IMPACT
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High Dimensional single cell mapping of inflammatory disease signatures in monoz...
High Dimensional single cell mapping of inflammatory disease signatures in monozygotic twins
Multiple Sclerosis (MS) is a chronic inflammatory disease, where immune cell invasion into the central nervous system causes immunopathology and neurological deficit. Although disease-modifying therapies dramatically reduce diseas...
Multiple Sclerosis (MS) is a chronic inflammatory disease, where immune cell invasion into the central nervous system causes immunopathology and neurological deficit. Although disease-modifying therapies dramatically reduce disease activity, they hold the potential for severe adverse effects while long-term disability prospects remain poor. Moreover, there is to date no biomarker for monitoring the disease activity and to guide therapy decisions. I propose that the key to identifying such biomarkers is to combine single-cell mapping of leukocytes across well-curated patient cohorts with unbiased machine-learning based data interrogation. Using such an approach, we have already delineated a disease signature in a helper T cell population specific for MS. However, the immune compartment of cross-sectional cohorts is influenced by the individual genetic make up, which masks disease-specific signals and hinders a more precise characterisation of involved immune cell populations. To eliminate genetic influences, I here propose in aim 1 to interrogate the immune compartment of a unique cohort of monozygotic twin pairs -discordant for MS- and deeply analyse peripheral blood lymphocytes by single-cell mass cytometry, combined TcR and single cell sequencing, and epigenetic profiling. aim 2 to develop representation-learning methods to account for the paired genetics of twins or longitudinal samples and to include clinical covariates into the high-dimensional data set. aim 3 to use well-defined patient samples of MS-like disorders (MS-Mimics) and longitudinal samples of patients undergoing disease-modifying therapy (e.g. B cell depletion, autologous stem cell transplant) using single-cell mass cytometry. Ultimately, the goal is to reduce the dimensionality of disease signature(s) towards a clinically translatable low-dimensional biomarker that could be identified and quantified by routine methods available in the clinics.
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Duración del proyecto: 77 meses
Fecha Inicio: 2020-07-29
Fecha Fin: 2026-12-31
Fecha Fin: 2026-12-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2020-07-29
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2019-ADG:
ERC Advanced Grant
Cerrada
hace 5 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
UNIVERSITAT ZURICH
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
541.38K€ |
Participante