Cosmas Arnold and Matthias Muhar receive OeGMBT Life Science Research Award
The OeGMBT Life Science Research Award Austria is endowed annually by the Austrian Association of Molecular Life Sciences and Biotechnology (OeGMBT) to honor young researchers who have published a scientific paper of exceptional quality. This year, the awards in the two categories—Basic Science and Applied Research—go to IMP-scientists: Cosmas Arnold (shown in the image on the right), a senior postdoc and research associate in the lab of Alex Stark, and Matthias Muhar (left), a PhD-student in the lab of Johannes Zuber.
Cosmas Arnold receives the award in the Basic Science category for his paper ‘Genome-wide assessment of sequence-intrinsic enhancer responsiveness at single-basepair resolution’, published in Nature Biotechnology in February 2017. At the core of the paper is a method called STAP-seq, short for ‘self-transcribing active core promoter sequencing’, which was conceived, developed and optimized by Cosmas. It allows researchers to study promoters, gene sequences that activate transcription and are in turn controlled by enhancers.
Prior to this development, scientists had no means to systematically assess the regulatory functions of promoters and it was assumed that they were mostly passive platforms for the initiation of transcription. Applying STAP-seq to the Drosophila genome, Cosmas, together with Mamduh Zabidi, a bioinformatics PhD student in the Stark lab, found that the enhancer responsiveness and transcription levels of promoters differ by several orders of magnitude. STAP-seq therefore has enormous potential, not only for research on promoters and their regulatory function in transcriptional regulation but also for biotechnological applications such as protein production.
Cosmas Arnold received his diploma in Biology from the University of Regensburg. In 2009, he joined the lab of Alex Stark at the IMP through the Vienna BioCenter PhD-Programme. During his PhD, he developed STARR-seq, a powerful assay to quantitatively measure genome-wide enhancer activity. In 2013, he obtained his PhD and currently is a Senior Postdoctoral Researcher and Research Associate at the IMP.
Matthias Muhar receives the award in the Applied Research category for his paper ‘SLAM-seq defines direct gene-regulatory functions of the BRD4-MYC axis” which was published in Science in May 2018. The paper addresses a problem that is key to understanding the roles of transcription factors and regulatory pathways in physiology and diseases, such as cancer. To elucidate their functions, it is crucial to know which genes they control. Established methods do not allow for drawing conclusions about direct regulatory relationships.
In his PhD project, Matthias Muhar addressed this fundamental challenge by combining CRISPR genome engineering, targeted protein degradation, and SLAM-seq, a method that was recently developed by the group of Stefan Ameres at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA). Matthias thereby was able to define the regulatory functions of two important transcriptional hubs in cancer, BRD4 and MYC, which had long evaded a definitive experimental characterization. The study not only identifies direct targets of BRD4 and MYC but also elucidates the underlying mechanism of an emerging therapeutic concept: treatment with BET bromodomain inhibitors (BETis).
On a more general scope, the study establishes a simple and scalable strategy to identify direct transcriptional targets of any gene or pathway. Owing to its broad application potential, the method could soon become a standard technique in basic and applied biomedical research. “I am particularly grateful to receive this award in applied sciences for a project that started with a very basic biological question”, says Matthias. “This just perfectly illustrates how fundamental research can spur the development of technologies that are also applicable outside of academia.”
Matthias Muhar studied Biology at the University of Vienna. After obtaining his Master’s degree in 2014, he joined the lab of Johannes Zuber at the IMP through the Vienna BioCenter PhD-Programme. In his PhD project, Matthias focusses on the systematic characterisation of transcriptional regulation in leukemic self-renewal.
The OeGMBT Life Science Research Awards Austria come with a prize money of 3000 Euros each. The two awards, together with a special award in ‘Excellence & Societal Impact’, will be handed over on 17 September during the OeGMBT Annual Meeting ‘Ten years life, science and molecules’ in Vienna.
Arnold CD, Zabidi MA (co-first authors), Pagani M, Rath M, Schernhuber K, Kazmar T, Stark A: Genome-wide assessment of sequence-intrinsic enhancer responsiveness at single-base-pair resolution. Nat Biotechnol. 2017 Feb;35(2):136-144. doi: 10.1038/nbt.3739.
Muhar M, Ebert A, Neumann T, Umkehrer C, Jude J, Wieshofer C, Rescheneder P, Lipp JJ, Herzog VA, Reichholf B, Cisneros DA, Hoffmann T, Schlapansky MF, Bhat P, von Haeseler A, Köcher T, Obenauf AC, Popow J, Ameres SL, Zuber J: SLAM-seq defines direct gene-regulatory functions of the BRD4-MYC axis. Science. 2018 May 18;360(6390):800-805. doi: 10.1126/science.aao2793.
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