Descripción del proyecto
Superar el envejecimiento celular con nanocuerpos
Las células madre hematopoyéticas (CMH) pueden diferenciarse en múltiples linajes y autorrenovarse, lo que repone las células sanguíneas a lo largo de toda la vida. Cada vez hay más pruebas de que la inflamación crónica daña las células madre hematopoyéticas y provoca un envejecimiento prematuro. Curiosamente, las CMH envejecidas muestran una mayor expresión de marcadores plaquetarios y megacariocíticos y un compromiso sesgado a diferenciarse por la vía plaquetaria. El equipo del proyecto UNBIAS, financiado por el CEI, pretende restablecer una diferenciación equilibrada de las células madre hematopoyéticas. Para mitigar la inflamación, los investigadores proponen utilizar nanocuerpos que puedan borrar las memorias inflamatorias de las CMH. A diferencia de los anticuerpos convencionales, los nanocuerpos constan de una sola cadena polipeptídica y tienen un tamaño mucho menor, lo que les permite penetrar en los tejidos y unirse firmemente a objetivos específicos.
Objetivo
"With a growing ageing population, there is an imminent demand to develop new therapeutic strategies to ameliorate disorders of the hematopoietic system. Our innate immune system can remember its previous encounters with inflammatory triggers. Epigenetic memories of previous inflammatory experiences throughout an individual's lifetime are imprinted in hematopoietic stem cells (HSCs), a small pool of bone marrow progenitors that give rise to all our blood cells. Inflammation harms HSCs causing their functional decline and premature ageing. It also causes long-term differentiation bias, and a heightened basal inflammatory status, known as “inlfammageing”. The most striking characteristic of aged HSCs is their increased expression of platelet and megakaryocyte markers and their commitment towards platelet biogenesis, referred to as “Platelet-bias."" Platelet bias has important consequences to human health. In our ERC starting grant project PLAT-IL-1 (714175), we discovered that platelets boost the inflammatory capacity of innate immune cells and are essential for the cytokine production of human monocytes. Our findings support that a dangerous combination of myeloid and platelet bias in inflammation-exposed HSCst results in a heightened innate immune activation. The injuries to HSCs are persistent and continue even after the clearance of the inflammatory insult, indicating that remnants of inflammatory events accrue and prolong damage to HSCs. Hence, if we could “erase"" these harmful remnants, we could UNBIAS HSCs differentiation and prevent hyper-inflammation. In our ERC-funded project, we developed novel nanobodies that efficiently eliminate remnants of inflammation in vivo. In this PoC project, we will test the ability of nanobodies to erase memories from previous inflammatory events and prevent hyper-inflammation. This project will be a stepping stone to licensing our nanobodies to industrial partners."
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Convocatoria de propuestas
(se abrirá en una nueva ventana) ERC-2023-POC
Consulte otros proyectos de esta convocatoriaRégimen de financiación
HORIZON-ERC-POC -Institución de acogida
53127 Bonn
Alemania