H2020Индивидуална стипендия2019–2021

GPCR Transcriptomics · Exploring the role of GPCR expression diversity in receptor physiology and drug response

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

Период: 2019-05-01 → 2021-04-30
Финансиране от ЕС: 212 934 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Протеините-рецептори (GPCR), които улавят сигнали като светлина или хормони, се анализират чрез компютърни данни, за да се разбере защо един и същ рецептор реагира различно при различни хора или тъкани. Това помага за разработването на по-ефективни лекарства с по-добри терапевтични профили.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Exploring the role of GPCR expression diversity in receptor physiology and drug response

G protein-coupled receptors (GPCRs) are a family of membrane proteins involved in the detection of extracellular signals such as light, odour, metabolites, neurotransmitters and hormones. In parallel with their importance as sensors of a range of extremely diverse signals that reach human cells and tissues, GPCRs are also the target of the majority of drugs available in the clinic. However, despite their importance in the detection of environmental cues, cell to cell communication and drug action, there are still several unresolved questions on receptor function that hamper our ability to fully understand their mechanisms of action. One of these questions is related to the fact that activation of the same receptor can lead to differential signalling responses depending on the cell, tissue or individual that is being studied. These discrepancies in receptor signalling can make it difficult to translate measurements in cells and model organisms to humans, to develop new GPCR drugs with improved therapeutic profiles, and to explain variability in receptor function across the population. The overall objective of this project was to apply data-driven computational analyses to determine how changes in receptors at the cell, tissue and individual level could lead to a diversification of GPCR signals.

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

Цел на проекта

G protein coupled receptors (GPCRs) are key regulators of cell homeostasis. Given their importance in cell physiology, they have been extensively exploited as drug targets. Despite this, many discordant observations on receptor signalling and on GPCR drug response remain unexplained. Changes in receptor expression in different human tissues can be a key contributor to such differences in GPCR behaviour. And still, no comprehensive study has characterized human GPCR transcriptomics and its impact on receptor function. Such an analysis could help answer fundamental questions on GPCR pharmacology such as: How are different receptor types distributed across human tissues and how does this affect receptor function? How does age and gender-related GPCR differential expression affect receptor pharmacology? And how does splice variant distribution in different tissues influence receptor signalling? In this project, I will address these questions by applying a computational biology approach combining publicly available transcriptomics data with information on receptor structure, intracellular coupling, and pharmacogenomics. This will allow obtaining for the first time a GPCR-wide distribution map across human tissues; determining how differential expression according to age and gender can affect GPCR function; and assessing the impact of alternative splicing on receptor integrity, regulation, and coupling. At the end of this project, these insights will be made publicly available to the research community through the development of a web resource associated with the widely-used GPCR database. Using such a multidisciplinary approach, the proposed analysis will help clarify the importance of different receptor transcriptional profiles in cell physiology and drug response, point to more relevant systems to study GPCR signalling and to characterise new drug candidates, and foster a more personalised medicine by considering expression variability in the general human population.

Оригинален текст от CORDIS (на английски).

Участници

UNITED KINGDOM RESEARCH AND INNOVATION · SWINDONКоординаторОбединеното кралство