17 April 2015
YI Sebastian Marquardt receives a Hallas-Møller fellowship from the Novo Nordisk Foundation
The grant is awarded to establish his own research group at the Copenhagen Plant Science Centre and his project is supported with DKK 11 million for the next five years.
Sebastian Marquardt’s project is about “Functional dissection of long non-coding RNA (lncRNA) transcription”. Description of the project: Complex organisms often have large genomes but most DNA does not code for proteins (non-coding DNA). RNA polymerase II (Pol II) transcribes non-coding DNA into long non-coding RNA (lncRNA) on a genome-wide scale. Despite abundant lncRNA transcription it is not clear how this is functionally important.
My proposal focuses on characteristics of lncRNA transcription common to a wide range of organisms to elucidate the core concepts. Transcription in the opposite direction to genes from promoters represents a conserved source of lncRNA (divergent lncRNA). This common origin enables us to discover over-arching principles underlying their production. I will identify regulators of divergent lncRNA transcription as mutants in genetic screens that over-express or reduce divergent lncRNA production. The scale of divergent lncRNA mis-regulation will be revealed by implementing cutting-edge nascent transcriptomics methods. Discovering the rules underlying divergent lncRNA biogenesis will enable us to perform crucial loss-of-function approaches to address the functional significance of non-coding transcription across organisms.
An important common characteristic of lncRNA is their transcriptional plasticity, in response to changing environments or across different cell types. I aim to dissect if and how these rapid changes of the transcription landscape confer advantages when coping with environmental fluctuations. My focus will be on investigating how the act of non-coding transcription can itself be a function by interfering with nearby gene expression. As lncRNA show little sequence conservation, this research addresses how non-coding regions could function beyond the produced lncRNA molecule. I identified suitable models to isolate indicative molecular hallmarks of this phenomenon and will determine its scope in higher organisms. My functional dissection of non-coding sequences promises to discover novel paradigms of organizing genomic information.