Current Projects
2019 - ongoing
Timescale: 4 years
Targeting the gut microbiome and its metabolites to improve cardiovascular outcomes
This study aims to identify factors influencing cardiovascular outcomes by analyzing high-throughput omics data from three cohorts. It will examine longitudinal phenotyping, dietary data, bacterial species, microbial metabolites, and nutritional pathways affecting cardiovascular health, with the goal of informing prevention and treatment strategies targeting the gut microbiome.
2020 – ongoing
Timescale: 24 months
The Covid Symptom Study: The Genetics of Long COVID-19
COVID-19 can be serious, but most people recover within 1–2 weeks. About 12% experience symptoms such as fatigue and headache for more than four weeks, and 2.5% for over eight weeks; some persist for months, even with negative tests. The cause of long-term symptoms is unclear but likely related to inflammation, which matters for vaccine development.
Genetics play a major role in infection risk—studies show they account for nearly half of the likelihood of contracting COVID-19. Research has mainly focused on severe cases, not on long COVID or asymptomatic cases. Genes influence immune response, inflammation, autoimmune diseases, and even the microbiome, all of which may affect COVID-19 outcomes.
2023 - ongoing
Timescale: 5-year longitudinal study
TwinsUK Imaging: A Resource for Ageing Research.
The five-year study will collaborate with TwinsUK, the UK's largest adult twin registry, to investigate ageing. Using whole-body MRI scans, researchers will study environmental effects on ageing and related diseases, focusing on brain ageing, cognitive decline, cardiovascular changes, and dietary impacts.
Whole-body MRI is a non-invasive technique that assesses the structure and function of multiple organs simultaneously, providing objective insights into disease and ageing. Twins often have similar organ structures in early adulthood, but these similarities decline over time due to differences in their environments. This makes twin studies valuable for analysing environmental impacts on ageing and diseases such as neurodegeneration, heart failure, liver steatosis, and cancer. With over 25 years of multi-omics data, clinical measurements, and record linkage, TwinsUK is a key resource. Its imaging project offers advanced multi-organ phenotyping to study the effects of COVID-19 and lifestyle on organ ageing and disease.
The project aims to create a detailed imaging database for the TwinsUK cohort to support ageing-related disease research and early cancer detection. Goals include: (i) developing organ-specific ageing biomarkers via UKBiobank data to compare twin pairs, (ii) using machine learning to identify exposures affecting organ ageing, and (iii) finding long-term imaging indicators of COVID-19 in discordant twins.
2022 - ongoing
Timescale: 24 months
Enhancing the TwinsUK biobank with a new Laboratory Information Management System (LIMS)
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 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
Timescale: 36 months
Impact of diet and plant diversity on presumed markers of cardiometabolic health
Cardiometabolic diseases, with cardiovascular disease as the leading cause of death globally, are a growing health concern. A Western diet rich in refined grains and processed foods increases risk by reducing gut microbiome diversity, a key indicator of cardiometabolic health. This project aims to explore dietary microbiome features in relation to dietary diversity to develop new intervention strategies.
Using data from extensive studies such as PREDICT1, PREDICT3, and TwinsUK, this PhD project aims to: (i) characterise diet diversity and its variability in the UK, (ii) develop a simplified short questionnaire to assess diet diversity, (iii) explore the link between diet diversity, especially plant diversity, and cardiometabolic markers, and (iv) examine the gut microbiome's role in mediating this relationship.
2023 - ongoing
Timescale: 36 months
The role of the microbiome in Low Back Pain
Chronic low back pain (LBP) is a leading global disability, often linked to intervertebral disc (IVD) degeneration, an age-related risk factor. While degenerative conditions are usually not considered infectious, recent evidence indicates disc degeneration (DD) might sometimes result from a very low-grade infection. Advances in microbiome techniques enable detection of bacterial DNA, suggesting possible infections. Chronic pain also correlates with higher body mass index (BMI) and an altered gut microbiome.
This project explores how the microbiome might influence LBP. It investigates LBP and BMI in TwinsUK participants with spine imaging and gut microbiome sampling. It also examines IVD samples from hospital patients undergoing spinal surgery. The hypothesis is that changes in the microbiome cause LBP. This is the first study to check for microbial DNA in the disc and identify its source by searching other anatomical sites for similar microbes.
2024 - ongoing
Timescale: 48 months
The relationship between diet, gut microbiome, exercise and sarcopenic obesity.
Sarcopenic obesity (SO) is a common geriatric syndrome characterised by a combination of sarcopenia (low muscle mass, reduced strength, and physical dysfunction) and obesity (excess fat), which can lead to various clinical complications. Its prevalence is likely to rise as populations age. Factors such as ageing, diet, and a sedentary lifestyle contribute to SO, although its exact causes are unclear. Twin studies offer insights into genetic and environmental influences on SO and may inform prevention and treatment strategies. This PhD uses data from over 3,000 TwinsUK twins and new data from 200 twins to examine modifiable risk factors like diet, the gut microbiome, and physical activity.
The PhD project will adopt a novel approach to (i) identify factors linked to SO using data from the extensively phenotyped TwinsUK cohort; (ii) examine how diet, exercise, and gut microbiome affect SO, utilising existing and new data; and (iii) assess SO's impact on quality of life through a mixed methods approach. The hypothesis is that diet, microbiome, and exercise differences influence the development of sarcopenic obesity.
2024 – ongoing
Timescale: 24 months
Changes in gut microbiome composition and links to frailty and inflammaging.
Frailty is a complex condition linked to increased healthcare needs, disability, and mortality, especially in older adults. It is characterised by issues such as a weakened immune system. Despite its clinical importance, the true mechanisms and causes remain unclear. The gut microbiome plays a vital role in regulating immune function, inflammation, metabolism, and neuroendocrine signalling—all of which are associated with frailty. Shotgun metagenome sequencing is an advanced technique that helps identify and analyse these microorganisms in detail.
In this research project, we will identify both the immediate and long-term molecular indicators and associations linked to frailty and chronic inflammation within a large population-based TwinsUK cohort. We will utilise existing shotgun metagenome data previously funded by the CDRF, along with new data obtained through independent funding. This will allow us to explore how frailty and ageing affect the composition and functions of the gut microbiome over time.
2025 – ongoing
Timescale: 36 months
Genetic Epidemiology of Inverse Comorbidity
The importance of genetic studies of inverse comorbidity lies in understanding how one disease prevents another, which could lead to new drug targets and insights into the molecular basis of complex diseases. Inverse comorbidity serves as a natural model for drug discovery: by understanding how one disease reduces the likelihood of another, we can identify potential targets.
This study hypothesises that genetic predisposition to one complex disease may protect against another, leading to inverse comorbidity. We aim to measure this in the general population and explore its genetic basis.
Knowledge of the extent of inverse comorbidity in the general population is limited, aside from a few known cases such as CNS and cancer, allergy and tuberculosis. We need a systematic investigation, surveying all available diagnoses to identify new cases.
We will start with the large publicly available UK Biobank dataset (around 500,000 participants) and validate findings in the Norwegian Patient Registry (about 5 million), TwinsUK (roughly 15,000), and other public datasets and electronic health records. For transcriptomic profiling, we will use freely available resources.
2026 - ongoing
Timescale: 12 months
Exploring heterogeneity in diet, menopause, and metabolic ageing resilience in women: Insights from the ZOE PREDICT 3 cohort
This project explores how diet may shape women’s experiences of menopause and their long-term metabolic health. Menopause affects women differently, yet advice is often “one-size-fits-all.” Using data from over 140,000 women in the ZOE PREDICT 3 study, we will examine how everyday eating patterns relate to symptoms such as hot flushes, sleep and mood changes, as well as measures of blood sugar, cholesterol and weight. We will use advanced data analysis to identify different health patterns across diverse groups of women. Our goal is to inform more personalised dietary guidance to support healthier ageing during and after menopause.
2026 - ongoing
Timescale: 12 months
Utilising microbiome metabolomics to understand how bacterial folate status may drive ageing.
We want to know whether folate made by gut bacteria affects human health and ageing. Many gut bacteria make folate. Reducing this bacterial folate in laboratory models can slow ageing and reduce harmful bacterial behaviour. In the lab, we will grow bacteria with carefully controlled folate levels and measure related metabolic changes to identify markers that reflect bacterial folate production. We will then use these markers in an existing dataset of 200 people to explore links between bacterial folate levels, age and health markers. This could inform safer supplementation and new strategies to improve healthy ageing.
2026 - ongoing
Timescale: 12 months
Use of GLP-1RAs and dual GLP-1/GIP receptor agonists in a longitudinal population cohort: epidemiological overview, molecular correlates, and health outcomes of injectable weight loss therapy use
Powerful incretin-based injectables such as semaglutide and tirzepatide are transforming weight loss and diabetes management, yet we know little about how they are used in the population or how they affect healthy ageing, especially after stopping. We will survey TwinsUK participants with a dedicated questionnaire to map who uses these medicines, which drugs and doses they take, for how long, and how they access them. We will assess how use varies among participants and what early changes are reported in weight, mood, muscle health, and side-effects. We will then link this to TwinsUK’s multi-omic and biobank resources to support longer-term studies.
2026 - ongoing
Timescale: 36 months
The exposome in TwinsUK: Defining the molecular and physiological signatures of environmental exposure in health and disease
Growing evidence links daily environmental exposures—chemical, biological, and social—to adverse health outcomes. Most are beyond individual control and require scientific evidence to justify regulation through public health policy. While epidemiological studies suggest disease risk connections, more evidence shows environmental exposures also impact biology at molecular and physiological levels, such as hormone disruptions and metabolic changes. These biological shifts, known as the "exposome," can help establish causality between environment and health.
TwinsUK's extensive data and samples enable large-scale exposome research. This project will explore how air pollution, housing, and infection history influence molecular and physiological markers, including the epigenome, transcriptome, metabolome, immune profiles, and sex hormones. Using NHS Digital EHRs and MRI data, we will assess whether environmental effects on health are mediated through the exposome. Defining the exposome in TwinsUK will reveal new biological pathways linking environment to health and disease, guiding public health policies and advancing precision medicine.
