H2020Индивидуална стипендия2019–2021

MetD-AO · Methyl Donating artificial organelles to support liver cells in Non-alcoholic fatty liver disease

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

Период: 2019-09-01 → 2021-08-31
Финансиране от ЕС: 219 312 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Изследват се изкуствени наночастици, които имитират работата на органелите в черния дроб за възстановяване на липсващи антиоксиданти. Това помага за разбирането как синтетичната биология може да намали токсичното окисление при мастност на черния дроб.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Methyl Donating artificial organelles to support liver cells in Non-alcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world, encompassing a spectrum of liver damage. Multiple issues are involved on the cellular level in failing liver often involve enzyme deficiencies, and the accumulation of reactive oxygen species (ROS) and reduced levels of glutathione (GSH). In healthy individuals, GSH is present in high levels in liver cells, playing a key role in removing ROS. In fatty liver cells, the missing antioxidant together with high ROS levels presents a toxic combination further pressuring the injured organ. NAFLD is recognized as an emerging medical challenge, and alternative concepts as potential medical interventions are highly sought after. Therefore, the findings of my fellowship contribute to the fundamental understanding how bottom-up synthetic biology can contribute to address biomedical challenges with the aim to provide a solution for affected individuals in the society. The goal of my fellowship was to explore a bottom-up synthetic biology approach eventually aiming at efficiently replenishing deficiencies in the liver. The overall objective included the design of polymeric GSH reductase activity mimicking polymer nanoparticles as artificial organelles (AO). AOs are typically nano-sized single compartment reactors, aimed to perform a specific encapsulated biocatalytic reaction within a cell to substitute for missing or lost function. AO design involves several challenges such as to have an appropriate carrier system, an adequate enzymatic reaction and the ability to be transported into the cytosol of the cell.

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

Цел на проекта

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world, encompassing a spectrum of liver damage. Multiple issues are involved on the cellular level in failing liver often including enzyme deficiencies such as reduced biosynthesis of S-adenosylmethionine (SAMe). Preserving SAMe homeostasis has only recently started to be considered as a potential therapeutic target in liver-related medical conditions. However, employing the required enzyme, SAMe synthetase (SAMe-synth), as a pharmaceutical, is challenging due to the general issues involved in intact (functional) protein delivery.The aim of the MetD-AO project is to assemble organic SAMe-synth activity mimicking polymer nanoparticles as artificial organelles (AO) and their in vitro characterization of intracellular function in hepatocytes. AOs are typically nano-sized single compartment reactors, aimed to perform a specific encapsulated biocatalytic reaction within a cell to substitute for missing or lost function. The AO will be based on amphiphilic copolymers consisting of a methyl-donating unit, cholesterol methacrylate and poly(5-carboxypentyl acrylate) as membranolytic hydrophilic tail. The latter two will aim at facilitating self-assembly and lysosomal escape, respectively. To allow structurally intact AO to escape the lysosome is unique since typically, the carrier is destroyed and only the therapeutic cargo is release into the cytosol. The proposed AOs with methyl-donating ability are highly advanced because the few prior reported AOs with intracellular activity all considered reactive oxygen related aspects at best. The successful outcome of MetD-AO has the potential to open up entirely new therapeutic opportunities in NAFLD.The complementary expertise of my host Dr. Stadler and me, a trained polymer chemist, will ensure a successful conduction of MetD-AO while it will enhance my future career prospects gaining experience in colloidal science and cell biology.

Оригинален текст от CORDIS (на английски).

Участници

AARHUS UNIVERSITET · Aarhus CКоординаторДания