H2020Индивидуална стипендия2015–2017

Evolutionary Neurogenomics · The impact of recent retrotransposon invasions on the evolution of human neural gene expression

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

Период: 2015-06-01 → 2017-05-31
Финансиране от ЕС: 177 599 €
Участници: 1
Схема: MSCA-IF-EF-RI

Линиите свързват координатора с партньорите.

Накратко на български

Ретротранспозоните (подвижни генетични елементи) се изследват за това как контролират експресията на гени в човешкия мозък. Това помага да се разбере еволюцията на мозъка и защо хората са податливи на определени неврологични 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

The impact of recent retrotransposon invasions on the evolution of human neural gene expression

In this research program, I made the first steps to determine how recent retrotransposon insertions have shaped gene-regulatory pathways involved in human brain development. Through a combination of bioinformatics and human and non-human primate stem cell cortical neuron differentiation protocols, I aimed to identify neuronally expressed genes that have become under the control of retrotransposons. Knowing exactly how each class of retrotransposons have impacted human gene expression will allow us to explore these novel gene-regulatory properties may have come indispensable for the human brain and possibly contain clues to the increased susceptibility of humans to some neurological disorders. The long term goal of my research program is to investigate how waves of retrotransposon insertions have contributed to the evolution of human gene expression patterns and how these changes relate to human-specific aspects of brain development in health and disease.

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

Цел на проекта

Throughout evolution, primate genomes have been under attack by different classes of retrotransposons, retrovirus-derived mobile DNA elements. As a result, an astonishing ~50% of the human genome is derived from many types of retrotransposons. I previously showed that primate-specific retrotransposon invasions are restricted by primate-specific KRAB zinc finger proteins. These findings suggest that through recruitment to thousands of new genomic locations, KRAB zinc finger proteins have become intimately integrated into pre-existing gene regulatory pathways. Retrotransposons are an important source for evolutionary novelties, but the impact of thousands of human-specific retrotransposon-KZNF regulatory modules on the evolution of human gene expression patterns is unknown. There is increasing evidence that retrotransposons become reactivated during neural differentiation, suggesting that neuronal gene-regulatory networks may be extra sensitive to retrotransposon insertions. Furthermore, new retrotransposon insertions may hold clues to the mechanism of human disease: Even when retrotransposons are efficiently silenced in health, they may become aberrantly activated by changes in DNA methylation observed in neurological diseases and cancer. Using a previously established human and non-human primate stem cell cortical neuron differentiation assay, I will identify, validate and functionally test neurodevelopmental genes that have come under the control of retrotransposons. This will address the impact of recent waves of retrotransposon insertions on the evolution of human neural gene expression patterns and opens up the exploration of how new retrotransposon insertions may be correlated to human neurological disorders. The Marie Skłodowska-Curie individual fellowship will provide the opportunity to establish my research group in Europe and re-integrate in Dutch and EU networks, as well as allow me to achieve my professional development training goals.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITEIT VAN AMSTERDAM · AmsterdamКоординаторНидерландия