Projektbeschreibung
Mitochondrien bei seltenen Immunerkrankungen
Interferone bilden die erste Abwehrfront gegen Viren. Bei einer seltenen Gruppe genetischer Erkrankungen, den Typ-1-Interferonopathien, ist die Interferonsignalgebung überaktiviert. Der Nukleinsäurestoffwechsel und die Mitochondrien scheinen die Interferonsignalgebung auszulösen und könnten daher als neue therapeutische Targets für Typ-1-Interferonopathien in Frage kommen. Das EU-finanzierte Projekt MitoFeron wird ein Mitochondrienprotein erforschen, das an der verstärkten Interferonsignalgebung bei an Typ-1-Interferonopathien Erkrankten beteiligt ist, und seine Rolle bei der Organellenhomöostase und Interferoninduktion abgrenzen. Mit den Ergebnissen werden sich ein neues klinisches Screeningprotokoll für Patientinnen und Patienten mit Typ-1-Interferonopathien sowie neue Targets für die therapeutische Intervention entwickeln lassen.
Ziel
Type I interferonopathies (T1IFNs) are rare genetic diseases associated with an inappropriate upregulation of type I interferon (IFN) signalling. IFNs represent the first line of defence against viruses, and are induced by sensing of viral nucleic acids. Definition of the genetic basis of the T1IFNs has led to a coherent understanding of underlying pathology, involving previously unappreciated pathways of nucleic acid metabolism, and enabled the introduction of rational therapy targeted at blocking IFN signalling. Thus, it is important to identify new T1IFNs and determine their molecular and cellular basis.
Beyond their role in energy metabolism, mitochondria are also recognised to play a role in the immune response to infection. Interestingly, both mitochondrial (mt) DNA and mtRNA have the potential to trigger IFN. Indeed, loss of mt integrity promoting pathogenic IFN induction, through mt nucleic acids released into the cytosol, is a novel topic of high clinical and scientific interest. We have identified patients with mutations in a gene encoding a mt protein, in which we consider the observed enhanced IFN signalling directly relevant to the associated neuropathology. My project aims to better understand the link between mt homeostasis and IFN induction, thereby defining novel pathways relating to mt integrity, mt nucleic acids and innate immune surveillance. Specifically, I will study these relationships in the context of human disease, and I will search for further novel determinants of mt function linked to innate immune homeostasis using our unique clinical screening protocol.
I will bring my expertise in mt biology to the host laboratory. At the same time, this project will place me at the leading edge of clinically-directed research on nucleic acid sensing and autoinflammation. Thus, this training opportunity is designed to lead me towards independence through the acquisition of new skills and the discovery of novel research paths for my future career.
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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Koordinator
75015 Paris
Frankreich