competition between species actually resulted in the appearance of even more new species – a complete reversal of the trend seen in almost all other vertebrates.
“The more species of Homo there were, the higher the rate of speciation. So when those niches got filled, something drove even more species to emerge. This is almost unparalleled in evolutionary science.”
The closest comparison she could find was in beetle species that live on islands, where contained ecosystems can produce unusual evolutionary trends.
“The patterns of evolution we see across species of Homo that led directly to modern humans is closer to those of island-dwelling beetles than other primates, or even any other mammal.”
Recent decades have seen the discovery of several new hominin species, from Australopithecus sediba to Homo floresiensis. Van Holstein created a new database of “occurrences” in the hominin fossil record: each time an example of a species was found and dated, around 385 in total.
Fossils can be an unreliable measure of species’ lifetimes. “The earliest fossil we find will not be the earliest members of a species,” said van Holstein.
“How well an organism fossilises depends on geology, and on climatic conditions: whether it is hot or dry or damp. With research efforts concentrated in certain parts of the world, and we might well have missed younger or older fossils of a species as a result.”
Van Holstein used data modelling to address this problem, and factor in likely numbers of each species at the beginning and end of their existence, as well as environmental factors on fossilisation, to generate new start and end dates for most known hominin species (17 in total).
She found that some species thought to have evolved through “anagenesis” – when one slowly turns into another, but lineage doesn’t split – may have actually “budded”: when a new species branches off from an existing one.*
This meant that several more hominin species than previously assumed were co-existing, and so possibly competing.
While early species of hominins, such as Paranthropus, probably evolved physiologically to expand their niche – adapting teeth to exploit new types of food, for example – the driver of the very different pattern in our own genus Homo may well have been technology.
“Adoption of stone tools or fire, or intensive hunting techniques, are extremely flexible behaviours. A species that can harness them can quickly carve out new niches, and doesn’t have to survive vast tracts of time while evolving new body plans,” said van Holstein
She argues that an ability to use technology to generalise, and rapidly go beyond ecological niches that force other species to compete for habitat and resources, may be behind the exponential increase in the number of Homo species detected by the latest study.
But it also led to Homo sapiens – the ultimate generalisers. And competition with an extremely flexible generalist in almost every ecological niche may be what contributed to the extinction of all other Homo species.
Added van Holstein: “These results show that, although it has been conventionally ignored, competition played an important role in human evolution overall. Perhaps most interestingly, in our own genus it played a role unlike that across any other vertebrate lineage known so far.”
Competition between species played a major role in the rise and fall of hominins, and produced a “bizarre” evolutionary pattern for the Homo lineage.
This is almost unparalleled in evolutionary scienceLaura van HolsteinThe Duckworth LaboratoryA cast of the skull of Homo Heidelbergensis, one of the hominin species analysed in the latest study.
The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.
Wed 24 Apr 17:00: Molecular Mechanism of T-cell Exhaustion
This Cambridge Immunology and Medicine Seminar will take place on Wednesday 24th April 2024, starting at 5:00 pm.
Location: Max Perutz Lecture Theatre, Francis Crick Avenue, MRC Laboratory of Molecular Biology (LMB), Cambridge
Speaker: Prof John Wherry; Chair, Department of Systems Pharmacology & Translational Therapeutics Richard and Barbara Schiffrin President’s Distinguished Professor Director, Institute for Immunology Co-Program Leader, Immunobiology Program, Abramson Cancer Center Co-Director, Parker Institute for Cancer Immunotherapy. University of Pennsylvania
Title: Molecular Mechanism of T-cell Exhaustion
Host: Professor Menna Clatworthy, Director of CITIID , NIHR Research Professor and Professor of Translational Immunology, University of Cambridge
Refreshments will be available following the Seminar.
- Speaker: Professor John Wherry, Director, Institute for Immunology, University of Pennsylvania
- Wednesday 24 April 2024, 17:00-18:00
- Venue: Max Perutz Lecture Theatre, MRC LMB, Francis Crick Avenue, Cambridge CB2 0QH .
- Series: Immunology and Medicine Seminars; organiser: Ruth Paton.
Wed 24 Apr 17:00: Molecular Mechanism of T-cell Exhaustion
This Cambridge Immunology and Medicine Seminar will take place on Wednesday 24th April 2024, starting at 5:00 pm.
Location: Max Perutz Lecture Theatre, Francis Crick Avenue, MRC Laboratory of Molecular Biology (LMB), Cambridge
Speaker: Prof John Wherry; Chair, Department of Systems Pharmacology & Translational Therapeutics Richard and Barbara Schiffrin President’s Distinguished Professor Director, Institute for Immunology Co-Program Leader, Immunobiology Program, Abramson Cancer Center Co-Director, Parker Institute for Cancer Immunotherapy. University of Pennsylvania
Title: Molecular Mechanism of T-cell Exhaustion
Host: Professor Menna Clatworthy, Director of CITIID , NIHR Research Professor and Professor of Translational Immunology, University of Cambridge
Refreshments will be available following the Seminar.
- Speaker: Professor John Wherry, Director, Institute for Immunology, University of Pennsylvania
- Wednesday 24 April 2024, 17:00-18:00
- Venue: Max Perutz Lecture Theatre, MRC LMB, Francis Crick Avenue, Cambridge CB2 0QH .
- Series: Immunology and Medicine Seminars; organiser: Ruth Paton.
Wed 15 May 16:00: How use of SSRI impacts placenta and mammary gland development Contact Fiona Roby for zoom link
Selective serotonin reuptake inhibitors (SSRI) are the most commonly prescribed drug class in the US. Untreated depression during pregnancy creates a risk for maternal wellbeing and is coupled with adverse pregnancy outcomes with causes that are poorly understood and use of SSRI among pregnant women is increasing. Fluoxetine (Prozac) and sertraline (Zoloft) are the most prescribed medications for pregnant women in their first trimester. With nearly one in five women experiencing depression, SSRI use during pregnancy continues to increase in the US. Antenatal SSRI use has been demonstrated to also result in increased neonatal mortality and morbidity. Therefore, presenting a conundrum for medical care providers when making decisions as to how to treat pregnant women with depression and also protect the pregnancy, and health outcomes for the infant. Importantly, and often under looked, is that SSRI not only impact the neuronal serotonin transporter (SERT), but they also impact the effects of SERT throughout the body. Our work has recently demonstrated that treatment with fluoxetine prepartum results increased death of offspring and increased morbidity for the offspring that survive, which we have recapitulated in a sheep model. Further, our work demonstrates the SSRI also impact both mammary gland function and development, as well as maternal outcomes, recently demonstrating that use of fluoxetine increases adiposity in offspring up to 12 weeks of age, and that male offspring appear to be disproportionally affected. We continue to investigate the impact of SSRI use on the placenta, mammary gland development, and long-term effects on both dam and offspring. Our goal is to develop novel interventions that will allow the dam to continue SSRI treatment if needed that will not impact her long-term health, as well as the long-term health of the offspring.
Contact Fiona Roby for zoom link
- Speaker: Laura L. Hernandez, Department of Animal and Dairy Sciences University of Wisconsin-Madison
- Wednesday 15 May 2024, 16:00-17:00
- Venue: by zoom.
- Series: Departmental Seminar Programme, Department of Veterinary Medicine; organiser: Fiona Roby.
Wed 15 May 16:00: How use of SSRI impacts placenta and mammary gland development Contact Fiona Roby for zoom link
Selective serotonin reuptake inhibitors (SSRI) are the most commonly prescribed drug class in the US. Untreated depression during pregnancy creates a risk for maternal wellbeing and is coupled with adverse pregnancy outcomes with causes that are poorly understood and use of SSRI among pregnant women is increasing. Fluoxetine (Prozac) and sertraline (Zoloft) are the most prescribed medications for pregnant women in their first trimester. With nearly one in five women experiencing depression, SSRI use during pregnancy continues to increase in the US. Antenatal SSRI use has been demonstrated to also result in increased neonatal mortality and morbidity. Therefore, presenting a conundrum for medical care providers when making decisions as to how to treat pregnant women with depression and also protect the pregnancy, and health outcomes for the infant. Importantly, and often under looked, is that SSRI not only impact the neuronal serotonin transporter (SERT), but they also impact the effects of SERT throughout the body. Our work has recently demonstrated that treatment with fluoxetine prepartum results increased death of offspring and increased morbidity for the offspring that survive, which we have recapitulated in a sheep model. Further, our work demonstrates the SSRI also impact both mammary gland function and development, as well as maternal outcomes, recently demonstrating that use of fluoxetine increases adiposity in offspring up to 12 weeks of age, and that male offspring appear to be disproportionally affected. We continue to investigate the impact of SSRI use on the placenta, mammary gland development, and long-term effects on both dam and offspring. Our goal is to develop novel interventions that will allow the dam to continue SSRI treatment if needed that will not impact her long-term health, as well as the long-term health of the offspring.
Contact Fiona Roby for zoom link
- Speaker: Laura L. Hernandez, Department of Animal and Dairy Sciences University of Wisconsin-Madison
- Wednesday 15 May 2024, 16:00-17:00
- Venue: by zoom.
- Series: Departmental Seminar Programme, Department of Veterinary Medicine; organiser: Fiona Roby.
Is Democracy Dying?
2024 is the year of elections. A record number of elections will take place, with half the adult population of the world, some two billion people, having the chance to vote. Is this a milestone to be celebrated in our democratic history or are we at a crossroads where the fate of liberal democracy hangs in the balance?
Against a backdrop of polarising populist movements, the erosion of trust in traditional institutions and a decline of democratic norms, we ask: is democracy dying? Is the election of populists an expression of democracy or a breakdown of democracy? How resilient are our democratic institutions in the face of unprecedented challenges? Is the tension between liberal and democracy ultimately too great to resolve?
Join us on 24 April to grapple with these questions in our second Vice-Chancellor’s Dialogues, hosted by Vice-Chancellor Professor Deborah Prentice.
Our speakers- David Goodhart, founding editor of Prospect magazine and Head of the Demography, Immigration and Integration unit at the think tank Policy Exchange. He is the author of The Road to Somewhere: The Populist Revolt and the Future of Politics.
- Nabila Ramdani, award-winning journalist, broadcaster and academic. She is the author of Fixing France: How to Repair a Broken Republic.
- Helen Thompson, Professor of Political Economy at the University of Cambridge. She is a regular panellist on Talking Politics and a columnist for the New Statesman.
The discussion will be chaired by Roger Mosey, Master of Selwyn College and former Editorial Director of the BBC. The event is public and open to all, but attendees must register on Eventbrite.
If you're not able to attend, we'll publish a recording of the event in the coming weeks.
The second Vice-Chancellor’s Dialogues event grapples with the question: 'is liberal democracy dying?' The evening will be hosted by Vice-Chancellor Professor Deborah Prentice and chaired by the Master of Selwyn College.
The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.
Wed 15 May 16:00: How use of SSRI impacts placenta and mammary gland development
Selective serotonin reuptake inhibitors (SSRI) are the most commonly prescribed drug class in the US. Untreated depression during pregnancy creates a risk for maternal wellbeing and is coupled with adverse pregnancy outcomes with causes that are poorly understood and use of SSRI among pregnant women is increasing. Fluoxetine (Prozac) and sertraline (Zoloft) are the most prescribed medications for pregnant women in their first trimester. With nearly one in five women experiencing depression, SSRI use during pregnancy continues to increase in the US. Antenatal SSRI use has been demonstrated to also result in increased neonatal mortality and morbidity. Therefore, presenting a conundrum for medical care providers when making decisions as to how to treat pregnant women with depression and also protect the pregnancy, and health outcomes for the infant. Importantly, and often under looked, is that SSRI not only impact the neuronal serotonin transporter (SERT), but they also impact the effects of SERT throughout the body. Our work has recently demonstrated that treatment with fluoxetine prepartum results increased death of offspring and increased morbidity for the offspring that survive, which we have recapitulated in a sheep model. Further, our work demonstrates the SSRI also impact both mammary gland function and development, as well as maternal outcomes, recently demonstrating that use of fluoxetine increases adiposity in offspring up to 12 weeks of age, and that male offspring appear to be disproportionally affected. We continue to investigate the impact of SSRI use on the placenta, mammary gland development, and long-term effects on both dam and offspring. Our goal is to develop novel interventions that will allow the dam to continue SSRI treatment if needed that will not impact her long-term health, as well as the long-term health of the offspring.
- Speaker: Laura L. Hernandez, Department of Animal and Dairy Sciences University of Wisconsin-Madison
- Wednesday 15 May 2024, 16:00-17:00
- Venue: LT2.
- Series: Departmental Seminar Programme, Department of Veterinary Medicine; organiser: Fiona Roby.
Wed 15 May 16:00: How use of SSRI impacts placenta and mammary gland development
Selective serotonin reuptake inhibitors (SSRI) are the most commonly prescribed drug class in the US. Untreated depression during pregnancy creates a risk for maternal wellbeing and is coupled with adverse pregnancy outcomes with causes that are poorly understood and use of SSRI among pregnant women is increasing. Fluoxetine (Prozac) and sertraline (Zoloft) are the most prescribed medications for pregnant women in their first trimester. With nearly one in five women experiencing depression, SSRI use during pregnancy continues to increase in the US. Antenatal SSRI use has been demonstrated to also result in increased neonatal mortality and morbidity. Therefore, presenting a conundrum for medical care providers when making decisions as to how to treat pregnant women with depression and also protect the pregnancy, and health outcomes for the infant. Importantly, and often under looked, is that SSRI not only impact the neuronal serotonin transporter (SERT), but they also impact the effects of SERT throughout the body. Our work has recently demonstrated that treatment with fluoxetine prepartum results increased death of offspring and increased morbidity for the offspring that survive, which we have recapitulated in a sheep model. Further, our work demonstrates the SSRI also impact both mammary gland function and development, as well as maternal outcomes, recently demonstrating that use of fluoxetine increases adiposity in offspring up to 12 weeks of age, and that male offspring appear to be disproportionally affected. We continue to investigate the impact of SSRI use on the placenta, mammary gland development, and long-term effects on both dam and offspring. Our goal is to develop novel interventions that will allow the dam to continue SSRI treatment if needed that will not impact her long-term health, as well as the long-term health of the offspring.
- Speaker: Laura L. Hernandez, Department of Animal and Dairy Sciences University of Wisconsin-Madison
- Wednesday 15 May 2024, 16:00-17:00
- Venue: LT2.
- Series: Departmental Seminar Programme, Department of Veterinary Medicine; organiser: Fiona Roby.
Low-Density TaqMan® Array Cards for the Detection of Pathogens
Methods Microbiol. 2015;42:199-218. doi: 10.1016/bs.mim.2015.06.002. Epub 2015 Aug 3.
ABSTRACT
Real-time PCR assays have revolutionised diagnostic microbiology over the past 15 years or more. Adaptations and improvements over that time frame have led to the development of multiplex assays. However, limitations in terms of available fluorophores has meant the number of assays which can be combined has remained in single figures. This latter limitation has led to the focus tending to be on individual pathogens and their detection. This chapter describes the development of TaqMan® Array Cards (TACs), technology which allows the detection of multiple pathogens (up to 48 targets) from a single nucleic acid extract, utilising small volumes and real-time PCR. This in turn lends itself to a syndromic approach to infectious disease diagnosis. Using the examples of TACs we have developed in our own laboratory, as well as others, we explain the design, optimisation and use of TACs for respiratory, gastrointestinal and liver infections. Refinement of individual assays is discussed as well as the incorporation of appropriate internal and process controls onto the array cards. Finally, specific examples are given of instances where the assays have had a direct, positive impact on patient care.
PMID:38620215 | PMC:PMC7172410 | DOI:10.1016/bs.mim.2015.06.002
A lineage-specific protein network at the trypanosome nuclear envelope
Nucleus. 2024 Dec;15(1):2310452. doi: 10.1080/19491034.2024.2310452. Epub 2024 Apr 11.
ABSTRACT
The nuclear envelope (NE) separates translation and transcription and is the location of multiple functions, including chromatin organization and nucleocytoplasmic transport. The molecular basis for many of these functions have diverged between eukaryotic lineages. Trypanosoma brucei, a member of the early branching eukaryotic lineage Discoba, highlights many of these, including a distinct lamina and kinetochore composition. Here, we describe a cohort of proteins interacting with both the lamina and NPC, which we term lamina-associated proteins (LAPs). LAPs represent a diverse group of proteins, including two candidate NPC-anchoring pore membrane proteins (POMs) with architecture conserved with S. cerevisiae and H. sapiens, and additional peripheral components of the NPC. While many of the LAPs are Kinetoplastid specific, we also identified broadly conserved proteins, indicating an amalgam of divergence and conservation within the trypanosome NE proteome, highlighting the diversity of nuclear biology across the eukaryotes, increasing our understanding of eukaryotic and NPC evolution.
PMID:38605598 | DOI:10.1080/19491034.2024.2310452
Study unpicks why childhood maltreatment continues to impact on mental and physical health into adulthood
Individuals who experienced maltreatment in childhood – such as emotional, physical and sexual abuse, or emotional and physical neglect – are more likely to develop mental illness throughout their entire life, but it is not yet well understood why this risk persists many decades after maltreatment first took place.
In a study published in Proceedings of the National Academy of Sciences, scientists from the University of Cambridge and Leiden University found that adult brains continue to be affected by childhood maltreatment in adulthood because these experiences make individuals more likely to experience obesity, inflammation and traumatic events, all of which are risk factors for poor health and wellbeing, which in turn also affect brain structure and therefore brain health.
The researchers examined MRI brain scans from approximately 21,000 adult participants aged 40 to 70 years in UK Biobank, as well as information on body mass index (an indicator of metabolic health), CRP (a blood marker of inflammation) and experiences of childhood maltreatment and adult trauma.
Sofia Orellana, a PhD student at the Department of Psychiatry and Darwin College, University of Cambridge, said: “We’ve known for some time that people who experience abuse or neglect as a child can continue to experience mental health problems long into adulthood and that their experiences can also cause long term problems for the brain, the immune system and the metabolic system, which ultimately controls the health of your heart or your propensity to diabetes for instance. What hasn’t been clear is how all these effects interact or reinforce each other.”
Using a type of statistical modelling that allowed them to determine how these interactions work, the researchers confirmed that experiencing childhood maltreatment made individuals more likely to have an increased body mass index (or obesity) and experience greater rates of trauma in adulthood. Individuals with a history of maltreatment tended to show signs of dysfunction in their immune systems, and the researchers showed that this dysfunction is the product of obesity and repeated exposure to traumatic events.
Next, the researchers expanded their models to include MRI measures of the adult’s brains and were able to show that widespread increases and decreases in brain thickness and volume associated with greater body mass index, inflammation and trauma were attributable to childhood maltreatment having made these factors more likely in the first place. These changes in brain structure likely mean that some form of physical damage is occurring to brain cells, affecting how they work and function.
Although there is more to do to understand how these effects operate at a cellular level in the brain, the researchers believe that their findings advance our understanding of how adverse events in childhood can contribute to life-long increased risk of brain and mind health disorders.
Professor Ed Bullmore from the Department of Psychiatry and an Honorary Fellow at Downing College, Cambridge, said: “Now that we have a better understanding of why childhood maltreatment has long term effects, we can potentially look for biomarkers – biological red flags – that indicate whether an individual is at increased risk of continuing problems. This could help us target early on those who most need help, and hopefully aid them in breaking this chain of ill health.”
The research was supported by MQ: Transforming Mental Health, the Royal Society, Medical Research Council, National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre, the NIHR Applied Research Collaboration East of England, Girton College and Darwin College.
Reference
Orellana, SC et al. Childhood maltreatment influences adult brain structure through its effects on immune, metabolic and psychosocial factors. PNAS; 9 Apr 2024 ; DOI: 10.1073/pnas.230470412
Childhood maltreatment can continue to have an impact long into adulthood because of how it effects an individual’s risk of poor physical health and traumatic experiences many years later, a new study has found.
We’ve known for some time that people who experience abuse or neglect as a child can continue to experience mental health problems long into adulthoodSofia Orellanamali desha (Unsplash)Black and white image of boy curled up on the floor
The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.
Four Cambridge researchers awarded prestigious European Research Council Advanced Grants
The European Research Council (ERC) has announced today the award of 255 Advanced Grants to outstanding research leaders across Europe, as part of the EU’s Horizon Europe programme. Four University of Cambridge researchers are amongst those to receive this prestigious and competitive funding.
The University of Cambridge’s grant awardees are:
Dr Albert Guillén i Fàbregas in the Department of Engineering for his project Scaling and Concentration Laws in Information Theory.
Fàbregas, who has previously received ERC Starting, Consolidator and Proof of Concept Grants, said: “I am truly delighted with the news that the ERC will continue to fund my research in information theory, which studies the mathematical aspects of data transmission and data compression.
“This project will broaden the theory to study arbitrary scaling laws of the number of messages to transmit or compress."
Professor Beverley Glover in the Department of Plant Sciences and Director of Cambridge University Botanic Garden, for her project Convergent evolution of floral patterning through alternative optimisation of mechanical parameter space.
Glover said: “This funding will enable us to explore how iridescent colour evolved repeatedly in different flowers. We think it will shed new light on evolution itself, as we think about the development of iridescence structure from a mechanical perspective, focusing on the forces acting as a petal grows and the mechanical properties of the petal tissue.
“It's only possible for me to do this work because of the amazing living collection at Cambridge University Botanic Garden, and I'm thrilled that the ERC is keen to support it."
Professor Ian Henderson in the Department of Plant Sciences for his project Evolution of the Arabidopsis Pancentromere.
Henderson said: “This project seeks to investigate enigmatic regions of the genome called the centromeres, using the model plant Arabidopsis. These regions play a deeply conserved role in cell division yet paradoxically are fast evolving.
“I am highly honoured and excited to be awarded an ERC Advanced grant. The advent of long-read sequencing technology makes addressing these questions timely. The ERC’s long-term support will allow us to capitalise on these advances, build new collaborations, and train postdoctoral researchers.”
Professor Paul Lane in the Department of Archaeology, for his project Landscape Historical Ecology and Archaeology of Ancient Pastoral Societies in Kenya.
Lane said: “Pastoralism has been an extraordinarily resilient livelihood strategy across Africa. This project provides an excellent opportunity to reconstruct how East Africa’s pastoralists responded to significant climate change in the past, and to draw lessons from these adaptations for responding to contemporary climate crises in a region that is witnessing heightened water scarcity and loss of access to critically important grazing lands.”
“This project will allow us to utilise the department’s world-leading archaeological science laboratories and expertise to answer crucial questions about past patterns of mobility, dietary diversity, climatic regimes and food security among East African pastoralists over the last fifteen hundred years. This has never been attempted before for this time period.”
Professor Anne Ferguson-Smith, Pro-Vice Chancellor for Research at the University of Cambridge said: “Many congratulations to Albert, Beverley, Ian and Paul on receiving these prestigious and highly competitive awards. It is fantastic that their ambitious, cutting-edge research will be supported by the European Research Council, marking them as outstanding European research leaders.
“Now that the UK is an associated country to Horizon Europe I encourage other Cambridge researchers to also consider applying to the ERC and other Horizon Europe programmes.”
President of the European Research Council Professor Maria Leptin said: “Congratulations to the 255 researchers who will receive grants to follow their scientific instinct in this new funding round. I am particularly happy to see more mid-career scientists amongst the Advanced Grant winners this time. I hope that it will encourage more researchers at this career stage to apply for these grants.”
The ERC is the premier European funding organisation for excellent frontier research. The 255 ERC Advanced Grants, totalling €652 million, support cutting-edge research in a wide range of fields from medicine and physics to social sciences and humanities.
The European Commission and the UK Government have reached an agreement on the association of the UK to Horizon Europe, which applies for calls for proposals implementing the 2024 budget and onwards.
The ERC Advanced Grants target established, leading researchers with a proven track-record of significant achievements. In recent years, there has been a steady rise in mid-career researchers (12-17 years post-PhD), who have been successful in the Advanced Grants competitions, with 18% securing grants in this latest round.
The funding provides leading senior researchers with the opportunity to pursue ambitious, curiosity-driven projects that could lead to major scientific breakthroughs.
Many congratulations to Albert, Beverley, Ian and Paul... It is fantastic that their ambitious, cutting-edge research will be supported by the European Research Council, marking them as outstanding European research leaders.Anne Ferguson-Smith
The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.
Trade-offs in the externalities of pig production are not inevitable
Nat Food. 2024 Apr 11. doi: 10.1038/s43016-024-00921-2. Online ahead of print.
ABSTRACT
Farming externalities are believed to co-vary negatively, yet trade-offs have rarely been quantified systematically. Here we present data from UK and Brazilian pig production systems representative of most commercial systems across the world ranging from 'intensive' indoor systems through to extensive free range, Organic and woodland systems to explore co-variation among four major externality costs. We found that no specific farming type was consistently associated with good performance across all domains. Generally, systems with low land use have low greenhouse gas emissions but high antimicrobial use and poor animal welfare, and vice versa. Some individual systems performed well in all domains but were not exclusive to any particular type of farming system. Our findings suggest that trade-offs may be avoidable if mitigation focuses on lowering impacts within system types rather than simply changing types of farming.
PMID:38605128 | DOI:10.1038/s43016-024-00921-2
Differential effects of weather, plant phenology and predators on the seasonal variation of aphids on cabbage
J Appl Entomol. 2023 May;147(4):261-270. doi: 10.1111/jen.13106. Epub 2023 Feb 6.
ABSTRACT
The aphids Lipaphis erysimi pseudobrassicae (Davis) and Myzus persicae (Sulzer) pose serious threats to the production of cruciferous crops in the tropics. Understanding their population dynamics is important for developing integrated pest management programmes to minimize their damage to crops. This study investigated the effects of climatic factors, natural enemies and plant age on the population dynamics of these pests. The population density of aphids and their natural enemies in 20 cabbage plants, and weather conditions were monitored for five cropping seasons from 2019 to 2021 in two agroecological zones of Ghana (Coastal Savannah and Deciduous Forest zones). The highest population density of L. e pseudobrassicae was recorded in January (dry season) in both agroecological zones, while the highest population density for M. persicae occurred in September (minor rainy season) and August (dry spell) in the Coastal Savannah and Deciduous Forest zones, respectively. The highest aphid densities were noted to occur during periods with low relative humidity and low rainfall. The population density of L. e. pseudobrassicae was significantly negatively related to plant age, air temperature and relative humidity, and positively related to syrphids (Paragus borbonicus) and spiders in the Coastal Savannah zone, while in the Deciduous Forest zone, it was significantly positively related to coccinellids. On the other hand, M. persicae population density was significantly positively related to syrphids and coccinellids in the Deciduous Forest zone. Rainfall negatively affected syrphids in the Coastal Savannah zone, while air temperature positively affected syrphids and negatively affected spiders in the Deciduous Forest zone. Coccinellids had a significant positive relationship with relative humidity in the Deciduous Forest zone. This study provides important insights into the key factors that regulate aphid population densities on cabbage and will support development of timely interventions to manage these pests.
PMID:38601126 | PMC:PMC11005107 | DOI:10.1111/jen.13106
Pork labelling schemes ‘not helpful’ in making informed buying choices, say researchers
Researchers have evaluated different types of pig farming – including woodland, organic, free range, RSPCA assured, and Red Tractor certified, to assess each systems’ impact across four areas: land use (representing biodiversity loss), greenhouse gas emissions, antibiotics use and animal welfare. Their study concludes that none of the farm types performed consistently well across all four areas – a finding that has important implications for increasingly climate conscious consumers, as well as farmers themselves.
However, there were individual farms that did perform well in all domains, including an indoor Red Tractor farm, an outdoor bred, indoor finished RSPCA assured farm and fully outdoor woodland farm. “Outliers like these show that trade-offs are not inevitable,” said lead author Dr Harriet Bartlett, Research Associate at the University of Oxford's Smith School of Enterprise and the Environment, who was formerly at the University of Cambridge.
“Somewhat unexpectedly we found that a handful of farms perform far better than average across all four of our environmental and welfare measures,” added senior author Andrew Balmford, Professor of Conservation Science at the University of Cambridge. However, none of the current label or assurance schemes predicted which farms these would be.
“The way we classify farm types and label pork isn’t helpful for making informed decisions when it comes to buying more sustainable meat. Even more importantly, we aren’t rewarding and incentivising the best-performing farmers. Instead of focusing on farm types or practices, we need to focus on meaningful outcomes for people, the planet and the pigs – and assess, and reward farms based on these,” said Bartlett.
The findings also show that common assumptions around food labelling can be misplaced. For instance, Organic farming systems, which consumers might see as climate and environmentally friendly, have on average three times the CO2 output per kg of meat of more intensive Red Tractor or RSPCA assured systems and four times the land use. However, these same systems use on average almost 90% fewer antibiotic medicines, and result in improved animal welfare compared with production from Red tractor or RSPCA assured systems.
The way we classify livestock farms must be improved, Bartlett says, because livestock production is growing rapidly, especially pork production, which has quadrupled in the past 50 years and already accounts for 9% of greenhouse gas emissions from livestock. Pig farming also uses more antibiotics than any other livestock sector, and 8.5% of all arable land.
“Our findings show that mitigating the environmental impacts of livestock farming isn’t a case of saying which farm type is the best,” said Bartlett. “There is substantial scope for improvement within types, and our current means of classification is not identifying the best farms for the planet and animals overall. Instead, we need to identify farms that successfully limit their impacts across all areas of societal concern, and understand, promote and incentivise their practises.”
The study reached its conclusions using data from 74 UK and 17 Brazilian breed-to-finish systems, each made up of 1-3 farms and representing the annual production of over 1.2 million pigs. It is published today in the journal Nature Food.
“To the best of our knowledge, our dataset covers by far the largest and most diverse sample of pig production systems examined in any single study,” said Bartlett.
James Wood, Professor of Equine and Farm Animal Science at the University of Cambridge, commented: “This important study identifies a key need to clarify what different farm labels should indicate to consumers; there is a pressing need to extend this work into other farming sectors. It also clearly demonstrates the critical importance that individual farmers play in promoting best practice across all farming systems.”
Trade-offs in the externalities of pig production are not inevitable was authored by academics at the University of Oxford, University of Cambridge and the University of São Paulo.
The research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC).
Reference: Bartlett, H.,‘Trade-offs in the externalities of pig production are not inevitable.’ Nature Food, April 2024. DOI: 10.1038/s43016-024-00921-2
Adapted from a press release by the University of Oxford.
Farmers don’t have to choose between lowering environmental impact and improving welfare for their pigs, a new study has found: it is possible to do both. But this is not reflected in the current food labelling schemes relied on by consumers.
The way we classify farm types and label pork isn’t helpful for making informed decisions when it comes to buying more sustainable meat.Harriet BartlettCharity Burggraaf/ GettyTwo pigs on a farm
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Wed 24 Apr 17:00: Molecular Mechanism of T-cell Exhaustion
This Cambridge Immunology and Medicine Seminar will take place on Wednesday 24th April 2024, starting at 5:00 pm.
Speaker: Prof John Wherry; Chair, Department of Systems Pharmacology & Translational Therapeutics Richard and Barbara Schiffrin President’s Distinguished Professor Director, Institute for Immunology Co-Program Leader, Immunobiology Program, Abramson Cancer Center Co-Director, Parker Institute for Cancer Immunotherapy. University of Pennsylvania
Title: Molecular Mechanism of T-cell Exhaustion
Host: Professor Menna Clatworthy, Director of CITIID , NIHR Research Professor and Professor of Translational Immunology, University of Cambridge
Refreshments will be available following the Seminar.
- Speaker: Professor John Wherry, Director, Institute for Immunology, University of Pennsylvania
- Wednesday 24 April 2024, 17:00-18:00
- Venue: LMB lecture theatre, Francis Crick Avenue, CB2 0QH Cambridge.
- Series: Immunology and Medicine Seminars; organiser: Ruth Paton.
Wed 24 Apr 17:00: Molecular Mechanism of T-cell Exhaustion
This Cambridge Immunology and Medicine Seminar will take place on Wednesday 24th April 2024, starting at 5:00 pm.
Speaker: Prof John Wherry; Chair, Department of Systems Pharmacology & Translational Therapeutics Richard and Barbara Schiffrin President’s Distinguished Professor Director, Institute for Immunology Co-Program Leader, Immunobiology Program, Abramson Cancer Center Co-Director, Parker Institute for Cancer Immunotherapy. University of Pennsylvania
Title: Molecular Mechanism of T-cell Exhaustion
Host: Professor Menna Clatworthy, Director of CITIID , NIHR Research Professor and Professor of Translational Immunology, University of Cambridge
Refreshments will be available following the Seminar.
- Speaker: Professor John Wherry, Director, Institute for Immunology, University of Pennsylvania
- Wednesday 24 April 2024, 17:00-18:00
- Venue: LMB lecture theatre, Francis Crick Avenue, CB2 0QH Cambridge.
- Series: Immunology and Medicine Seminars; organiser: Ruth Paton.
Collections-based research and innovation receives vital investment from Research England
The University cares for the country’s highest concentration of internationally important collections outside London, with more than five million works of art, artefacts and specimens. Together, these collections play a fundamental role in delivering the University mission to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence and encompasses collaboration with and support of world-renowned researchers, game-changing research-led exhibitions and wide-ranging inclusion and learning programmes, promoting wellbeing, creativity and connectivity.
“I’m delighted that Research England has made such a strong statement of support for collections-based research at Cambridge, particularly in a challenging funding landscape,” said Kamal Munir, Pro-Vice-Chancellor for University Community and Engagement.
“The University continues to invest in enhanced research infrastructure and services to generate and enable research that spans the arts and the sciences, including via a Strategic Research Initiative, Collections-Connections-Communities that provides a convening space for research that benefits our communities. HEMG funding is critical in ensuring our collections support researchers and students across the UK and worldwide, through infrastructure, services, staffing and equitable collaboration.”
This year, the University Herbarium joins the portfolio for the first time and the Sedgwick Museum of Earth Sciences rejoins the portfolio.
Sam Brockington, academic lead for the Herbarium, which was recently awarded Designated status, said: “It’s fantastic to see the University Herbarium receive investment in this way. The Herbarium is the fourth-largest of its kind in the country, and a rich resource that supports a huge range of scientific and humanities research. Research supported by the Herbarium ranges from the discovery of species new to science, to the genomics of crop improvement, and investigations into the history and development of scientific ideas and natural history. This investment will enable us to substantially develop our support for the wider academic community.”
Dr Liz Hide, Director of the Sedgwick Museum of Earth Sciences, which has been awarded £210,000 a year, said: “I’m delighted that Research England has recognised the strength of the Sedgwick’s collections and their importance to the UK and international research landscape. Over the next five years, this new investment will be transformative for the Sedgwick Museum, ensuring researchers can fully utilise our new Collections Research Centre, and enabling our outstanding collections to inspire many new avenues of research across both the sciences and the humanities.”
Dr Juliette Fritsch, the University’s first Director for Collections’ Strategy, said: "I’m thrilled to work across the incredible resources contained within the University’s museums, libraries, and botanic garden collections to create strategies together, building on major initiatives, such as the cross-collections Power and Memory programme. These integrated approaches enhance our collective impact and are only possible through the input of our funders, including Research England and Arts Council England.”
The full list of University of Cambridge museums and collections awarded HEMG funding are:
1. Cambridge University Botanic Garden
2. Fitzwilliam Museum
3. Kettle’s Yard
4. Museum of Archaeology & Anthropology (MAA)
5. University Museum of Zoology
6. Polar Museum
7. Whipple Museum of the History of Science
8. Sedgwick Museum of Earth Sciences
9. Cambridge University Herbarium
Research England has supported nine of the University’s museums and collections with £3m a year of Higher Education Museums, Galleries and Collections (HEMG) funding, over the coming five years.
HEMG funding is critical in ensuring our collections support researchers and students across the UK and worldwideKamal Munir©markbox.co.ukRhododendron brookianum type specimen from the University of Cambridge Herbarium
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£9.2m boost for next generation of Cambridge cancer experts
The charity is to award the funding over the next five years to train early-career clinician scientists – doctors who also carry out medical research - as part of its Clinical Academic Training Programme.
The Clinical Academic Training Programme will invest £58.7m at nine research centres including the Cancer Research UK Cambridge Centre in partnership with the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, which includes Addenbrooke’s Hospital.
Clinician scientists play an essential role in translating cancer research, helping to bridge the gap between scientific research carried out in laboratories and clinical research involving patients.
Dr Caroline Watson – now a Group Leader in the Early Cancer Institute at the University of Cambridge and Honorary Haematology Consultant at Addenbrooke’s Hospital – has benefited from this funding, having previously been awarded a three-year Cancer Research UK Clinical Research Training Fellowship in 2017. Caroline was first author on a Science paper and Nature Genetics paper, based on her Cancer Research UK-funded research, that identified which mutations in healthy blood are associated with the highest risk of developing blood cancer.
Dr Watson said: “As we age, we all acquire mutations in the cells that make up our tissues. The vast majority are harmless, but some can increase cancer risk. With blood’s relative ease of sampling and improved DNA sequencing costs, we now have enough data, across many thousands of individuals, to determine which specific mutations enable cells to expand most rapidly and could therefore confer the highest risk of cancer. Knowing whether specific mutations are high-risk or clinically insignificant is key for the future of personalised cancer risk.
“I’m immensely grateful for the funding I received from Cancer Research UK, which provided me with a key stepping stone in my clinician scientist career. I feel fortunate to now be able to spend the bulk of my time focused on research, but also continue with some clinical work in parallel. Having been involved in setting up the UK’s first clinic focused on blood cancer prevention at Addenbrooke’s Hospital, I look forward to translating my research findings to directly benefit patients.”
Michelle Mitchell, Cancer Research UK’s Chief Executive, said: “Clinician scientists have a very important role to play by bringing their knowledge and experience of treating people with cancer to scientific research.
“We need all our doctors and scientists to be able to reach their full potential, no matter their background. That’s why we are continuing to provide flexible training options for early-career clinician scientists.”
The contribution of clinician scientists in the new Cambridge Cancer Research Hospital will be critical for the future of cancer research. The East of England specialist cancer hospital planned for the Cambridge Biomedical Campus is bringing together clinical expertise from leading Addenbrooke’s Hospital with world-leading scientists from the University of Cambridge and Cancer Research UK Cambridge Centre, under one roof.
This integrated approach will help fast-track cancer innovations and will mean patients across the region can directly benefit from the latest innovations in cancer science.
Becoming a clinician scientist usually involves doctors taking time out of their medical training to undertake a PhD, before returning to train in their chosen specialisation, but many clinicians don’t come back to research after qualifying as consultants. This may be due to existing pressure on the healthcare system and lack of available funding.
Nearly three quarters (74%) of clinical research staff surveyed by Cancer Research UK in 2023 said that it has become harder to deliver research in a timely manner in the last 18 months, with 78% of respondents describing wider pressures on the health service as a substantial or extreme barrier.
To tackle this issue, Cancer Research UK’s Clinical Academic Training Programme provides flexible training options alongside mentorship and networking opportunities to better support clinicians who want to get involved and stay in cancer research.
Data from the Medical Schools Council Clinical Academic Survey reports a decline in the number of clinical academic positions between 2011–2020. Research from the United States also suggests that offering combined qualifications retains more women in clinical research roles.
Professor Richard Gilbertson, Head of the Department of Oncology at the University of Cambridge and Director of the Cancer Research UK Cambridge Centre, said: “We are delighted to gain further generous support from Cancer Research UK to enable us to provide doctors and medical students with flexible training opportunities, training them to be the clinical cancer research leaders of the future.
“Developing new and effective treatments of cancer requires teams of scientists working in the clinic and laboratory, in all specialities. This funding is crucial to ensure that we train these individuals so that we can make these discoveries to benefit patients with cancer well into the future.”
Adapted from a press release from Cancer Research UK
Cancer Research UK has announced £9.2m for Cambridge to train the next generation of doctors and scientists to bring new and better cancer treatments to patients faster.
I’m immensely grateful for the funding I received from Cancer Research UK, which provided me with a key stepping stone in my clinician scientist careerCaroline WatsonCambridge UniversityAddenbrookes Cancer Research Centre
The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.