ROYAL VETERINARY COLLEGE
universityTotal disclosed
$9,691,086
Award count
10
Distinct programs
1
First → last award
2024 → 2030
Disclosed awards
Showing 1–10 of 10. Public data only — SR&ED tax credits are confidential and not shown.
UKRI Gateway to Research · FY 2026 · 2026-06
Over 40% of farmed fish and shellfish die due to infectious diseases in some aquaculture systems, most because of viruses. Virus outbreaks in aquaculture therefore harm welfare, cost £5 billion annually, and hinder production sustainability. A 35% expansion of aquaculture is planned by 2030 to feed a growing global population. Increased market connectivity, larger and denser aquatic populations, and sectoral growth in countries with poor biosecurity will likely worsen outbreaks. We urgently need new strategies to prevent this. In the widespread absence of vaccines and prophylaxis, strategies to reduce virus spread rely on interventions like movement bans, equipment cleaning, or culling. To deploy these better, we need to know (i) how viruses move between facilities and (ii) the effectiveness of control measures. The former is not captured by infection data. The latter cannot be easily quantified through measuring observed disease, in part because other fish health metrics (e.g., stress) may affect disease severity and likelihood of observation. My Fellowship will address this challenge using advances in virus genomics, and computational tools that enable genomes to be analysed along with other big data types. I will achieve this through focus on farmed Atlantic salmon (Salmo salar), the most important aquatic species in the UK. O1: Resolve the importance of boat-mediated virus transfer of non-notifiable viruses. Salmon farmed at sea are serviced by boats and kept in nets through which seawater flows. Both virus flow in water or on contaminated equipment could cause infections, but resolving the relative importance of these is tricky because patterns of higher virus movement between neighbouring farms is explainable by both. I will solve this through bait-enriched genomic sequencing and phylodynamic analysis of endemic viruses in marine sites that present repeated “natural experiments” across Norway, allowing discrimination between the importance of these transmission modes for diverse common viruses including piscine myocarditis virus. O2: Develop approaches to measure the importance of virus dispersal modes by joint analysis of multiple data types. Natural experiments are insufficient for pathogens not circulating within them. We need new tools that can analyse virus genomes together with complex dynamic network information on water current data and boat/fish movements to enhance tracking and prediction of spread. I will develop new computational approaches that allow us to better integrate movement networks, disease case data and virus genomes. O3: Enable producer-personalised solutions to controlling endemic disease. Producers are frustrated by the lack of evidence to guide their actions to try and control non-notifiable endemic diseases. Massive, detailed data on fish health and their environment, already monitored confidentially across sites, could be used with virus genomes to seek innovative and personalised control measures. Working with a multinational producer, I will conduct a high-resolution, longitudinal virus genomic epidemiological study on two sites, bringing together data types to improve producer-led interventions. Success in my objectives will contribute to reducing salmon disease. Collaborating with industry leaders and government will ensure effective translation across scales. Aquaculture – and animal health more broadly - is in the early stages of a major shift towards routine virus genome sequencing. My work will therefore be important in establishing and proving methods to maximize the value of growing genomic datasets at an early stage of need. Reducing virus outbreaks will improve aquatic animal welfare, enable sustainable industry growth, protect wild populations, and reduce consumer costs.
UKRI Gateway to Research · FY 2026 · 2026-03
Middle East respiratory syndrome coronavirus (MERS-CoV) is one of three deadly zoonotic betacoronaviruses to emerge globally in the past two decades. The first known MERS outbreak occurred in a hospital in Jordan in 2012. Since then, as of May 2025, a total of 2,638 cases and 957 deaths have been reported, most of them in the Arabian Peninsula. With a high case fatality rate and ongoing zoonotic transmission, MERS-CoV remains a significant public health threat and is classified by the World Health Organisation (WHO) as a priority pathogen, given its potential for large-scale outbreaks and pandemic risk. In Jordan, MERS-CoV is a recognized One Health priority by both the Ministry of Health (MoH) and the Ministry of Agriculture (MoA). This project addresses a key evidence gap by evaluating two interventions: behavioural changes and camel vaccination to reduce zoonotic MERS-CoV transmission within high-risk camel-owning households in Jordan. The study uses a randomized factorial design to evaluate the protective effects of a behavioural intervention package and camel vaccination, both separately and in combination. The behavioural intervention, which has been recently piloted successfully, promotes safer camel-handling practices, improved hygiene, and management of comorbidities, while the camel vaccination employs the MVA-MERS-S vaccine, which has been shown to reduce viral shedding in camels and to protect against camel pox. A registry of camel-owning households maintained by Jordan’s MoA will be used to recruit 700 households to randomise into the four trial arms including a control arm. Outcome measurement will include RT-qPCR testing of nasal swabs in household members, observational assessments of behaviour as well as process measures. The primary outcome will be the reduction in positive MERS-CoV RT-qPCR of nasal swabs. In addition, the trial will assess viral shedding and serological responses in camels as secondary outcomes, providing further evidence of vaccine impact and field performance. The project builds on a decade-long partnership between institutions in the UK, Jordan, and the US, combining expertise in epidemiology, virology, anthropology and community-based interventions. Our team was the first to identify MERS-CoV in dromedary camels in Jordan, providing evidence of its zoonotic transmission and identifying risk factors in both camels and humans. More recently, in a pilot trial evaluating behavioural changes to mitigate MERS-CoV exposure, our team conducted systematic community-based RT-qPCR testing of respiratory samples from members of high-risk camel-owning households, detecting multiple asymptomatic infections prior to any intervention. Despite their considerable potential, robust trials of interventions in animals to protect humans are rare. In line with One Health principles and the WHO's emphasis on integrated strategies to tackle health risks at the human-animal interface, this project represents such an approach. The anticipated outcomes are to provide actionable evidence to support the sustainable deployment of interventions in Jordan and other high-risk settings. The project prioritizes responsible research practices, including community engagement, co-leadership with Jordanian researchers, and local capacity building, ensuring interventions are culturally appropriate and sustainable. We partner with the World Organization for Animal Health (WOAH) and the Food and Agriculture Organization of the United Nations (FAO) underscoring the project’s alignment with both regional and international priorities and enhancing its potential for scalability and broader implementation. This research will not only provide critical evidence to mitigate MERS-CoV transmission and strengthen global health security but also serve as a model for addressing zoonotic diseases through integrated human-animal health approaches.
- On-demand cell-autonomous gene therapy as a novel treatment for dogs with pharmacoresistant epilepsy$909,406
UKRI Gateway to Research · FY 2026 · 2026-02
Epilepsy, the most common neurological disorder in pet dogs, has profound detrimental effects on both quality of life and lifespan. Treatment consists of long-term administration of antiseizure medications but around one third of affected dogs fail to respond and severe side effects of the medications are commonly encountered. As a result, many pet dogs are euthanised when their epilepsy becomes unmanageable. Novel treatment approaches are urgently needed in veterinary practice, as they are in human medicine, where epilepsy has a very similar prevalence. We have developed an entirely novel approach for treating seizures that utilises a viral vector to carry a gene therapy into the brain. The therapy specifically targets the overactive cells responsible for the initiation and propagation of seizures. It then reduces the activity of these overactive neurons but only for as long as they exhibit abnormal activity, so resulting in a persistent antiseizure effect without interfering with the function of normal surrounding neurons. If the seizures stop, the genetic therapy switches itself off, unless and until excessive activity recurs. We have previously demonstrated safety and efficacy of this antiseizure gene therapy in mice, with further efficacy data from human cells grown in culture. Furthermore, we have shown that the therapy does not interfere with physiological behaviours in mice. In this project we will work to optimise the gene therapy for use in dogs by testing different versions of the construct in dog cells grown in culture. We will then undertake a clinical trial in dogs with severe epilepsy, where the seizures are non-responsive to medication and in whom the quality of life is significantly compromised. Under general anaesthesia, the dogs will receive a single injection of the optimised construct and will then be monitored for at least 6 months. During this time, we will assess their seizure frequency and duration, their general brain health and behaviour, and we will monitor for any adverse effects of the treatment. The gene therapy will be injected into the cerebrospinal fluid (the fluid that bathes the brain) as this is a well-tolerated and non-invasive means of achieving widespread and focused access to the brain. A significant advantage of our therapeutic strategy is that it does not require identification of the location of the seizure-initiating neurons (which is generally not possible in dogs). The gene therapy will only be switched on in neurons that exhibit pathological activity. Thus, the epileptic foci are identified by the therapy and not a priori. In summary, we aim to test a first-of-its kind gene therapy for canine epilepsy with potential for long term seizure control following a single injection. This could be transformative to the lives of affected dogs, as well as their owners, and offers significant translation potential for other veterinary species and for people with a range of seizure disorders.
UKRI Gateway to Research · FY 2025 · 2025-11
Antimicrobial resistant bacteria, and especially the problematic multi-drug resistant (MDR) bacteria, are a threat to all healthcare, limiting our ability to prevent and treat infection. MDR bacteria acquire and maintain multiple resistances, even without selective pressure in their natural habitat, which is usually the colonised human host. While much is known about gene transfer mechanisms, relatively little is known about how AMR gene transfer is controlled, regulated and stably maintained in MDR bacterial pathogens. The aim of this project is to investigate newly discovered genes in the MDR pathogen methicillin-resistant Staphylococcus aureus (MRSA) that control the horizontal gene transfer (HGT) and stability of AMR. MRSA is the most common cause of AMR death globally. In the last 20 years, increasingly MDR-MRSA clonal types have emerged on multiple occasions causing new clinical problems (e.g. Healthcare MRSA, Community MRSA, Livestock MRSA), while we wait for expected further resistance and epidemiological combinations to establish and spread (e.g. Vancomycin Resistant MRSA, Livestock MRSA in humans), potentially affecting all aspects of healthcare and medicine. In these populations, resistance genes to nearly all classes of antimicrobials are carried on relatively unstable and individual mobile genetic elements. These AMR genes are also highly mobile, as human and animal carriage studies indicate they are exchanged between populations at high frequency during colonisation, with only a few individual cells displaying full MDR phenotypes. MRSA benefits from HGT to acquire useful DNA that protects population survival upon new environmental exposures, such as antimicrobial exposure. However, MRSA also needs barrier systems to protect from foreign DNA (such as lytic bacteriophage) that can be harmful. Known barrier mechanism examples include restriction-modification systems and CRISPR. However, successful MDR-MRSA clones have additional uncharacterised barrier mechanisms which likely play a key role in their survival and successful spread. These barriers of HGT also make MRSA particularly difficult to manipulate genetically in the laboratory. Using a transposon library screen and a novel co-culture gene transfer assay (CoGTRA) to assess AMR gene transfer and stability, we have identified several new barrier gene pathways that control successful HGT and located many of them to a new putative mobile genetic element, the S. aureus Transfer Island (SauTI). In addition, several SauTI genes are predicted to respond to environmental triggers. In this project we will Define the SauTI element and its distribution and evolution in successful MRSA populations. Characterise newly identified genes that control SauTI mobility, AMR HGT and stability Identify how AMR HGT is reduced or enhanced by environmental conditions. Our results will Identify how to optimise gene transfer assays to build better tools for the genetic manipulation of aureus and potentially other cells (biotechnology). Identify targets and strategies to manipulate AMR gene acquisition and stability in models of MDR-MRSA evolution relevant to the colonisation habitat Identify markers for diagnostics or epidemiological studies to identify patterns of evolutionary adaptation and risk of the emergence of new MDR-MRSA clones. Together the results from these studies will advance our understanding of how MDR pathogens acquire and stably maintain AMR genes in the absence of selection, generating insights into evolution, epidemiology and how this might be manipulated in the laboratory, in patients or the environment to reduce the incidence of MDR-MRSA infection.
UKRI Gateway to Research · FY 2025 · 2025-09
The development of agile, adaptable and robust engineered systems continues to be accelerated by insights from nature. To control fast movement, animals must rapidly and effectively estimate the instantaneous state of motion and loading of their body-parts using sensors. The same is true for engineered systems such as autonomous vehicles and wearable technology, yet they typically use much more computationally-intensive neural networks. Artificial neural networks are famously bio-inspired and have revolutionised data processing but they continue to operate on von Neumann-style processors, take inputs from traditional sensors, and often fail in unfamiliar situations outside those experienced during training. This is at odds with evolved locomotor control strategies in animals, which have fundamentally different approaches and exhibit superior performance across a range of tasks, including dealing with novel, sparse, noisy and incomplete data. One theory for why animal sensorimotor performance excels, is the co-evolution of mechanosensory apparatus with the architecture it observes. This enables passive, physical filtering of the potential broadband information, passing through only salient features to be encoded by the peripheral nervous system: this is the essence of morphological computing. A key challenge for biologists and engineers alike is to understand how sensorimotor control is achieved, leading us to hunt for tractable animal models that can be interrogated comprehensively. The true flies (Diptera, including the genetic model species Drosophila melanogaster) have been particularly useful in this respect, with an ever more complete knowledge of how the compound eyes and the halteres (vestigial hindwings instrumented with strain sensors that detect body rotations via inertial forces) operate, with mechanosensation having a speed advantage over visual processing. The wings are richly sensorised in a homologous manner to the halteres and experience a complex combination of inertial and aerodynamic forces. However, they are less studied, leaving an incomplete understanding of sensorimotor flight control. Our aim here is to create a general model of wing mechanosensing that reveals the principles of co-evolved sensor distribution and morphology. We will measure multi-scale body and deforming wing kinematics of eight fly species with diverse wing shapes, wingbeat frequencies, and flight behaviours. We will test hypotheses of species-specific sensor placement patterns, to determine whether locations are matched to the aeroelastic strains experienced by each species across their typical flight parameter space. This will reveal whether the architecture is filtering sensory cues prior to encoding—such that perception is tuned to useful information only—thus reducing the computational burden and demonstrating morphological computing (also known as embodied intelligence). We will integrate our findings with published electrophysiological responses of strain sensors to test whether sensitivity to physical cues matches the signals they experience. Finally, we will incorporate a scaling analysis of wing architecture and wingbeat frequency to maximise the applicability of the general principles we discover to embodied control systems more widely. The large dataset of deforming wing kinematics, from multiple fly species, will be unprecedented in scope and detail, forming a valuable open source dataset. Our results will be of significant interest to biologists and engineers, with application to sensory physiology, arthropod evolution, functional morphology, neuromorphic computing, sparse sensing, and adaptive control for autonomous vehicles and robotics. This is curiosity-driven, data-intensive, frontier bioscience addressing fundamental questions in biology. It sits within the BBSRC priority area Frontier bioscience: understanding the rules of life, with clear application to Transformative technology.
UKRI Gateway to Research · FY 2025 · 2025-06
Malaria is a significant and continuing health problem facing half of the world’s population resulting in ~600,000 mortalities annually, predominantly children. The causative agents are Plasmodium parasites, which are transmitted by mosquitoes and replicate in red blood cells (RBCs) of their host. Like other vector-borne diseases, malaria is predicted to increase its spread with the effects of climate change, making a meaningful intervention critical. Of the six human-infecting species Plasmodium falciparum (Pf) is the best studied; it is widespread, especially in Africa and most virulent. Groundbreakingly, two malaria vaccines targeting Pf have recently been approved. However, no vaccines are available against the prevalent Plasmodium vivax (Pv) which dominates outside of Africa or the South-East Asian parasite Plasmodium knowlesi (Pk). Neglected human malaria parasites Pk and Pv have proven difficult to control which hinders ongoing malaria eradication efforts. We are molecular parasitologists/vaccinologists targeting blood stages of Pf, Pv, Pk and have developed controlled human malaria infection trials (CHMI) allowing us to quickly progress vaccine candidates from the bench to clinical testing. As Pv cannot be maintained in vitro we established a transgenic parasite model using the closely related Pk to express orthologous Pv genes. Using CRISPR-Cas9 we can modify Pk genes to generate knockouts, whole gene or domain swops. Our combined expertise allows us to test antigens both as targets for neutralising antibodies and to explore their functional conservation for RBC invasion across Plasmodium species boundaries with the aim to translate these discoveries into cross-protective vaccines. A pentameric protein complex, comprised of PTRAMP, CSS, RIPR, CyRPA and RH5 called PCRCR is critical for invasion of RBCs by Pf and we recently identified part of this complex’s structure. The complex binds to basigin on the RBC via RH5. This interaction is essential for invasion. RH5 is the leading Pf blood-stage vaccine candidate with neutralising antibodies blocking RH5 from recognising basigin and recently showing efficacy against clinical malaria in young African children for the first time. However, RH5 is exclusive to Pf, whereas the other protein complex components show conservation in Pv and Pk. Preclinical testing of PfRIPR identified growth inhibitory epitopes within the RIPR tail, since validated by human vaccination in a Phase 1 clinical trial. We further discovered that PkRIPR is part of a protein complex with PkCSS and PkPTRAMP and essential for RBC invasion. Antibodies targeting PkRIPR also blocked RBC entry. This emphasises RIPR’s functional conservation for RBC entry across all Plasmodium species studied to date. Our proposal addresses the following complementary aims: 1.Validate and functionally explore additional protein interactors of the PkPCR+ complex and their conservation between Pk and Pv. 2.Characterise species-specific and cross-protective neutralising epitopes in PkRIPR and PvRIPR. 3.Define mechanisms how neutralising RIPR-specific mAbs block RBC entry by merozoites. This project will use reverse genetics, cell biology, protein biochemistry, proteomics and vaccinology approaches using Pk as a model for Pv. The study outcome will result in discoveries detailing the composition and essential function of the PCR+ complex for RBC invasion across Plasmodium species, which will significantly advance the generation of a Pv/Pk cross-protective malaria vaccine.
UKRI Gateway to Research · FY 2025 · 2025-04
With growing demand for protein from animal origin, the poultry industry is experiencing an unprecedented intensification in Southeast Asia. Industrialisation of livestock farming is accompanied by an overuse/misuse of antimicrobial drugs (AMD) which is believed to be a significant driver of antimicrobial resistance (AMR). AMR is a major threat for human and is reported to be responsible for close to a million deaths, yearly. The team assembled in this project has worked together within the UKRI GCRF One Health Poultry Hub, to generate robust evidence of excess AMD use in poultry production systems within Vietnam, using a holistic One Health approach that integrates studies from biological and social science disciplines. This foundation has generated knowledge on the overall structure and vulnerability of poultry production systems in Vietnam, with insights into the lives of farmers and other actors, including differences in the roles, responsibilities and behaviours of men and women working across the network. It also highlighted an alarming prevalence of food-borne pathogens in chickens, showed that chicken gut bacteria and microbial communities have high levels of AMR genes resulting in resistance to many AMDs, and that AMD residues over the maximum residue limit (MRL) are present in ~ 9% of meat on sale to the public. This project will continue the interdisciplinary approach to generate new knowledge on the dynamics of AMR acquisition during the production cycle, to understand the drivers of high AMD use in Vietnam chicken production, and to investigate potential impacts of unintentional exposure to AMD and resistant bacteria by ingestion of contaminated water (chickens) of food (chickens and humans). The objectives of the OHRIGAME project (One Health Rationale to Investigate the emerGence of AMR related to chicken Meat and Egg consumption) are to: Through longitudinal sampling, evaluate AMR in chicken gut bacterial populations during their breeding until sale Use forensic investigative analyses to identify underlying reasons for the high level of veterinary drugs in meat, by analysis eggs, chicken feed and drinking water, and relate this to AMR profiles within the same chickens. The Vietnamese government’s ban of prophylactic antimicrobial use, coming into place in 2025, will constitute a natural intervention. Use questionnaire based research to understand farmers’ motivations for under-reporting use of AMD. We will also sample chicken meat imported from Vietnam and hospital-grade food in the UK to evaluate the risk of that AMD residues and AMR genes could pose to clinical populations of patients at risk of gut bacteria dysregulation. From the start in Vietnam we will work with local and national stakeholders from government, particularly the Department of Animal Health within the Ministry of Agriculture and Rural Development, with whom we have a well-established relationship, and with the One Health Partnership secretariat, agencies, NGOs and the poultry sector. With expansion of analysis capacity, we will propose a framework to increase Vietnam capability to screen AMD residue and AMR in chicken meat production to protect the national consumers, a key priority of the Vietnam’s Decision No. 4 14 /QD-TTg (Strengthening capacity to manage and control animal diseases and diseases transmitted between animals and humans).Our international One Health approach includes AMR diplomacy actions which will benefit people locally in Vietnam and is completely aligned with the UK National Action Plan on AMR.
UKRI Gateway to Research · FY 2024 · 2024-11
X-ray microcomputed tomography (microCT) is a non-destructive, precise procedure that allows the 3D imaging of biological samples at high resolution. This application is requesting funds to purchase a state-of-the-art, next generation microCT scanner, specifically a Neoscan N80 desktop microCT. The applications of this technology are broad but the primary use of the requested system would be for fundamental bioscience research across disciplines including musculoskeletal, cardiovascular, renal, developmental and neurobiology as well as biomechanics. Consequently, this system would be used to facilitate novel research that is directly relevant to the strategic aim of the BBSRC to advance frontiers of bioscience discovery. This application is requesting a Neoscan N80 scanner because it is the most advanced benchtop microCT available and has technical capabilities that far exceed other models. Specific advantages of the system include: (1) a spatial resolution of ~1micron, (2) x6 increased scanning capacity, (3) x4-6 faster scanning speed and automated sample loading, (4) temperature control, (5) in situ loading capabilities, (6) reduced noise, enhanced image correction and 3D reconstruction, (7) accessible and easy to use software and (8) improved environmental credentials (predicted lifespan >20 years). By combining all of these advantages, the N80 can rapidly produce higher quality 3D images of biological tissues with enough detail to allow the visualisation of small intricate structures much more readily. Furthermore, the greater scanning space and field of view will allow the analysis of samples previously too large to be imaged using a benchtop machine. This enhanced function and improved accessibility will also open the technology to many new users who, until now, have been unable to exploit the benefits of microCT scanning in their research. The applicant team are all part of the Royal Veterinary College (RVC) musculoskeletal research group. The research undertaken by the applicants is multidisciplinary and ranges in scale from transcriptomics and cell biology through to in vivo small and large animal studies. Musculoskeletal biology is an area of bioscience research where microCT is an established and essential tool. Indeed it is the only effective way to assess bone architecture and, consequently, skeletal integrity. Therefore, the applicants are all very experienced with this technology and the important information it can generate to transform approaches to skeletal analysis. MicroCT is also a well-used method in biomechanics research and an emerging technique in many others (e.g. cardiovascular, renal, developmental and neurobiology). The technical advantages of the N80 system mean that it will allow biological samples to be studied and analysed in new, more detailed ways. This will generate novel information about how structure influences function in many different tissues and make the N80 a crucial research tool for internal RVC researchers and external project partners working in a range of biological disciplines. Obtaining this next generation microCT system would represent a significant enhancement of imaging capability within London and the South East. The substantial demand for the machine will also help to establish, grow and sustain research collaborations between the RVC, other academic institutions and industry for many years.
UKRI Gateway to Research · FY 2024 · 2024-08
More than 280 tonnes of antimicrobial drugs (ionophores, commonly not classified as antibiotics) are used in UK poultry production every year, primarily to control parasites such as Eimeria. The global use of ionophores is unclear, but is likely to exceed 16,000 tonnes per annum. Public and legislative pressure is calling for reduced ionophore use, but the emergence of three new Eimeria species that can escape current vaccines and reduce economic performance risk prolonged use. Ionophores can also control bacteria such as Clostridium perfringens and the disease necrotic enteritis, but have been associated with selection for transferable elements that facilitate ionophore resistance in Enterococcus faecalis and Enterococcus faecium, and co-occurrence with genes that confer resistance to erythromycin, tetracycline and ampicillin. Enterococcus are bacteria that infect chickens but can also cause disease in humans - the spread of antimicrobial resistance genes (ARGs) could undermine animal as well as human health. Here, we aim to understand Eimeria population biology, including emergence of new types and the consequences of cross-fertilisation (hybridisation), interactions with the host, intestinal populations of bacteria and ionophore or vaccine selection. In parallel, we will use the same chickens and samples to define the consequences of ionophore use in commercial poultry populations on the occurrence of ARGs that could flow into food chains and the environment. Combined, this project offers a holistic approach to understand Eimeria population biology and the consequences of ionophore use as essential steps towards reducing reliance on ionophores in chicken production.
UKRI Gateway to Research · FY 2024 · 2024-08
Locomotion is among the most important function involved in tetrapod evolutionary success. Understanding how locomotion in current species evolved implies to study their fossil record. Evolutionary biomechanics tackles this topic, by estimating locomotor abilities of extinct organisms by observing their extant relatives. Particular efforts have been made to infer the locomotion in non- avian dinosaurs and other extinct archosaurs. However, as in most other tetrapods, archosaur limb bones have cartilaginous epiphyses that do not fossilise. This leads to high levels of uncertainty when conducting biomechanical analyses on such animals. Surprisingly, corrective strategies remained rather subjective and simplistic, failing to propose a robust way to account for missing cartilage. Here I propose to answer to this critical issue by concretely REconstructing the LOst CArTilaginous Epiphyses of extinct archosaurs, using cutting-edge quantitative methods. Focusing on the femur, the three-dimensional characteristics of a large sample of archosaurs will be used to estimate the missing epiphyses of fossil species. Subsequently to the study of modern morphological diversity, I will develop the protocol by assessing its accuracy to reconstruct epiphyses in a controlled virtual experimentation on extant species. I will also stress robustness to sampling variability to give the degree of confidence to put on the reconstruction. Finally, the impact of reconstructions will be tested by conducting a comparative biomechanical analysis. At the crossroads of quantitative vertebrate palaeontology, evolutionary biology and biomechanics, the project ambitions to develop the most objective and reliable way to date to reconstruct the lost epiphyses in extinct archosaurs. The unprecedented outcomes of the project should deeply impact inferences about how extinct archosaurs could locomote, and will open perspectives to generalise the approach to any other tetrapod group.