HEИндивидуална стипендия2023–2025

SOADOPP · Supramolecular organization and dynamics of presynaptic proteins

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

Период: 2023-09-01 → 2025-08-31
Финансиране от ЕС: 189 687 €
Участници: 2
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Протеините в синапсите на мозъка се изследват чрез суперразрешаваща микроскопия, за да се види как се подреждат при предаването на сигнали. Това помага за разбирането на работата на мозъка и произхода на неврологичните разстройства.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Supramolecular organization and dynamics of presynaptic proteins

The human brain operates through trillions of connections, known as synapses. Neuronal cells communicate via these connections by releasing chemical messengers in a process that takes milliseconds. At the heart of this process is a sophisticated machinery of proteins that must assemble and act with nanoscale precision. However, the precise three-dimensional arrangement and rapid dynamics of these proteins have remained elusive for decades, hindering our understanding of healthy brain function and the origins of neurological disorders. The SOADOPP project aimed to overcome this fundamental barrier by developing and applying revolutionary super-resolution microscopy techniques. The project's overarching goal was to visualize the 3D supramolecular structures of the presynaptic protein machinery during neurotransmitter release with nanometer resolution. The project combined cutting-edge methods such as Metal-Induced Energy Transfer (MIET), DNA-PAINT and MINFLUX to provide an unprecedented view of this vital biological process.

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

Цел на проекта

Since the prophetic vision of the German scientist Emil du Bois-Reymond in 1877 that put forward the hypothesis of the chemical nature of synaptic transmission, a large number of biochemical, genetic and neuro-physiological studies have revealed all the components that are involved in synaptic vesicle (SV) exocytosis. This complex action-potential-triggered process, in which the entry of calcium ions (Ca2+) into the presynaptic compartment induces a milliseconds-fast fusion of neurotransmitter-containing SVs with the presynaptic plasma membrane (PM), requires a number of so-called presynaptic proteins playing different roles. To date, despite all the knowledge acquired about presynaptic proteins, the question how they carry out this fast process remains unanswered. Recently, it was hypothesized that the presynaptic proteins are organized in specific supramolecular arrangements and do cooperate to achieve this remarkable feat. However, the study of presynaptic protein arrangement and functioning at nanometer isotropic scale is challenging, and decades of research were unable to resolve this phenomenon. In this project, I plan to study the three-dimensional supramolecular structures of the presynaptic proteins during SV exocytosis at nanometer isotropic resolution, and its structural dynamics on the nanometer length scale with microsecond temporal resolution. For this purpose, I will combine the super-resolution technique Single-Molecule Metal-Induced Energy Transfer (smMIET), developed by the host group, with the single-molecule localization microscopy (SMLM) methods of DNA-PAINT and MINFLUX. The overall importance of this proposal in understanding the Ca2+-triggered SV fusion is that it is essential to understand how synapses and ultimately the brain work, and all derived knowledge and applications that comes with it.

Оригинален текст от CORDIS (на английски).

Участници

GEORG-AUGUST-UNIVERSITAT GOTTINGEN STIFTUNG OFFENTLICHEN RECHTS · GottingenКоординаторГермания
JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG · WuerzburgГермания