Current Projects
2018 – ongoing
Grant awarded: £1,351,673
Timescale: 4 years
Creation of a research microbiome laboratory facility.
As gut microbiome research is still in its infancy, there is a lack of consent for method standardisation across laboratories. The state of our facilities at the Department of Twin Research only allows us to store raw material collected from the twin’s visits. The department then relies on collaborators or companies to perform DNA extraction and sequencing. DNA extraction is a crucial step that can induce bias in the data if not performed under rigorous and uniform conditions. The large set of faecal samples collected over the years and the sparse nature of the twin’s visits has made it difficult to standardise DNA extraction. Consequently, the bias in the data has accumulated over the years. Also, the length of raw material storage can affect the outcomes of bacterial DNA sequencing. Performing DNA extraction in-house will allow controlling for these factors. The budget includes an amount for sequencing to be outsourced as the costs are a third of that offered by our hospital sequencing department, as it would struggle to handle the workload within two years.
2019 - ongoing
Grant awarded: £321,086
Timescale: 4 years
Targeting the gut microbiome and its metabolites to improve cardiovascular outcomes
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This study aims to identify specific factors that result in improved cardiovascular outcomes. The project will combine state-of-the-art high-throughput omics data from three population-based cohorts. The study will use extensive longitudinal CVD phenotyping and dietary data, to identify bacterial species, microbial metabolites, nutritional intakes and pathways that impact the host cardiovascular phenotypes. The goal is to advance our understanding of the mechanisms behind cardiovascular outcomes, with the potential to lead to effective prevention, intervention, and management strategies for treating cardiovascular diseases by targeting the gut microbiome and thus mitigating its health burden.
2019 – ongoing
Grant awarded: £704,689
Time scale: 3 years
Using the faecal metabolomics and serum glycomics to unravel the microbiome inflammatory pathways causative of cardiovascular disease.
This project will use data from over 4000 twins to find how the chemical substances produced by microbes in our guts positively or negatively influence heart disease. Using a method called “Mendelian Randomization”, we will investigate how a person’s genes influence the effect of the substances produced by microbes to determine which of these microbial substances are causing heart disease (as opposed to being an effect of people who are less healthy producing these substances). We will then generate a database of all these genetic/chemical substance/disease relationships and combine it with data from a recent nutrition study called PREDICT. In the PREDICT study, we gave 1000 people a very high fat content meal to raise fat and cholesterol in blood and to increase levels of proteins with sugars attached to them. These are called “glycosylated” proteins. We will see how the type of substances produced by microbes affect the increased levels of cholesterol in blood and of these glycosylated proteins. This will help us understand how to individually modulate a person’s diet to reduce heart disease risk.
2020 – ongoing
Grant awarded: £522,983
Time scale: 24 months
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The Covid Symptom Study: The Genetics of Long COVID-19
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COVID-19 can be severe and sometimes fatal, but most individuals experience symptoms for 1-2 weeks. However, 12% of infected individuals report symptoms, particularly fatigue and headache, lasting longer than four weeks and 2.5% longer than eight weeks, often for many months. Complicating matters, some individuals with long-term symptoms have a negative COVID-19 test. Why some individuals have long-term symptoms is unclear, but inflammation (how the immune system helps clear infection) appears to be the likely explanation. If so, this will be important when developing a safe vaccine.
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Because of their genes, some people are more likely to get infections, including Covid-19. The recent twins' study found that genes explain almost half the risk of catching COVID-19. Genetic studies on COVID-19 have been small and focused on severe infection. No one has studied long COVID-19 genetics or compared long COVID-19 with the short or asymptomatic disease. Genetics also determine immune system responses, like inflammation and many auto-immune diseases. Knowing the genes responsible for these conditions will help investigate the genes involved in COVID-19. Finally, genes also shape the microbiome. The interaction between our genes and the microbiome may also contribute to COVID-19.
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2023 - ongoing
Timescale: 5-year longitudinal study
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TwinsUK Imaging: A Resource for Ageing Research.
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The five-year longitudinal study will use members of the TwinsUK cohort to investigate the ageing process. TwinsUK is the UK’s largest adult twin registry and the most clinically detailed worldwide. Using whole-body MRI scans, the project will enable researchers to investigate the influence of environmental factors on ageing and the development of age-related diseases. The research will focus on normal brain ageing, the genetic and environmental determinants of cognitive decline, age-related cardiovascular change, and how diet affects ageing.
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Whole-body Magnetic Resonance Imaging (MRI) enables the non-invasive characterisation of the structure and function of multiple organs simultaneously, providing objective measurements of pathological and ageing processes. In young adulthood, twins are highly similar in most organ structures, but with age, this within-pair concordance weakens as they are progressively exposed to different environments (1). Thus, twin studies are an ideal design to investigate the influence of environmental factors on ageing and the development of age-related diseases, such as neurodegenerative disease, heart failure, liver steatosis and cancer. TwinsUK is a large adult UK twins study with over 25 years of longitudinal multi-omic biological data, clinical measures and comprehensive record linkage (2). TwinsUK Imaging will provide state-of-the-art multi-organ phenotyping, which, linked with the longitudinal datasets, will be used to understand how factors such as COVID-19 infection and lifestyle influence organ-specific ageing and disease.
This project aims to create a comprehensive imaging resource within the TwinsUK cohort to further our research programme on ageing-related disease and early cancer detection. Specific objectives include: (i) the creation of organ-specific ageing biomarkers from imaging data using UKBiobank and applying these in TwinsUK to identify twin-pair ageing differences, (ii) the use of machine learning and hypothesis-driven approaches to identify exposures differentiating twin-pairs about specific organ ageing, (iii) identify longitudinal imaging correlates of COVID-19 exposure, using discordant twins for COVID-19.
2022 - ongoing
Timescale: 24 months
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Enhancing the TwinsUK biobank with a new Laboratory Information Management System (LIMS)
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TwinsUK is a large-scale health and ageing population study with extensive genetic and health data from over 15,500 adult twins from multiple time points over 30 years of research. TwinsUK began recruiting twins in 1992 and collecting long-term biological samples, which are stored in our biobank. The biobank holds approximately 700,000 samples in freezers, cryogenic tanks, and other storage facilities. The current biobank databases were designed in 1996. These databases have become large and complicated to maintain.
The LIMS will modernise the laboratory processes and storage facility in the next two years. TwinsUK Biobank is committed to sustainability. The LIMS upgrade will help reduce freezer numbers to reduce overall energy consumption and carbon footprint.
2023 - ongoing
Timsescale: 36 months
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Impact of diet and plant diversity on presumed markers of cardiometabolic health
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Cardiometabolic diseases are an increasing burden on global health, with cardiovascular disease representing the leading cause of death worldwide. A Western Diet, characterised by consuming refined grains and processed foods, is associated with increased cardiometabolic disease risk. These foods are known to negatively impact a host’s gut microbiome which holds a mediating role in cardiometabolic disease. Microbiome species diversity is an indicator of good cardiometabolic health. The project will generate new insight into dietary microbiome features through the lens of dietary diversity with the aim of contributing towards new intervention strategies for cardiometabolic diseases.
Using already collected data from large studies, and in particular PREDICT1, PREDICT3, and TwinsUK, this PhD project has the following four aims: (i) characterise diet diversity and its variability in the UK population, (ii) use these data to characterise a simplified short questionnaire that can be used to assess diet diversity, (iii) investigate the association between diet diversity and in particular, plant diversity and, markers of cardiometabolic health, and (iv) understand the involvement of the gut microbiome in mediating this association.
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2023 - ongoing
Timscale: 36 months
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The role of the microbiome in Low Back Pain
Chronic low back pain (LBP) is a global issue. It is now the leading cause of disability worldwide. Intervertebral disc (IVD) degeneration is an age-related trait and a significant risk factor for LBP. While degenerative conditions are not generally considered inflammatory and are not caused by infection, recent evidence suggests that disc degeneration (DD) may be caused by a very low-grade infection in some people. Recent advances in microbiome techniques allow us to explore small fragments of bacterial DNA that provide evidence of the presence and potential infection. In addition, chronic pain is linked to a raised body mass index (BMI), which is related to an altered microbiome in the gut.
This project will explore the various mechanisms by which the microbiome might influence LBP. First, by investigating the relationship between LBP and BMI in a cohort of TwinsUK who have spine imaging and gut microbiome sampling. Second, by examining IVD samples collected from hospital patients undergoing spine operation. The hypothesis is the alteration in the microbiome is responsible for LBP. This will be the first study to determine specifically if microbial DNA is present in the disc and to identify the source of that material by searching other anatomical sites for similar microbes
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2024 - ongoing
Timescale: 48 months
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The relationship between diet, gut microbiome, exercise and sarcopenic obesity.
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Sarcopenic obesity (SO) is a geriatric syndrome characterised by a dual burden of sarcopenia (low muscle mass, reduced muscle strength and physical dysfunction) and obesity (excess fat), resulting in many adverse clinical complications and likely increasing in prevalence as populations around the world continue to age. Different factors, including ageing, diet and a sedentary lifestyle, contribute to SO’s development, although the pathogenesis remains unclear. Twin pairs provide valuable insights into the interplay between genetic and environmental factors in the development of SO and could point to novel ways of preventing or treating SO. This PhD project will use existing longitudinal TwinsUK data on more than 3,000 twins and novel data collection on 200 twins to explore modifiable risk factors linked with SO, including diet, the gut microbiome, and physical activity.
The PhD project will take a novel approach to (i) identify the factors associated with SO, utilising existing data with the extensively phenotyped TwinsUK cohort, (ii) investigate the impact of diet, exercise and gut microbiome composition on SO utilising both existing and newly collected data, (iii) study the effect of SO on an individuals’ quality of life, using a mixed quantitative and qualitative approach. The hypothesis is that differences in diet, gut microbiome and exercise are linked to the development of sarcopenic obesity.
