Knight group

Functional genomics of immunity

Research overview

Our 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.

Local and distant associations with gene expression in human monocytes (Science 2014)

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.

Resolving heterogeneity in sepsis (Lancet Respir Med 2016)

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 team approach.

Funding sources

Wellcome Trust, Arthritis Research UK, Psoriasis Society, Oxford Biomedical Research Centre

Keywords

Keywords: Gene expression, regulatory variants, genome editing, MHC, immunity, inflammation, sepsis, transcription, single nucleotide polymorphism, ankylosing spondylitis, eQTL, functional genomics, epigenomics, drug targets

Our team

Julian Knight

Professor of Genomic Medicine
Alicia Lledo Lara

DPhil Student
Giuseppe Scozzafava

Research Scientist / Lab Manager
Dr Hai Fang

Postdoctoral Research Scientist
Bogdan Knezevic

DPhil Candidate
Julie Osgood

DPhil Student
Dr Cyndi Goh

DPhil Student
Dr Kate Elliott

Senior Postdoctoral Bioinformatician
Dr Andrew Brown

Postdoctoral Researcher
Dr Gabriele Migliorini

Postdoctoral Research Scientist in Statistical Functional Genomics
Dr Justin P. Whalley

Senior Postdoctoral Bioinformatician
Dr Lahiru Handunnetthi

Clinical Research Fellow
Dr Olga Mielczarek

Postdoctoral Researcher
Yuxin Mi

DPhil Student
Alice Allcock

Research Assistant
Dr Chwen Tay

Postdoctoral Research Scientist in Functional Genomics of Immunity
Dr Harindra Amarasinghe

Postdoctoral Research Scientist
Félicie Costantino

Visiting Fellow
Carla Cohen

Postdoctoral fellow
Andrew Kwok

DPhil student