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Matthias Hinterndorfer receives Denise P. Barlow Award

09 May 2023
Matthias Hinterndorfer (credit: IMP)

Matthias Hinterndorfer, an IMP alumnus from the lab of Johannes Zuber, received the 2022 Denise P. Barlow Award for his outstanding doctoral thesis. During his time at the IMP, he developed a new screening approach to studying gene function and networks in mammalian cells. On top of that, Matthias uncovered the structure and role of AKIRIN2, a protein that facilitates the import of the proteasome into the cell nucleus. He is now a postdoctoral researcher at the Research Center for Molecular Medicine (CeMM).

The discovery of CRISPR/Cas9 has transformed our ability to investigate the function of genes and genetic networks in mammalian cells. One particularly impressive application is the use of pooled CRISPR screens, in which large sets of genes can be disrupted one by one, to observe their effects on a particular cellular process. During his PhD with Johannes Zuber, Matthias Hinterndorfer engineered a pipeline for high-quality, genome-wide CRISPR/Cas9 screening that enables the identification of essential genes and their regulators.

When inferring the function of genes in CRISPR screens, the experimenter often relies on the cells’ growth and survival. As a result, the functions of highly essential genes are difficult to study: as soon as the genes are deleted, cells are rushed to their death.

To overcome this issue, Matthias brought CRISPR screen technologies to a new level. Together with Melanie de Almeida, another PhD student in the Vienna BioCenter PhD Program, he developed a time-controlled screening assay in which Cas9, the “DNA scissors” that knock genes out, can be expressed on-demand. This allows them to study the immediate consequences of gene knockouts before the cells start dying.

Matthias and Melanie used this approach to study the regulation of MYC, an essential protein for the growth of cancer cells. They identified numerous regulators of MYC, including the novel factor AKIRIN2. They found that this small, essential protein plays a fundamental role in keeping the cell nucleus clean: it helps the proteasome – the cell’s clean-up machinery – enter the nucleus to break down unwanted proteins in this compartment. Without AKIRIN2, the nucleus is left with an ever-expanding accumulation of proteins, such as MYC, which eventually leads to the cell’s demise.For this ground-breaking discovery published in Nature and his technology development, Matthias received the Denise P. Barlow Award yesterday, in a ceremony held in the Festival Hall of the Austrian Academy of Sciences.

Left to right: Johannes Zuber, Matthias Hinterndorfer, Giulio Superti-Furga (credit: Franzi Kreis/CeMM)

“I am deeply honoured that the award selection committee shares our excitement about our approach and fundamental discovery,” Matthias says. “I can’t emphasise enough the role that Melanie de Almeida and our collaborators played in this project. It was a true team effort, and this award also highlights the power of teamwork and collaborative research.”

Matthias is the second PhD student from the lab of Johannes Zuber to win the award since its first edition in 2018.

About the Denise P. Barlow Award

Denise Barlow had a prolific scientific career, mostly remembered for her contributions to early epigenetics. A detailed account of the work she had done while starting her lab at the IMP can be found on this website. Denise’s career, however, continued to span four institutions in Vienna: following the IMP, where she was a group leader, it also included the Max Perutz Labs, where she was a professor, IMBA, which provided laboratory space for some time, and CeMM, where she was a principal investigator until her retirement.

Following Barlow’s untimely passing in 2017, these four institutions launch an annual award in her name to merit exceptionally interesting PhD studies carried out in one of the four institutions. Specifically, the Denise P. Barlow Award intends to promote the academic career of young scientists, strategically addressing the transition of graduated PhD students to postdocs, by offering a small financial help that will alleviate the costs associated with relocation or career development. 

The “Denise P. Barlow Award” amounts to 5,000 Euro. After two years of postdoc research, awardees are invited to give a talk, and while in Vienna, participate to the award of the next winner. The topic of the thesis can vary and cover basic cell biological, biochemical, molecular biological, structural and computational work, with an emphasis on insight on new biological mechanisms, something Denise P. Barlow was fond of. The award selection committee comprises seven people, including the four scientific directors of the awarding institutes. Due to the current pandemic, the 2019 award was announced with a delay.

Further reading

Vienna BioCenter PhD Program

Research with Johannes Zuber

How cells keep their nucleus clean: a fundamental discovery