Dark proteome as focus of a new Priority Program funded by the German Research Foundation

Professor Edward Lemke will be coordinating a new Priority Program researching the formation and function of characteristic protein complexes in the cell. The German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) has approved the establishment of the program from 2019, with a budget of EUR 6 million in the first three years. The Molecular Mechanisms of Functional Phase Separation program (SPP 2191) is in one of the most groundbreaking research areas in the life sciences supported by the German Research Foundation. In January 2019, Lemke was appointed Professor of Synthetic Biophysics at Johannes Gutenberg University Mainz (JGU) and, conjointly, an Adjunct Director at the Institute of Molecular Biology (IMB). He is also a fellow of Mainz University’s Gutenberg Research College. As a biophysical chemist, Lemke is a pioneer in the field of intrinsically disordered proteins.

“The DFG approval of the program is further proof of the excellence of life science research in Mainz and also represents another milestone in the successful collaboration between Mainz University and the Institute of Molecular Biology. As an Adjunct Professor, Lemke is able to link his research at the university particularly closely with his work at IMB. The dual affiliation opens up unique synergies in his discipline,” explained the Minister of Science of Rhineland-Palatinate, Professor Konrad Wolf. “Just a few days ago the nonprofit Boehringer Ingelheim Foundation and the state of Rhineland-Palatinate announced that they are granting IMB a further EUR 106 million from 2020 to 2027. The announcement of the new DFG program to be based at Mainz University validates this funding decision.”

Partially structured proteins for highly dynamic compartments

Proteins are the building blocks of life, present in every cell. They form muscle tissue and play essential roles as enzymes and in the immune response, to name just a few examples. The function of proteins was thought so far to be essentially dependent on their three-dimensional structure which is the result of the way in which the amino acid chains are folded. However, not all proteins have an ordered three-dimensional structure. A relatively large proportion, in humans estimated at over 30 percent, is formed by disordered or partially-ordered proteins. These intrinsically disordered proteins have, as a group, been termed the dark proteome. How these structures are employed by cells to enable novel dynamic functions was discovered only a few years ago.

“Our cells contain protein droplets, which swim in the cell fluid like oil drops on water,” Lemke described the current status of research. The protein droplets form via phase separation, in which the cell’s “spaghetti molecules,” i.e., the intrinsically disordered proteins and single-strand RNA, spontaneously bind together at high concentrations. “In the cells, new compartments form that are not separated from the rest of the cell by a membrane. These are small protein-RNA factories, which perform new functions and are highly dynamic,” explained Lemke. The nucleolus in the cell nucleus, in which many of the cell’s fundamental processes occur, is one such mini factory, while stress granules, which the cell forms in response to stress, are another example. However, when proteins incorrectly aggregate they can also result in a variety of diseases.

Understanding phase separation as a functional instrument of the cell

The new DFG Priority Program aims to shed light on these protein structures. The term “dark proteome” refers to the difficulty in visualizing the intrinsically disordered proteins in their original spaghetti-like state, making them difficult to study. “The focus of the Priority Program is to understand how cells exploit the phase separation. We are keen to find out the new functions that the collective of proteins perform. These are fundamental processes that, up to now, biology and the life sciences have largely overlooked,” asserted Lemke.

The scientists involved in SPP 2191 will be employing groundbreaking new experimental methods. Lemke also hopes that many concepts and techniques from polymer chemistry can be transferred into the life sciences. Thus, one potential source of collaboration is the Max Planck Institute for Polymer Research in Mainz.

The German Research Foundation has now invited proposals for the newly approved Priority Program to select individual project partners for the overarching subject area. DFG Priority Programs are usually funded for six years.

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