Investigating Caspase 4 and Toll-like Receptor 4 Modulation by Endogenous Cardiolipin in Health and Barth Syndromecore
CL-ImmunoDimmer · Horizon Europe grant · 2025-09-22–2027-09-21
EC contribution
Total cost
Beneficiaries
About the data
Source: CORDIS (official EU open data), Horizon Europe. Framework HORIZON · call HORIZON-MSCA-2024-PF-01 · scheme HORIZON-TMA-MSCA-PF-EF · topic HORIZON-MSCA-2024-PF-01-01. CORDIS record →
Objective
Barth Syndrome (BTHS) is a disease characterised by reduced production of unsaturated mitochondrial cardiolipin (CL) and increased production of abnormal CL with saturated chains. Chronic inflammation and increased vulnerability to infection are major contributors to mortality in BTHS patients. The connection between these immune dysfunctions and CL modifications is not understood. My research has shown that unsaturated CL inhibits caspase 4 (CASP4) and Toll-like Receptor 4 (TLR4). Moderate CASP4 and TLR4 activation by bacterial triggers is essential for antibacterial defence, while uncontrolled activation results in infection lethality and inflammatory disease. My preliminary data show that abnormal CL similar to the one found in BTHS patients does not inhibit CASP4, and saturated CL activates TLR4. These findings suggest that in health, unsaturated CL acts as a dimmer to fine-tune immune reactions, while in BTHS, this dimmer is compromised, resulting in immune dysfunction. To investigate this hypothesis, this proposal ideally combines my expertise in cardiolipin and mitochondria research with the host’s expertise in gene editing and live microscopy. Using well-established methodologies, we will deplete CL from monocytes and macrophages and study how this affects CASP4 and TLR4 activation. Moreover, I will characterise BTHS immune response through the analysis of inflammatory markers in patients’ plasma, and patients’ neutrophils, monocytes and macrophages CASP4 and TLR4 response. This will provide a deeper mechanistic understanding of inflammatory processes in both health and disease, potentially identifying CL, CASP4, and TLR4 as new targets for treating BTHS. While I will enhance the team’s multidisciplinary character and provide collaboration opportunities, I will be trained in cutting-edge techniques and get leadership and network opportunities crucial for my long-term goal of scientific independence.
Beneficiaries (1)
| Organisation | Country | Role | EC contribution | SME |
|---|---|---|---|---|
| THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE | UK | coordinator | €276,188 |
Get the EU Defence Funding Calendar — free
The full calendar of open EU defence and dual-use funding calls, sorted by deadline, updated nightly. Delivered with DFM Analysis, our weekly briefing on who is funding what in European defence.
Or browse all open defence & dual-use calls on the funding calendar →
Defence Finance Monitor is an analytical and informational product. Grant data is official CORDIS; the paid Annual Professional subscription is handled on DFM Analysis.