A German Research Foundation (DFG)-funded Emmy Noether Independent Junior Research Group at the Institute of Medical Physics and Biophysics will strengthen the research base at Charité – Universitätsmedizin Berlin. A team of early career researchers under the leadership of Dr. David Schwefel are studying the ‘ubiquitin system'. Ubiquitin is a protein involved in a wide range of cellular processes, and plays a crucial role in normal cell function. Approximately €1.5 million research funding have been awarded for a period of up to five years.
A variable lifespan is one of many distinguishing features of cellular proteins. Regulatory proteins, for instance, are switched off as soon as they have fulfilled their intended function. Faulty or damaged proteins also undergo degradation, so that their building blocks can be re-used. Ubiquitin represents an important component of the protein degradation pathway. A chain of ubiquitin molecules can be attached to other proteins, leading to modification of the protein's function or targeting it for degradation. Ubiquitination is involved in nearly all major cellular processes, including cell cycle regulation, DNA repair, and gene transcription.
Cullin-RING ubiquitin ligases represent the largest group of ubiquitination enzymes and are characterised by their modular nature. The modules which recognise and bind specific target proteins, the so-called substrate receptor modules, are exchangeable. In this way, a wide range of substrates can be accessed by the catalytic core of the ubiquitination enzyme.
“Attachment of ubiquitin protein chains to the target protein is highly specific, in order to prevent inaccurate regulation of protein concentration or activity,” says Dr. David Schwefel, who leads the new Emmy Noether research group. He goes on to explain that “over the next few years, we want to explore how the specificity of substrate recognition is determined on a molecular level, and how relatively similar receptor molecules are able to bind and ubiquitinate a variety of target proteins.” Additionally, the researchers want to study how immunodeficiency viruses, including the causative agent of AIDS, switch the ubiquitination pathway's substrate specificity, in order to improve conditions for virus replication in infected cells. “This will provide new insights into the mechanisms of virus infection, and might contribute to the development of new forms of treatment,” adds Dr. Schwefel.
Dr. David Schwefel
Institut für Medizinische Physik und Biophysik
Charité – Universitätsmedizin Berlin
t: +49 30 450 524102
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