RAPID-KDM · Application of peptide screening technology for identification of substrates of the Jumonji-C histone demethylases
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2015-10-01 → 2018-09-30
- Финансиране от ЕС
- 270 272 €
- Участници
- 2
- Схема
- MSCA-IF-GF
Линиите свързват координатора с партньорите.
Накратко на български
Ензимите от групата Jumonji-C променят протеините в клетките, като например модифицират остатъците от аргинин. Разбирането на тези процеси помага при търсенето на нови лекарства срещу различни заболявания и нарушения в развитието.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Application of peptide screening technology for identification of substrates of the Jumonji-C histone demethylases
The functional human proteome is vastly expanded by post-translational modifications that modify protein function and gene expression in a time- and context-dependent manner. These are particularly important in the field of epigenetics – the study of changes in gene regulation not caused by changes in the underlying DNA sequence. Misregulation of these modifications correlates with a wide range of developmental disorders and disease pathologies, accounting for a high burden of disease and deaths in the EU. Enzymes that regulate post-translational modifications therefore represent key drug targets for both academics and the pharmaceutical industry. To successfully manipulate these enzymes and marks for therapeutic benefit it is essential that we understand their roles within a cell. Despite their great importance, the full roles and regulation of these modifications and epigenetic enzymes remain poorly understood. Modifications of arginine residues remain especially understudied. The overall scientific objective of this project is thus to develop screening methodology, based on cutting-edge mRNA-display-based screening technology (the RaPID system) developed by the Suga laboratory (University of Tokyo), to identify enzyme substrates. Additionally, the work aims to develop inhibitors/peptide probes for these epigenetic enzymes, which will serve vital functions both to further elucidate the functions of these proteins within cells and also to act as drug leads. To achieve these scientific aims, a major objective of this project is to provide the fellow with training in the state-of-the-art RaPID system and other advanced methodologies. Combined with the exposure to a different culture and language, and the opportunity to observe how research is conducted in another country, this fellowship will be invaluable in accelerating the fellow’s career trajectory on return to the EU.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
In recent years it has become evident that the functional human proteome is vastly expanded by post-translational modifications (PTMs) that modify protein function and gene expression in a time- and context-dependent manner. Misregulation of these modifications leads to developmental disorders and often contributes to disease biogenesis. However, with the possible exception of protein phosphorylation, the full roles and regulation of these modifications remain poorly understood. Currently, in particular, arginine methylation is proposed to be largely stable and irreversible. Building on my exciting preliminary data that demonstrate that Jumonji C histone demethylases (JmjC KDMs) can catalyse removal of arginine methylation, this proposal aims to identify biologically relevant methylarginine substrates of the JmjC KDM. Cutting-edge mRNA display-based peptide screening technology will be adapted for use as a substrate identification assay in collaboration with Prof Hiroaki Suga at the University of Tokyo. Consensus sequences identified using this novel methodology will be used to identify biologically relevant peptide sequences by bioinformatic searches. On the return to the UK, results with isolated proteins will be correlated with in-cell studies and the functional consequences of these reactions assessed. Given the high level of interest in the post-translational modification field, the results of this study will be of interest to a very wide-range of scientists including other academic researchers in the field of epigenetics and beyond, and major biotechnology and pharmaceutical companies studying JmjC KDMs as drug targets. The fellowship will provide training in state-of-the-art techniques. The collaboration between the University of Oxford and the University of Tokyo will enhance the research capabilities of the European Union, promote cross-fertilisation of knowledge and strengthen research ties with Japan.
Оригинален текст от CORDIS (на английски).
Участници
- THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OxfordКоординаторОбединеното кралство
- NATIONAL UNIVERSITY CORPORATION THE UNIVERSITY OF TOKYO · TOKYOЯпония
Връзки
Данни: CORDIS, © Европейски съюз