H2020Индивидуална стипендия2019–2021

TFs-HSCs · The identification of the Combinatorial Transcription Factor network exerting different roles in Hematopoietic Stem Cells.

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

Период: 2019-06-01 → 2021-05-31
Финансиране от ЕС: 212 195 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Мрежите от протеини, наречени транскрипционни фактори, регулират как кръвните стволови клетки се развиват и умножават. Разбирането на тези процеси помага да се разбере защо грешките в тях могат да доведат до развитие на рак и други 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

The identification of the Combinatorial Transcription Factor network exerting different roles in Hematopoietic Stem Cells.

Transcription factors (TFs) are the proteins which bind DNA and have many roles. Among others, they regulate transcription and control various important biological processes. Our genome has ~22,000 genes, with ~1,400 encoding TFs. In most of the cases, TFs exert their functions by forming networks, termed as transcriptional-regulatory-networks (TRNs). However most of the studies have been focused on some TFs and their functions in biological processes like generation of the blood cells from the hematopoietic stem cells (HSCs), generation/expansion of HSCs and differentiation of embryonic stem cells (ESCs). ESCs are pluripotent cells that can generate all cell lineages, whereas HSCs can give rise to the different types of blood cells. The ramifications of inappropriate regulation of gene expression controlled by the TFs in such cell types can be in various levels; from no effect on the cells up to inappropriate behaviour of the cells leading to diseases and cancer. Hence, it is important to uncover all the uncharacterized TFs as well as the TRN involved in such processes (like maintenance and differentiation of HSCs) and decipher their role.

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

Цел на проекта

Deciphering the TF network regulating hematopoietic stem cells (HSCs) would be important in treating acute myeloid leukemic (AML) patients; a rapidly progressing hematopoietic malignancy with poor prognosis and survival rate. Hematopoiesis is the process of generating all the mature blood cells from HSCs. Its regulation is, even until now, not fully understood and studied in all its levels. HCSs and hematopoietic differentiation are the key elements that are regulated by the cellular environment (extracellular/intracellular signals) funnelled into transcription factors (TFs). Notably, the human genome contains ~22000 genes estimating to encode 1391 TFs. I have already identified 420 TFs expressed in HSCs. Until now 20-30 TFs have been well-characterized in hematopoiesis, and my aim is to identify the role of the uncharacterized TFs required for hematopoiesis. First I will identify which of the 420 TFs have an effect in HSCs in vitro (WP1). Then I will test in vivo, if the TFs identified in vitro will affect hematopoiesis (WP2). Finally, I will investigate the functional properties of the selected TFs and unravel their role in chromatin organization and regulation of hematopoiesis (WP3). For all this, I will use novel state of the art methods like CRISPR/Cas9 and T2C. The accomplishment of my aims will provide new insights into how TFs regulate the generation/proliferation of HSCs.The proposal builds on my experience in data analysis, transcriptional regulation, chromatin architecture and the unique resources available at BRIC. Prof Helin, a world leading expert in hematopoiesis and cancer, and his lab have extensive experience on genetic screenings and molecular biology ensuring a successful outcome. Through this project, I aim to broaden/strengthen my expertise by acquiring the necessary technical/transferable skills assisting my future career progression to an independent researcher in the fields of molecular biology, chromatin architecture and hematopoiesis.

Оригинален текст от CORDIS (на английски).

Участници

KOBENHAVNS UNIVERSITET · KOBENHAVNКоординаторДания