The Knight group
My research aims to understand how genetic variation impacts genes critical to mounting an appropriate immune response and may contribute to susceptibility to infectious, inflammatory and autoimmune diseases. There is a wide spectrum of genetic variation modulating inter-individual differences in immune response with functional consequences ranging from severe primary immunodeficiency disorders to risk of multifactorial traits involving inflammation and immunity. Our recent discovery that non-coding regulatory variants are major drivers of diversity in the immune response transcriptome identifies an important mechanism for this.
The disease relevance of regulatory variants is highlighted by genome-wide association studies (GWAS) in which the majority of reported associations have been found to involve non-coding variants. To take forward the results of GWAS and translate into potential clinical benefit, we now need to define causal regulatory variants, resolve their mode of action and identify the specific modulated genes and pathways which may be therapeutic targets.
Our goal is to leverage recent advances in human genetics to improve understanding of biological process in immune disease pathogenesis, validate drug targets and advance opportunities for precision medicine.
Our work combines bioinformatics with functional genomic approaches studying genetic variants in primary cells in disease relevant contexts and establishing mechanism. This includes analysis of allele-specific gene expression, expression quantitative trait mapping and detailed characterisation of how sequence diversity modulates the epigenetic and genetic control of gene expression.
We have established translational programmes in the genomics of sepsis as part of the Genomic Advances in Sepsis study and in ankylosing spondylitis.
We aim to promote use of genomics for drug target identification and validation, public engagement with genomics and implementation of genomic medicine in the clinic through education, training and a multidisciplinary approach.
Justin has a special interest in integrating genetic expression, protein abundance and cellular population data to better understand the varying response to infection, especially in COVID-19 and Sepsis patients. He currently works as a senior postdoc in the Knight group at the Wellcome Centre for Human Genetics, Oxford (2017 – present). He has previously worked as a post-doctoral fellow on the genetics of cancer and rare diseases at the Centro Nacional de Análisis Genómico in Spain (2014 – 2017) and as a doctoral student researching plant evolution at the Université d’Evry in France (2010 – 2014).
I am a postdoctoral researcher studying the host immune response during sepsis. Sepsis is a life-threatening condition caused by an uncontrolled response to infection, and it contributes significantly to the worldwide burden of infectious diseases. While advances in life support have reduced the mortality of this condition, our understanding of sepsis is incomplete and there is an urgent need for new treatment alternatives. In particular, sepsis is a heterogeneous condition, and patients could benefit from stratification into risk groups and personalised treatments. My research focuses on using high-throughout data to build reliable methods for precision medicine in sepsis. I am particularly interested in understanding which cellular alterations put patients at high risk and how these change over time.
I am working as a post-doctoral bioinformatician focusing on host-pathogen genomics. My current work focuses on how -omic variation in host and pathogen modulate the response to infection in the context of sepsis.
I received my undergraduate degree in Biomedical Sciences from the University of Portsmouth in 2011, I then worked for the NHS working in Clinical Research Governance. In 2014 I started began working on the NIHR Health Informatics Collaborative in Oxford which is a multi centre project with the aim of integrating clinical data from electronic patient records and using this for clinical research into viral hepatitis. I completed my DPhil in Professor Ellie Barnes’s group at the University of Oxford in 2020. My DPhil work was focused on the characterisation of Hepatitis C Virus anti-viral resistance.
As a clinician who’s worked in the best ICU of mainland China for the past few years, I understand some patients deteriorate very soon (hours) after developing severe infection or sepsis, during which organ failure might be presented and very few interventions can be done to reverse this process. Studying sepsis susceptibility and identifying patient clusters with specific pathophysiological mechanisms is key preparation for future targeted therapy in this acute illness.
I was awarded 2021 CSC-CAMS-Oxford Scholarship to do a Dphil project based in Knight Group to investigate dysregulated host immune response by multi-omic approach. Previous work from the group has defined sepsis response signatures as informative endotype associated with outcome and post-hoc analysis of VANISH trial also gave a hint that SRS2 patient group correlates with early mortality if managed with hydrocortisone. My major interest with the accessibility of intense training in Genomic medicine would be identify patient groups benefiting from steroids or early endpoints of fluid resuscitation and reveal underneath pathogenesis by multi-dimensional mobilities.
Sepsis is a life threatening condition with high morbidity and mortality and few therapeutic options. Understanding the biological basis of this deleterious host response to infection is the main aim of my research. I am looking to further our understanding of the cell type specificity underlying disease endotypes that the group has previously established through transcriptomic analyses of peripheral blood in septic patients. Methods involved will include immunophenotyping as well as transcriptomic and epigenetic analyses, in particular at the resolution of single cells.
I completed my pre-clinical medical training at the University of Cambridge before moving to clinical school in Hong Kong at the Chinese University of Hong Kong. After practising as a junior doctor, I was awarded the Nuffield Department of Medicine Prize Studentship and the Croucher Foundation Scholarship to join the Knight group and study for a DPhil in Clinical Medicine.
I completed a BSc in Bioveterinary Sciences and MRes in Canine genetics at the University of Lincoln, focusing on research relating to adverse drug reactions in Border collies and the impact of dog domestication on immune tolerance. Following on from this, I obtained a PhD from the Royal Veterinary College (RVC), graduating in early 2021, focusing on the genetic diversity of the poultry red mite (Dermanyssus gallinae) to aid in the development of novel control measures. I spent 6 months working on parasitology and host genetics within the parasitology team at the RVC, focusing on host response to Eimeria infection, the parasite causing coccidiosis in farm animals. Following this, I joined the Knight group in August 2021 as a post-doctoral researcher working on the functional genomics of COVID-19. I am currently involved in the COVID-19 vaccine immune genetics (COVIG) project which focuses on understanding how genetic variation can impact vaccine response.
I am a doctor trained in Melbourne, Australia, now in the second year of my DPhil in the Knight group. My project focuses on using epigenomics to understand the natural history of sepsis and the effect of immunomodulatory treatment. I also oversee the Sepsis Immunomics study, which prospectively recruits patients with sepsis from local hospitals. In Oxford I am a member of Merton College and supported by the Rhodes Trust.
PhD student studying functional genomics of sepsis in Julian Knight’s group at the Wellcome Centre for Human Genetics, Oxford.
Yuxin is working on characterisation of the sepsis proteome for identifying novel disease endotypes and potential biomarkers.
PhD student in Genomic Medicine and Statistics, co-supervised by Julian Knight and Rachael Bashford-Rogers at the Wellcome Centre for Human Genetics, Oxford.
Lauren’s PhD will focus on understanding the adaptive immune response to sepsis through sequencing of the B-cell and T-cell receptor repertoires.
As a research assistant in the Julian Knight group, I work on a number of different projects.
The main focus of my work is investigating the contributions of different cell types to the septic
state, using peripheral blood samples from septic patients, under Andrew Kwok. Sepsis is a disease
with high morbidity and reduced understanding in terms of therapeutics, the aim of this research is
to improve our functional understanding of the disease which can aid in therapeutic development.
The opportunity to work within this research group has allowed me to explore my interest in medical
biology. I completed my bachelors in Biology at Oxford Brookes University in 2018, with my research
project focused on the genetic causes of insecticide resistance, in Malaria mosquitoes. I then worked as part of the cell line development team at Orbit Discovery, a small therapeutic drug discovery start-up company in Oxford, where I developed skills in culturing and altering immortalised cell lines. I now look forward to where my research role at the Wellcome Centre takes me.
Alice is part of the team that handles sepsis patient blood to isolate cell types of interest. She focuses on investigating how sepsis patient cells behave differently by carrying out multiple functional assays particularly involving T cells. Alice joined the Knight group in 2017 after completing her undergraduate education in Biochemistry at the University of Bath.
Angie is a specialist registrar in Anaesthetics and an NIHR clinical research fellow specialising in pain medicine and recovery from major illness.
She has set up the patient and public involvement group for the Knight group’s Sepsis Immunomics study and works on public engagement for the group, including this website.
Our collaborators
Dr Emma Davenport, Davenport Lab, Wellcome Sanger Genome Campus
Dr Katie Burnham, Dr Wanseon Lee, Dr Niek de Klein, Alex Tokolyi, Thomas Vanderstichele, Dr Dhupal Patel, Nihil Milind from Davenport Lab
Professor Charles Hinds (Professor (Emeritus) and Consultant in Intensive Care Medicine, Intensive Care Unit, Barts and the London Queen Mary School of Medicine and Dentistry, London)
Professor Anthony Gordon (Chair in Anaesthesia and Critical Care at Imperial College and Consultant in Intensive Care Medicine based at St Mary’s Hospital)
Professor Julian Bion (Intensive Care Unit, Queen Elizabeth University Hospital, Birmingham)
Dr Stuart McKechnie, Consultant in Intensive Care and Anaesthetics, Oxford University Hospitals NHS Trust
Professor Adrian Hill (Wellcome Centre for Human Genetics, Oxford)
Dr Kenneth Baillie (Academic Consultant in Critical Care Medicine at the University of Edinburgh and Edinburgh Royal Infirmary)
Professor Mark Caulfield (Director, Genome Centre, Barts and The London Queen Mary’s School of Medicine and Dentistry, London)
Dr Paul A Holloway (Division of Investigative Science, Imperial College, London)
Dr Charles Mein (Genome Centre, Barts and The London Queen Mary’s School of Medicine and Dentistry)
Dr Alex Mentzer (NIHR Academic Clinical Lecturer, Infectious Diseases, University of Oxford)
Sepsis Science 