HITS researcher Dr. Kashif Sadiq explores ribonucleoprotein granules, a condensed form of bio-matter found inside cells. He investigates whether the rate of enzymatic reactions in these membrane-less granules is accelerated. If true, this would lead to new insights in how cells regulate their biochemistry and may shed light on the origins of life on Earth. The project is funded by the Volkswagen Stiftung with an “Experiment!” grant.
Cells are thought of as the basic unit of life. Each is a dynamic micro-world of billions of molecules involved in complex biochemical reactions. Cells control many of these internal reactions by physically separating the required molecules into membrane-bound compartments.
Proteins diffusing in and around an RNA granule inside the cell, against a backdrop of other RNA granules.
(Artistic impression, picture: Ina Poehner, Kashif Sadiq)
But, remarkably, when subjected to stress, such as extreme temperatures, mechanical damage and toxins, cells can also form membrane-less granules. These granules often contain self-assembled, condensed mixtures of proteins and long biopolymers like ribonucleic acids (RNAs) - together known as ribonucleoproteins (RNPs).
Excitingly, granules can co-exist in different phases of matter: liquid, gel, solid or even somewhere in between. And their function is still largely unknown. With theory and computer simulations, Dr. Kashif Sadiq from the Heidelberg Institute for Theoretical Studies (HITS) wants to explore the biophysical properties of these membrane-less granules. His independent research project called “RNA Epicatalysis” just started and is funded by the Volkswagen Stiftung with an “Experiment!” grant for 18 months.
Challenging the current paradigm of molecular biology
The main question Dr. Sadiq addresses in this project is whether the rate of enzymatic reactions in such granules might be accelerated. He aims to explore which factors affect and regulate their biomaterial properties and whether RNA is just a passenger or an active driver of this process. And if accelerated catalysis is possible, what is the basic physical mechanism that underpins it? Could specific macromolecular assemblies facilitate diffusion in these kinds of biomaterials? These questions have thus far remained inconclusive.
“Conventional enzymology would dismiss this counterintuitive idea because crowding by biopolymer meshes like RNP should slow down diffusion of enzymes and substrates”, Sadiq emphasizes. “But if true, that these granules can accelerate reactions, it would challenge the current paradigm of molecular biology yet again because it would imply a level of catalysis in cells above that of known enzymatic regulation.”
Shedding light on the origins of life
In doing so, Sadiq´s research aims to also shed light on some of the fundamental questions regarding the origins of life on Earth: Were the earliest self-replicating biomolecules billions of years ago able to self-organize into separated compartments – where biochemical reactions that aided their survival could be enhanced – only by using the physical laws of phase-separation, long before the first membraned-protocells had even evolved?
Dr. Kashif Sadiq read Natural Sciences at the University of Cambridge, UK, specializing in Theoretical Physics and writing his master’s thesis on the relativistic properties of fast plasma ejections around black holes. He earned his PhD in Computational Biophysics at University College London, UK and later worked in Postdoc positions in the UK and Spain - investigating the molecular dynamics, macromolecular assembly and catalytic reactions of biomolecules and biopolymers. Since 2016, Kashif Sadiq is a senior researcher in the Molecular and Cellular Modeling group (head: Prof. Rebecca Wade) at HITS.
The Volkswagen Foundation’s funding initiative 'Experiment!' tries to pave the way for fundamentally new research topics even though the outcome carries significant risk. Both a concept failure as well as unexpected findings are acceptable results. The funding initiative 'Experiment!' started in November 2012. It is both competitive and exceptionally well received with on average more than 500 applications per call. In the last call in 2017, 29 projects out of 594 proposals were selected.
Dr. Kashif Sadiq
Molecular and Cellular Modeling group (MCM)
Heidelberg Institute for Theoretical Studies (HITS)
Phone: +49 (0)6221 – 533 – 227
Dr. Peter Saueressig
Head of Communications
Heidelberg Institute for Theoretical Studies (HITS)
Phone: +49 6221 533 245
The Heidelberg Institute for Theoretical Studies (HITS) was established in 2010 by the physicist and SAP co-founder Klaus Tschira (1940-2015) and the Klaus Tschira Foundation as a private, non-profit research institute. HITS conducts basic research in the natural sciences, mathematics and computer science, with a focus on the processing, structuring, and analyzing of large amounts of complex data and the development of computational methods and software. The research fields range from molecular biology to astrophysics. The shareholders of HITS are the HITS Stiftung, which is a subsidiary of the Klaus Tschira Foundation, Heidelberg University and the Karlsruhe Institute of Technology (KIT). HITS also cooperates with other universities and research institutes and with industrial partners. The base funding of HITS is provided by the HITS Stiftung with funds received from the Klaus Tschira Foundation. The primary external funding agencies are the Federal Ministry of Education and Research (BMBF), the German Research Foundation (DFG), and the European Union.
https://www.h-its.org/scientific-news/kashif-sadiq-en/ HITS press release
https://www.volkswagenstiftung.de/en/funding/our-funding-portfolio-at-a-glance/e... "Experiment!" - VolkswagenStiftung
Dr. Peter Saueressig | idw - Informationsdienst Wissenschaft
Predicting a protein's behavior from its appearance
10.12.2019 | Ecole Polytechnique Fédérale de Lausanne
Could dark carbon be hiding the true scale of ocean 'dead zones'?
10.12.2019 | University of Plymouth
Graphene, a two-dimensional structure made of carbon, is a material with excellent mechanical, electronic and optical properties. However, it did not seem suitable for magnetic applications. Together with international partners, Empa researchers have now succeeded in synthesizing a unique nanographene predicted in the 1970s, which conclusively demonstrates that carbon in very specific forms has magnetic properties that could permit future spintronic applications. The results have just been published in the renowned journal Nature Nanotechnology.
Depending on the shape and orientation of their edges, graphene nanostructures (also known as nanographenes) can have very different properties – for example,...
Using a clever technique that causes unruly crystals of iron selenide to snap into alignment, Rice University physicists have drawn a detailed map that reveals...
University of Texas and MIT researchers create virtual UAVs that can predict vehicle health, enable autonomous decision-making
In the not too distant future, we can expect to see our skies filled with unmanned aerial vehicles (UAVs) delivering packages, maybe even people, from location...
With ultracold chemistry, researchers get a first look at exactly what happens during a chemical reaction
The coldest chemical reaction in the known universe took place in what appears to be a chaotic mess of lasers. The appearance deceives: Deep within that...
Abnormal scarring is a serious threat resulting in non-healing chronic wounds or fibrosis. Scars form when fibroblasts, a type of cell of connective tissue, reach wounded skin and deposit plugs of extracellular matrix. Until today, the question about the exact anatomical origin of these fibroblasts has not been answered. In order to find potential ways of influencing the scarring process, the team of Dr. Yuval Rinkevich, Group Leader for Regenerative Biology at the Institute of Lung Biology and Disease at Helmholtz Zentrum München, aimed to finally find an answer. As it was already known that all scars derive from a fibroblast lineage expressing the Engrailed-1 gene - a lineage not only present in skin, but also in fascia - the researchers intentionally tried to understand whether or not fascia might be the origin of fibroblasts.
Fibroblasts kit - ready to heal wounds
03.12.2019 | Event News
15.11.2019 | Event News
15.11.2019 | Event News
10.12.2019 | Architecture and Construction
10.12.2019 | Information Technology
10.12.2019 | Life Sciences