Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Monkeypox (MPX) is a viral infection caused by monkeypox virus, previously largely confined to West and Central Africa, with occasional infections arising from international travel. Most cases before 2022 are likely due to people encountering animals who are infected with the virus, likely a rodent but possible many animals that live in West and Central Africa. However, since May 2022 there has been a large outbreak all over the world, largely affected gay, bisexual and other men who have sex with men (GBMSM). By the end of August 2022, over 3,200 cases had been diagnosed in the UK. There has been sustained human-to-human transmission, showing that infection is spreading from person to person rather than needing people to encounter an infected animal. Monkeypox is predominantly spread from close contact, likely from exposure to skin lesions (spots) or recently contaminated bedsheets of an infected person. The previous monkeypox infection looks a lot like smallpox, or chickenpox, with lesions (or raised spots which can turn into blisters filled with fluid) all over the body. In this new 2022 outbreak, people have been diagnosed with far fewer spots, presenting to sexual health services with limited spots in the groin region, or small ulcers that may go undiagnosed. It is not known how often people may be infectious before the onset of any symptoms and development of spots, or indeed inf people can be infectious without ever knowing they have monkeypox infection (asymptomatic infection). This is vital to our understanding of how well different control measures will work. If people are not infectious without obvious spots or symptoms, they will be able to be told what symptoms to look out for that means they should seek medical attention, particularly if they have been in close contact with someone who has had monkeypox infection (a case). If many people can be infectious without knowing it, this will severely limit the impact of messaging to be aware of symptoms to control any outbreak. Control will only be possible by achieving population level vaccination coverage with a highly effective vaccine, or by considerable change in behaviour. There is some previous evidence from smallpox, a related virus, and from prior antibody studies in West Africa that have shown likely asymptomatic infection (or infection with unrecognised minor symptoms) disease in people who live in areas where monkeypox is known to exist. Monkeys are also known to be able to be infected without symptoms. From the current outbreak, early research in sexual health clinics in France and Belgium has shown that several people can likely be infected without ever displaying symptoms or have detectable infection before symptoms develop. There are also preliminary indications from a small number of cases that transmission may be occurring early in infection, which may include before individuals have identified that they are symptomatic. However there is no study to date that looks at a group of contacts of monkeypox cases to determine in detail a) how common this is b) how long people may be infectious for. We will attempt to answer these questions by asking close sexual contacts of monkeypox cases who have either been identified from public health contact tracing or from self-referral from online social media recruitment to take swabs and urine samples, along with blood tests to look for antibodies, and answer an online questionnaire about symptoms and monkeypox exposure. We will also be able to compile these data to also get an estimate of how many contacts go on to develop monkeypox infection and for those who have been vaccinated, how effective the vaccine is. The study will be conducted through collaboration between laboratory teams at UKHSA, field epidemiology, immunisation, data processing, and statistical experts, relevant teams engaged in national incident response, sexual health peer experts, and academics in sexual health research.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

The discovery of deciphering the human genetic code has been a landmark scientific achievement, leading to the development of personalized medicine, gene therapies, or modern vaccines. Today, the genetic codes of major organisms, and viral or bacterial pathogens that compromise human health are identified (or sequenced) at low cost and at industrial scale, including for the purpose of reconstructing how infectious diseases spread in human populations, and how to stop spread. The genetic relationships of pathogen variants provide objective data about who infected who, information that is otherwise hard to obtain. The mathematical and statistical theory that underlies the analysis of these data is called 'phylodynamics'. This theory has made possible to reconstruct and quantify how anti-microbial resistant pathogens have spread worldwide, in communities, or in hospital wards, or how novel COVID-19 variants emerge and replace each other. This EPSRC project aims to develop a novel class of statistical phylodynamic theory, grounded in deep Poisson point processes, that are substantially more flexible and computationally faster than existing methods. Our preliminary findings indicate this approach has the potential to unlock the analysis of important questions about the age, behavioural characteristics, locations, mobility patterns or other characteristics of population groups that are the sources of pathogenic spread, and which to date are very challenging or impossible to address. We will develop the statistical theory and provide open-access and computationally scalable code for flexible and reproducible analyses. This project will benefit from close ties to the Machine Learning & Global Health network (development of deep non-parametric methods), the international PANGEA-HIV consortium (access to large-scale, rich and globally important data collected over the past 10 years), the UK Health Security Agency (aiming to use our methods in the UK) and to Oxford Nanopore (transitional industry impact).

ConnectomX proposes to join an existing relationship between the UK Health Security Agency (UKHSA) and the Central Laser Facility (CLF) to collaboratively develop a novel correlative light and electron microscopy (CLEM) workflow. This workflow will be applied to a UKHSA project imaging brain tissue for the presence of environmental pollutant particles. Together, the workflow will be tested, and proof of concept data will be collected to prove the utility of the Katana ultramicrotome as a universal solution to volume CLEM of tissue samples. The ConnectomX Katana ultramicrotome will be installed onto an existing scanning electron microscope (SEM) at the CLF. This will allow versatile switching between serial block face scanning electron microscopy (SBF-SEM) and focused ion beam scanning electron microscopy (FIB-SEM). ConnectomX will produce software and hardware solutions as part of an ongoing and iterative research and development collaboration to improve and build on the CLEM workflow pioneered in this proposal. More specifically, the proposed workflow is to image entire brain tissue sections using multiphoton microscopy (MPM) at low resolution to identify smaller regions of interest (ROIs) impacted by nanoparticle infiltration. These ROIs will be identified related to blood brain barrier (BBB) permeability and will later be relocated in the SEM for high-resolution imaging. The ConnectomX Katana ultramicrotome can be mounted within the chamber of the SEM at the CLF to perform serial SBF-SEM on selected brain tissue sections containing ROIs identified in MPM. SBF-SEM utilises a diamond knife to cut away a thin layer of the sample, after which the surface is imaged. This process is repeated thousands of times to build up 3D visualisations of the structure of a sample. In this proposal, the Katana ultramicrotome will be used to acquire a low-resolution volume dataset within each brain tissue sample. Blood vessels or branding marks (made using MPM) in these low-resolution datasets will be used to relocate smaller ROIs with BBB permeability. Incorporation of the Katana into the CLEM workflow would ensure the imaging is performed in a more efficient and robust way by significantly reducing experiment time and increasing sample throughput. In addition, SBF-SEM data collected during the proposed study will be used to facilitate development of an automated ROI recognition software, which can be used to stop cutting once the ROI has been located. This can significantly reduce operator time at the SEM as well as reduce unnecessary data collection. For each sample, once the final ROI has been located using SBF-SEM, the Katana ultramicrotome will be unmounted from the SEM and FIB-SEM will be used to explore the nanoparticles on a subcellular level. Data collected from this project will contribute towards the development of modified hardware and workflows that allow for FIB-SEM data to be acquired with the Katana still on the sample stage in the microscope. In-situ SBF-SEM and FIB-SEM will lead the way to automating CLEM from the electron microscopy point of view. This will truly push forward the boundaries of bioimaging at the nanoscale which is vital to fully understand how organelles, cells, and tissues function.