07-Jun-2021 - Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH

The Cut and Restore Protein Trick: Self-Excising Designer Proteins Report Isoform Expression

Our proteome is much bigger than our genome because one gene produces several variants of proteins called protein isoforms, whose disbalance is implicated in many diseases. A new bioengineered reporter system developed at Helmholtz Zentrum München and the Technical University of Munich now allows for the first time to follow protein isoform expression over time in live cells. The method helps to decipher the underlying regulatory mechanisms and enables screening for potential molecular interventions.

Proteins are the key players in our cellular processes. Their generation follows principles called transcription and translation. First, DNA copies its genetic information to messenger RNA (mRNA), which then determines the sequence in a chain of amino acids, which finally fold into a protein. The reality, however, is more complex: More than 90 per cent of our genes do not result in only one mRNA and then one protein, but a process called alternative splicing produces several mRNA variants, only some of which are then translated into a specific protein isoform in a specific cell at a given time. Conventional techniques to detect alternative splicing are mostly single time-point measurements that are work-intense and cannot reliably monitor over time which protein isoforms are actually translated in the cell.

Researchers at Helmholtz Zentrum München and the Technical University of Munich (TUM) thus developed a new bioengineered reporter system called EXSISERS. The idea behind it is to generate a signal such as light as soon as a specific protein isoform is being translated. “This is possible via designer reporter proteins that can cut themselves out of the nascent amino acid chain– they are self-excising,” says Dong-Jiunn Jeffery Truong. “In analogy to the famous cut and restore rope trick in magic performances, the excision of the reporter leaves no scar in the natural protein isoforms.” The researchers have already applied this method to human cells in culture. One of their aims was to analyze the expression of isoforms of a protein called Tau, which is associated with neurodegenerative diseases such as Parkinson’s. This makes Tau isoforms a potential target for future molecular therapies.

“Bioengineering inspired by natural biomolecular processes will make it possible to observe many other fundamental cellular processes non-invasively,” says Gil Gregor Westmeyer. “The more cellular parameters we can monitor, the better we can develop targeted molecular interventions for future cellular therapies, for example, to treat neurodegenerative diseases.” Westmeyer and his team are already collaborating with several academic laboratories that use the new reporter system to obtain a more comprehensive understanding of isoform expression in cells and its implication in diseases.

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH

Recommend news PDF version / Print Add news to watchlist

Share on

Facts, background information, dossiers

  • isoforms
  • proteins
  • Expression

More about Helmholtz Zentrum München

  • News

    Pancreatic organoids on newly developed chip platform

    A new organoid-on-chip platform robustly mimics the key features of human pancreas development. This is a milestone on the way to being able to diagnose pancreatic cancer at an early stage in the future. The study was conducted by an interdisciplinary team of researchers from Helmholtz Zent ... more

    Revealing the secrets of cell competition

    Cellular competition is a crucial quality control process that ensures that the development of an organism relies on healthy cells. Researchers revealed the secrets underlying cell competition and what features can pre-determine whether a cell will survive or not. Defects in energy producti ... more

    Sars-Cov-2 infects cells via specific viral entry factors that are more abundant in elderly, men and smokers

    A new study uncovers which cell types can be infected by SARS-CoV-2 due to their viral entry factors. The study also suggests that increased gene expression of these viral entry factors in some individuals partially explains the differences of COVID-19 severity reported in relation to age, ... more

  • q&more articles

    Using deep learning to better understand blood disorders

    For a long time, doctors have been diagnosing disorders of the body’s hematopoietic system using a light microscope. The analysis of individual blood cells is largely performed manually. Now, artificial intelligence can lend them a digital hand. more

  • Authors

    Dr. Carsten Marr

    Carsten Marr, born in 1977, received his diploma in general physics from the Technische Universität München in 2002. He wrote his diploma thesis at the Max-Planck-Institute for Quantum Optics, Garching, Germany, and in 2003 visited the Quantum Information and Quantum Optics Theory Group at ... more

    Dr. Christian Matek

    Christian Matek, born in 1986, received undergraduate degrees in both Physics and Medicine in Munich. He then moved to the UK and finished his DPhil in Theoretical Physics at Oxford University in 2014. Since 2017, his main research interest has been applying artificial intelligence and mach ... more

More about TU München

  • News

    New approach identifies T cells in Covid-19 patients

    T cells play a decisive role in fighting the coronavirus and preventing infected individuals from becoming seriously ill. They identify and fight the virus directly within the infected cells. A team of researchers working in Munich have produced a precise profile of the T cells that respond ... more

    The virus trap

    To date, there are no effective antidotes against most virus infections. An interdisciplinary research team at the Technical University of Munich (TUM) has now developed a new approach: they engulf and neutralize viruses with nano-capsules tailored from genetic material using the DNA origam ... more

    Versatile and reliable SARS-CoV-2 antibody assay

    During the continued progression of the Corona pandemic, rapid, inexpensive, and reliable tests will become increasingly important to determine whether people have the associated antibodies – either through infection or vaccination. Researchers at the Technical University of Munich (TUM) ha ... more

  • q&more articles

    Biobased raw material flows of the future

    Anthropogenic climate change and the rising world population, in combination with increasing urbanization, poses global challenges to our societies that can only be solved by technological advancement. The direct biotechnological use of greenhouse gases, including residual biomass flows fro ... more

    Taste and aroma boost in the mouth

    The food trend towards healthy snacks is continuing. Snacks made from freeze-dried fruit meet consumer expectations of modern and high-quality food. However, freeze drying of whole fruits requires long drying times and substantially reduces sensorial quality, which is unappealing to consumers. more

    Diet, gut microbiota and host lipid metabolism

    Nature provides an enormous diversity of lipid molecules that originate from various pathways. Fatty acids are key modules for various lipids, including cell membrane lipids such as phospholipids or triacylglycerols, which are the major components of lipid droplets. Excess lipids or defects ... more

  • Authors

    Prof. Dr. Thomas Brück

    Thomas Brück, born in 1972, obtained his B.Sc. in chemistry, biochemistry and management science from Keele University, Stoke on Trent. Additionally, he holds an M.Sc. in molecular medicine from the same institution. In 2002, Thomas obtained his Ph.D. in Protein Biochemistry from Imperial C ... more

    Dr. Norbert Mehlmer

    Norbert Mehlmer, born in 1977, studied biology at the University of Salzburg and wrote his diploma thesis at the Max Planck Institute for Molecular Genetics in Berlin. He earned his doctorate in genetics/microbiology at the Max F. Perutz Laboratories (MFPL) of the University of Vienna. Subs ... more

    Dr. Mahmoud Masri

    Mahmoud Masri accomplished his studies in Applied Chemistry at the University of Damascus and received his Master in 2010. He has been working as Quality Assurance Manager for five years. In 2019, he obtained his doctoral degree in biotechnology at the Technical University of Munich (TUM) w ... more

q&more – the networking platform for quality excellence in lab and process

The q&more concept is to increase the visibility of recent research and innovative solutions, and support the exchange of knowledge. In the broad spectrum of subjects covered, the focus is on achieving maximum quality in highly innovative sectors. As a modern knowledge platform, q&more offers market participants one-of-a-kind networking opportunities. Cutting-edge research is presented by authors of international repute. Attractively presented in a high-quality context, and published in German and English, the original articles introduce new concepts and highlight unconventional solution strategies.

> more about q&more

q&more is supported by: