Immunogenomics - Immune responses against infection. Using genomics, imaging and computational tools, we seek to understand the checkpoint mechanisms that ensure tailored immune responses against different infections in distinct tissues. Our long-term goal is to understand the intracellular and extracellular mechanisms that shape the architecture of the immune response against infection.
Reproductive atlas - Reconstructing dynamic maps of reproductive organs. As part of the Developmental Atlas in partnership with the Human Cell atlas, we are seeking to produce a comprehensive 3D cellular map of the reproductive system.
Cellular networks - Cell-cell communication. We aim to create an interactome map that will help us understand the basic mechanisms of cellular responses and functions, by mapping all interactions between the receptors on cells' surfaces and the ligands they bind, along with their downstream signals. To acheive this we are developing new approaches using single-cell and spatial transcriptomic data.
Immune responses against infection
Immune cells are spread throughout the body’s tissues and in circulation where they defend against infection and injury and contribute to homeostasis. Their response adapts to the specific challenges faced in different tissue environments.
One of the most intriguing environments is the maternal-fetal interface during pregnancy. Here, an appropriate immune cell response guarantees peaceful co-existence of fetal and maternal cells whilst also protecting against infection that may threaten the developing fetus.
Questions we aim to address:
What drives divergent immune responses against pathogens in unique, specialised peripheral tissues?
What detrimental effects does an imbalanced immune response have on fetus and mother during pregnancy?
What are the mechanisms involved in the transmission of viruses from mother to fetus (vertical transmission)?
Our lab uses genomics, imaging and computational tools to understand the checkpoint mechanisms that ensure tailored immune responses against different infections in distinct tissues. Through international and local collaborations, we have access to large cohorts of individuals and state-of-the-art in vitro co-culturing systems. Our long-term goal is to understand the intracellular and extracellular mechanisms that shape the architecture of the immune response against infection.
Reconstructing dynamic maps of reproductive organs
Sexual reproduction depends on the fusion of gametes (sperm and eggs) during fertilisation followed by implantation of the resulting embryo in the lining of the womb (the endometrium). Cellular decisions made in the early stages of embryo development will determine cellular diversity and their organisation in complex tissues and organs.
The majority of tissues will continue their development and maturation in adult life where they establish contact with the external environment. One exception to this principle is the placenta. The placenta is a unique transient organ that protects the fetus against external insults whilst providing it with nutrients.
Placental defects are associated with fetal growth restriction, miscarriages and preeclampsia, reflecting the crucial role of this organ in fetal development and maternal health.
Questions we aim to address:
What alterations in the maternal-fetal communication are associated with placental defects?
What cellular decisions made in early development shape cellular differentiation and tissue organisation?
What external and internal signals regulate the division and maturation of the gametes?
We use genomics, imaging and computational tools to produce a comprehensive 3D cellular map of the reproductive system. Our lab is part of the Developmental Atlas in partnership with the Human Cell Atlas.
The complex intracellular signalling pathways that drive cellular differentiation and function start with the binding of a signalling molecule (the ligand) to its receiving molecule (receptor). Mapping the ligand-receptor interactions during development, childhood, adult life and ageing is crucial to understand and predict cell identity and response.
In addition, an encyclopaedia of cell surface ligand/receptors interactions in both fetal and adult tissues is of huge interest for the design of novel targeted therapies, as these classes of proteins can be targeted by biologics.
Relevant interests in our lab:
What are the signals initiated by different ligand-receptor interactions?
Can we predict new extracellular and intracellular pathways using single-cell and spatial transcriptomics data?
Can we systematically map all the interactions of the body?
In collaboration with other experimental and computational teams at the WSI and EBI, we are currently developing new methods to link the receptor-ligand interactions with intracellular pathways and transcription factor activities using single-cell and spatial transcriptomic data.
By mapping all the ligand-receptor interactions and their downstream signals in different fetal and adult tissues we aim to create an interactome map that will help us to understand the basic mechanisms of cellular responses and functions.
Join our group
We are looking for motivated students and postdocs to join our group. We offer a friendly, collaborative atmosphere and direct one-to-one supervision.
We are based at the Wellcome Sanger Institute and collaborate with the EMBL-European Bioinformatics Institute (EMBL-EBI), our close neighbour. All members of the group will work together and have the opportunity to develop their experimental and computational analysis skills and experience.
The International Human Cell Atlas initiative aims to create comprehensive reference maps of all human cells—the fundamental units of life—as a basis for both understanding human health and diagnosing, monitoring, and treating disease.
We explore the consequences of genome variation on human cell biology, and thus gene function in health and disease. We conduct large-scale systematic screens to discover the impact of naturally-occurring and engineered genome mutations in human iPS cells, their differentiated derivatives, and other cell types.
The group seeks to elucidate the principles of protein structure evolution, higher order protein structure and protein folding, and the principles underlying protein complex formation and organization. We have a longstanding interest in understanding gene expression regulation, and in our wetlab at the Sanger Institute use mouse T helper cells as a model of cell differentiation.