Dr Signoret Joined the Hull York Medical School in 2006, arriving from the MRC-LMCB unit at University College London, to start her academic career in York.
Her research focus on a set of molecular sensors called chemokine receptors. These receptors are essential components of our immune system, coordinating host cell responses to infection and implicated in numerous pathologies, including cancer.
Her work investigates the functional regulation of these receptors to better understand their contribution to health and disease processes. Her work is truly interdisciplinary, collaborating with physicists and chemists to develop new tools and approaches to answer biological questions. In addition, she collaborates with clinical teams from York and Hull NHS Teaching Hospitals for translational studies investigating chemokines and their receptors as potential disease biomarkers.
In addition, Dr Signoret is involved in Hull York Medical School Phase I teaching, teaches for the University of York Biomedical Sciences BSc programme in the Department of Biology, and engages in post-graduate students supervision.
She has administrative roles within Hull York Medical School acting as Chair of the Board of Examiners for the MBBS programme and being a member of the HYMS Ethics committee. She is also part of the Biology Biomedical Science (BMS) exam committee.
She is active in the national and international research community and currently sits on the committee of the British Society for Cell Biology acting as Membership secretary.
Nathalie Signoret is a Senior Lecturer in Immunology. She obtained her undergraduate and master degrees as well as her PhD in Immunology from the University of Aix- Marseille II (France). During her PhD, she studied the role of the glycoprotein CD4 in HIV infection in the group of Prof. Quentin Sattentau at the Centre d’Immunologie de Marseille-Luminy (CIML). Nathalie then moved to the MRC-LMCB in London for a post-doc with Prof. Mark Marsh where she developed her interest in chemokine receptor biology. She remained in the group of Prof. Marsh at the MRC-cell Biology Unit as a senior research associate until 2005, investigating the molecular mechanisms regulating CXCR4 and CCR5 surface expression and intracellular trafficking. In 2006 Nathalie was appointed Lecturer in Immunology at Hull York Medical School and established her group in York as part of the IIU.
Career
- University of AIX-Marseille II, France
BSC in Life Sciences 1989
Master in Immunology 1991
PhD in Immunology 1996
- MRC-LMCB, London
Marie Curie Postdoctoral Fellow (1996 - 1999)
Postdoctoral Researcher (1999 - 2001)
- MRC-Cell Biology Unit, London
Senior Research Associate (2001 - 2005)
- Centre for Immunology and Infection
Lecturer in Immunology (2006 - 2017)
- Centre for Experimental Medicine and Biomedicine
Senior Lecturer in Immunology (2017 - )
Nathalie is a member of the Experimental Medicine and Biomedicine research group.
Research
Chemokine receptors
Chemokines and their receptors have emerged as essential controls for the trafficking and activation of immune cells, in both homeostatic and inflammatory conditions. Our research aims to define how these molecules influence immune responses and establish the mechanisms by which they exert their activity.We are particularly interested in the cell biological mechanisms mediating chemokine receptor functioning. Using primary human cells, we aim to identify the molecular pathways involved, as well as the molecular mechanisms regulating these different events. By extending our investigations to pathological situations (e.g: HIV/AIDS, bacterial Sepsis, COVID-19 and cancer) we aim to obtain a better understanding of the process of inflammation, and to identify targets for new anti-inflammatory therapy.
We discovered that modulation of cell surface receptors is a significant mechanism to control the cellular response to chemokine stimulation, which can differ between cell types. We demonstrated that the processes of internalisation, intracellular transport and recycling can 1) regulate the functioning of chemokine receptors; 2) modulate immune cell migration and response to bacterial infection; 3) control the ability of HIV to enter target cells.
Technologies
The lab uses a combination of immortalised cell-lines, human peripheral blood samples and in vitro culture of blood-isolated white blood cells as a model system. Projects require application of cellular, molecular as well as biochemical approaches using a broad range of techniques, with prevalence of flow cytometry, confocal & TIRF microscopy, pull-downs with western blotting, molecular cloning for cell transfection, and cell-based functional assays.
Projects
1- Regulation of CC chemokine receptors on T cells and monocytes:
Recruitment of activated T cells and monocytes to sites of inflammation is critical for the development of a protective immune response and elimination of pathogens. This process is governed by the ability of chemokines secreted in the inflamed tissue to attract T cells and monocytes towards the source of infection where they carry out their immune cell duties. Our project aims to elucidate the mechanisms controlling chemokine receptor expression and regulation on T cells versus monocytes and establish how they influence immune responses.
2- CC Chemokine receptors membrane mobility and interacting partners:
The distribution of chemokine receptors at the surface cells is tightly controlled by the cellular machinery from regulators of membrane transport and cytoskeleton to signalling and membrane components. The goal of this project is to identify new interactions influencing the behaviour of the CC chemokine receptor CCR5 at steady state or upon chemokine stimulation and cross-regulation via other surface receptors.
3- CCR5 and the Immunological synapse:
We have shown that during the formation of an immunological synapse (IS) for contact-based communication between a CCR5+ T cell and a macrophage, CCR5 receptors move to the cells interface. Using Live microscopy coupled with single molecule tracking technology, we are now studying the dynamic behaviour of CCR5 molecules, to understand the meaning of their relocation in IS.
4- Chemokines and chemokine receptors blood profiles associated with human infections:
Changes in chemokine receptor expression by immune cells and chemokines levels in blood circulation have been documented for many diseases, but the physio/pathological significance of these changes remain unclear. Using flow cytometry-based assays we are investigating whether the chemokine system could reveal specific biomarker signatures to diagnose severe infections.
MBBS: Phase I teaching: lecturing year 1 students in the foundations to medicine block, and teaching SSIP in the EMB group.
Biomedical Sciences BSc programme in the Department of Biology:Act as pastoral supervisor for BMS students throughout their degree, co-lead and teach the year 2 Biomedical Sciences skills practicals, teach Virology in the year 3 module "pathogens and pathogenesis", and supervise BSc group research projects.
Visit Dr Nathalie Signoret's profile on the York Research Database to see a full list of publications, browse activities and projects, explore connections, collaborations, related work and more.
External examiner for BirkBeck Biomedical Sciences BSc , University of London (2018 - 2021)
Academic editor for PLoS One (2011 - 2021)
External examiner for research degrees Mres & PhDs (acted in UK and Europe)
Membership Secretary of the British Society for Cell Biology (BSCB since 2024)