H2020Индивидуална стипендия2019–2021

qCHROMDEK · Quantitative insight into chromatin nanoscale structure: sub-nuclear organisation of oncoprotein DEK

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

Период: 2019-12-01 → 2021-11-30
Финансиране от ЕС: 171 473 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Протеинът DEK и неговото разпределение в ядрото на клетките при рак на гърдата се анализират чрез специална микроскопия. Разбирането на тези процеси помага да се установи как архитектурата на хроматина влияе върху развитието на заболяването.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Quantitative insight into chromatin nanoscale structure: sub-nuclear organisation of oncoprotein DEK

Chromatin organization is the fundamental feature of physiologically functioning eukaryotic cells and, when misbalanced, can cause severe pathological conditions such as cancer. Specific chromatin factors ensure the maintenance of chromatin architecture and the proper functioning of chromatin-related processes. One of such protective chromatin proteins is DEK protein, which plays an important role not only in nuclear processes but also in cancer biology. In recent years, the DEK protein gathered significant attention from the scientific community, thanks to its numerous functions and potential role within cancer progression – features that candidate DEK as a potential cancer biomarker. The cellular functions of the DEK protein are still a subject of ongoing research. So far, multiple studies have shown that DEK has a pleiotropic mode of action by influencing several regulatory pathways. The qCHROMDEK project aimed to investigate, via 4D advanced fluorescence microscopy, the correlation between the sub-nuclear organization of the DEK protein (connected to overexpression level differences in normal and cancer cells) and the local chromatin organization in a breast cancer model. In particular, the project’s goals include: (a) quantitative analysis of the correlation between DEK protein distribution and the pattern of specific post-translational histone modifications marking eu- or heterochromatin; (b) analysis of the above mention correlation along the process of cancerogenesis (represented by a breast cancer model of three cell lines – MCF10A, MCF7, and MDA-MB-231 cells); (c) the study of the DEK protein nuclear pattern along with the cell cycle progression; (d) the investigation of the role of DEK bodies in the process of the DNA replication; (e) and the connection between DEK bodies formation and the type of chromatin content.

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

Цел на проекта

DEK protein is a chromatin architectural factor which has been consistently associated with tumour progression. Its expression level differs between normal and cancer cells, raising the possibility of using DEK as a tumour marker. On the other hand, super-resolution imaging revealed recently that nucleosomes can form discrete groups called ""clutches"" of various dimensions and densities. However, the quantitative analysis of the connection between proteins playing chromatin architectural role and nucleosome clutches has not been yet deciphered.Within this project, I hypothesize that there is a correlation between the organisation of DEK oncoprotein and the local chromatin structure related to the proliferation level of cells.The overall aim of the proposed work is to provide a more precise, quantitative understanding of possible connection between DEK expression level and local chromatin structures and by that to gain the additional information about DEK role in cancer. This project will take advantage of cutting-edge biophysical tool such as DNA origami, single-molecule localisation microscopy and cellular biology. Experimental design is based on the construction and application of a bi-dimentional DNA origami to calibrate and mimic subnuclear structures. The quantitative approach will rely on STochastic Optical Reconstruction Microscopy (STORM). This study will be done using normal cells with different level of proliferation and cancer cells with different level of malignancy.Finding the relation between DEK expression, connected to the proliferation level of normal and cancer cells, and the number of nucleosomes per clutch could improve the comprehension of chromatin organisation role in different levels of tumorigenesis. Quantitative insight to the number of nucleosomes per clutch in relation to the level of cell proliferation could be in the future an input for a precise recognition of cancer in the early stage of tumorigenesis.""

Оригинален текст от CORDIS (на английски).

Участници

FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA · GenovaКоординаторИталия