Active Infection & Immunity Genetics & Molecular Biology

Tuning Immunity: Regulation and Functions of CaMKII at the Host-Pathogen Interface

Funder Wellcome Charity-funded
Recipient organisation King's College London
Funding £2.3M
Period Sept 2025 — Sept 2033

In plain English

AI plain-English summary

When a pathogen invades the body, a protein called CaMKII acts as a molecular switchboard operator, tuning the immune system’s inflammatory response—and this project will work out exactly how that switchboard works and how germs try to jam it. The problem is that while scientists know the broad outlines of how immune cells detect microbes and turn on defence genes, they have a much hazier picture of the fine-tuning signals that calibrate inflammation. CaMKII is a calcium-regulated kinase, meaning it adds phosphate groups to other proteins in response to calcium surges, and the researcher suspects it sits at a critical junction where host and pathogen battle for control. If CaMKII boosts immunity, then many pathogens may have evolved specific virulence factors to disable it. This is fundamental science. The work will map CaMKII’s activation dynamics, test its role in live infection models, and hunt for pathogen proteins that target it. Success would reveal new molecular handles for designing host-directed therapies—drugs that strengthen the immune system’s own response rather than killing microbes directly—and could open routes to antimicrobials that pathogens find harder to resist.

View original technical description
Globalisation has enabled greater social and economic exchange, but also the rise and spread of infectious agents. Understanding how pathogens cause disease and how our immune system responds to infections is an increasingly urgent challenge for human health. Precise regulation of immune signalling events and the integration of multiple signal transduction cascades are critical in the rapid establishment of an effective immune response. While canonical pathways linking microbial detection to transcriptional responses are well characterised, the specific molecular signals that fine-tune inflammatory signalling remain poorly understood. I propose that the calcium- regulated kinase CaMKII modulates inflammatory sensing and boosts immunity against pathogens. Further, I propose that the CaMKII axis is an evolutionarily conserved target for diverse pathogens seeking to evade host immunity. With this work I will 1-Determine the dynamics of CaMKII activation and how CaMKII integrates with inflammatory signalling; 2-Define the immune regulatory functions of CaMKII signalling using animal models of infection; 3-Identify and characterise virulence factors from diverse pathogens that antagonise CaMKII to evade immune detection. This research plan at the interface between host and pathogen will reveal new mechanisms of immune sensing and pathogenesis. This will identify biological targets for novel antimicrobial and host-directed therapies.

View the original record at the funder ↗

Researchers

Charlotte Odendall (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Mapping of the signalling pathways required for anti-fungal responses using global proteomics
Mechanisms and evolution of innate immune signalling activation across species
Host and bacterial factors that drive hypervirulence in multidrug resistant pathogen infection
Cytokine network ecology: towards a dynamic understanding of immune responses to co-infection
Interkingdom signalling: how Pseudomonas aeruginosa senses and adapts to the host environment.

Original classification

Career Development Award

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.