MPFP · Membrane protein dynamics and interactions
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2014-06-01 → 2016-05-31
- Финансиране от ЕС
- 309 235 €
- Участници
- 1
- Схема
- MC-IIF
Линиите свързват координатора с партньорите.
Накратко на български
Мембранните протеини и техните взаимодействия с липидите се анализират чрез примери като рецептора родопсин. Разбирането на тези процеси помага да се разбере как функционират жизненоважни механизми в живите клетки.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Membrane protein dynamics and interactions
Membrane proteins are important for virtually all aspects of life, but are difficult to study experimentally due to their physical properties related to their location in membranes. This grant was used to recruit the membrane protein expert Professor Judith Klein-Seetharaman, from the University of Pittsburgh, USA and retain her in the Division of Metabolic and Vascular Health at the University of Warwick. She used the funds to establish an interdisciplinary research program combining computational and experimental studies, looking at membrane proteins from both, structural and systems biology point of views. In the structural biology project, she investigated membrane protein folding by characterizing denatured states of the model system and G protein coupled receptor mammalian rhodopsin in molecular detail, in comparison to the archaebacterial membrane protein, sensory rhodopsin, in a collaboration with the University of Cambridge. Second, conformational changes in the interferon gamma receptors were studied using circular dichroism, fluorescence spectroscopy and cysteine biochemistry. Third, interactions of proteins with lipids were studied in detail, and unique properties of lipid binding sites on proteins were structurally characterized. Uniquely, protein dynamics was also identified to play a major role in binding. Fourth, lipid-lipid interactions were quantitatively modelled and biophysically characterized in a new collaboration within the Division. In the systems biology project, the predicted human membrane receptor interactome was experimentally validated in a new collaboration with the Chemistry department. Thus, the intended goal of knowledge transfer from her USA research to the University of Warwick was successful at all levels, from initiation of new collaborations in the UK and within the University and Division, to publication of exciting scientific results. Beyond immediate research activities, she also conducted broader impact, education and outreach activities, ranging from disseminating her work in lecture series, conferences, a website, journal publications and through design and implementation of a Master class to conducting outreach activities in local schools and Science Fairs (Skirting Science, Big Bang Fairs) and by founding a local, active chapter for the national organization, ScienceGrrl, to promote women in science.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Many important protein families such as signaling receptors, ion channels, structural proteins and enzymes are embedded in the membrane of cells. Despite their importance, understanding of their structure, dynamics and interactions lacks behind that of soluble proteins due to their hydrophobic nature which makes them difficult to study experimentally. We propose to recruit and retain in the Division of Metabolic and Vascular Health at the University of Warwick, Judith Klein-Seetharaman, membrane protein expert from the University of Pittsburgh, USA. In an interdisciplinary approach combining computational and experimental studies, she looks at these proteins from both, structural and systems biology point of views. She proposes to study membrane protein folding by characterizing denatured states of the model system and G protein coupled receptor mammalian rhodopsin in molecular detail by predicting these states and experimentally validating them with biophysical approaches such as 19F NMR spectroscopy. She will extend these studies to mutant rhodopsins that cause the retinal degeneration disease Retinitis pigmentosa and that are known to misfold and to other membrane proteins, in particular carnitine palmitoyltransferase 1A, of particular interest to our division. She will also investigate interactions of proteins with lipids using coarse grained simulations and in a systems biology approach interactions with other proteins to define the human membrane receptor interactome by establishing new collaborations within the division and with the Chemistry department. In this approach, computational machine learning methods are used to integrate large –omics databases to predict what interactions are likely for any given membrane receptor and then test the predictions using surface plasmon resonance and the TOXCAT assay. She proposes to disseminate her results in lecture series, conferences, a website, journal publications and through implementation of a graduate course.
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSITY OF WARWICK · COVENTRYКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз