H2020Индивидуална стипендия2019–2021

COR1-TCELL · Analysis of the role for coronin 1-dependent cell density signalling in T-cell homeostasis

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-01-01 → 2021-03-02
Финансиране от ЕС: 175 420 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Ролята на протеина коронин 1 при оцеляването на Т-клетките се анализира чрез модел с мишки. Разбирането на този механизъм помага за разработването на по-безопасни и ефективни имунотерапии при рак и автоимунни заболявания.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Analysis of the role for coronin 1-dependent cell density signalling in T-cell homeostasis

Regulation of immune cells is a fundamental problem not only in infectious diseases or autoimmune diseases but also in cancer immunotherapy, for which European countries have invested and developed as one leading edge of the world. Therefore, gaining new knowledge on how to control the cell death and cell survival of immune cells, particularly T cells as a central control of the immune system in our bodies, will support further development of safe and efficient immune therapies. The main goal of the project was “to identify a molecular pathway mediated by coronin 1 that regulates peripheral T-cell homeostasis,” conducted by the researcher in the field of immunobiology, utilising a mouse model which shows unwanted T cell death by a lack of coronin 1 gene.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Harnessing T-cell homeostasis is important for cancer immunotherapy as well as anti-microbial immunity and the prevention of autoimmune disorders. T-cell homeostasis in peripheral lymphoid organs is known to be regulated through interleukin-7-mediated cytokine signalling and via T-cell receptors recognising self-peptides loaded on major histocompatibility complex. However, recent results suggest a requirement of a third pathway at low T-cell density such as in newborns that depends on the WD repeat protein family member coronin 1, the mechanism of which is unknown. The objective of this proposal is to elucidate the molecular mechanism of coronin 1-dependent sensing of low cell density that contributes to peripheral T-cell homeostasis.In preliminary work, I established a co-culture assay of T cells and antigen presenting cells that recapitulates coronin 1-dependent T-cell survival at low cell density. In addition, I found that adoptive transfer experiments reconstituted the coronin 1-dependent peripheral T-cell expansion in a lymphopenic environment in vivo. To delineate the molecular mechanisms underlying this cell density-dependent signalling mediated by coronin 1, I will combine the originally established in vitro and in vivo assay systems with state-of-the-art single-cell RNA sequencing, in addition to biochemical analysis utilising mass spectrometry. This will identify the signalling pathways and the molecules involved in this density-sensing mechanism. Finally, ad-hoc ablation of coronin 1 using a newly established inducible knockout mouse will reveal the role for coronin 1 in the maintenance of peripheral T cells after successful expansion at post-neonatal stage.The results from this project will define a hitherto uncharacterized density-sensing pathway required for T-cell homeostasis. Furthermore, the fellowship will potentiate my career opportunities as it allows to explore cutting-edge biology and technologies in a highly stimulating research environment.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITAT BASEL · BaselКоординаторШвейцария