The transport routes of nutrients and messenger cargos can be compared to the traffic system of a city: A worldwide unique quantitative study of cell biologists of the University of Zurich shows that cells regulate the main routes, side routes and intersections by an intricate traffic control system, which guides the spatial and temporal distribution of substances within the cell.
Cells must transport nutrients and messenger cargos through its membrane and transport them within the cell at the correct time and place. This procedure is complex and is regulated with the help of specific genes. If disturbances in the transport mechanism arise, severe diseases, such as diabetes, cancer and diverse neurological pathologies, are the consequence.
The discovery of the molecular principles of cellular transport was honored with the Nobel Prize of physiology and medicine in 2013. While knowing the intracellular roads and the functioning of the cars that use these roads is essential knowledge, one cannot understand much of how a cell functions without knowing how all this traffic is regulated and controlled.
Cell and systems biologists of the University of Zurich could now create a first global map of the regulatory control systems of the majority of transport routes in a cell. This unique map has been published by the renowned scientific journal Cell as its cover story.
How cells uptake and transport cargos
Cells regulate the uptake of nutrients and messenger cargos and their transport within the cell. This process is known as endocytosis and membrane traffic. Different cargos dock onto substrate specific receptors on the cell membrane. Special proteins such as kinases, GTPases and coats, activate specific entry routes and trigger the uptake of the receptors into the cell. For their uptake, the receptors and docked cargos become enclosed by the cell membrane. In the next steps, the membrane invaginates and becomes constricted. The resulting vesicle is guided via several distinct stations, cellular organelles, to its final destination in the cell.
Cells regulate the main routes, side routes and intersections
For her study, Dr. Prisca Liberali, senior scientist in the team of Professor Lucas Pelkmans, sequentially switched off 1200 human genes. Using automated high-throughput light microscopy and computer vision, she could monitor and compare 13 distinct transport paths involving distinct receptors and cellular organelles. Precise quantifications of thousands of single cells identified the genes required for the different transport routes. Surprisingly, sets of transport routes are co-regulated and coordinated in specific ways by different programs of regulatory control.
Subsequently, Dr. Liberali calculated the hierarchical order within the genetic network and thereby identified the regulatory topology of cellular transport. “The transport into the cell and within the cells proceeds analogously to the cargo transport within a city” describes the scientist. “Like in a city, the traffic on the routes within a cell and their intersections is tightly regulated by traffic lights and signs to guide the cargo flow.”
Thanks to this unique quantitative map, the fine regulatory details of transport paths and processes within a cells could be mapped for the first time. Particularly the genes that encode for these traffic lights and switches are often de-regulated in disease. With this map, it is now possible to predict how this leads to traffic jams in the cells, causing the disease phenotype. Alternatively, since many drugs have been developed to target these traffic lights and switches, the map can be used to come up with possible drug combinations to target unwanted traffic, such as viruses, to the waste disposal system of the cell.
Prisca Liberali, Berend Snijder, Lucas Pelkmans. A hierarchical map of regulatory genetic interactions in membrane trafficking. Cell. June 5, 2014. DOI: http://dx.doi.org/10.1016/j.cell.2014.04.029
Dr. Prisca Liberali
Institut für Molekulare Biologie
Tel. +41 44 635 31 94 / +41 77 459 57 53
Tel. +41 44 634 44 39
Bettina Jakob | Universität Zürich
An evolutionary heads-up – The brain size advantage
22.05.2015 | Veterinärmedizinische Universität Wien
Endocrine disrupting chemicals in baby teethers
21.05.2015 | Goethe-Universität Frankfurt am Main
Physicists have developed an innovative method that could enable the efficient use of nanocomponents in electronic circuits. To achieve this, they have developed a layout in which a nanocomponent is connected to two electrical conductors, which uncouple the electrical signal in a highly efficient manner. The scientists at the Department of Physics and the Swiss Nanoscience Institute at the University of Basel have published their results in the scientific journal “Nature Communications” together with their colleagues from ETH Zurich.
Electronic components are becoming smaller and smaller. Components measuring just a few nanometers – the size of around ten atoms – are already being produced...
Development and implementation of an advanced automobile parking navigation platform for parking services
To fulfill the requirements of the industry, PolyU researchers developed the Advanced Automobile Parking Navigation Platform, which includes smart devices,...
The world's first electrical car and passenger ferry powered by batteries has entered service in Norway. The ferry only uses 150 kWh per route, which...
On Tuesday, 19 May 2015 the research icebreaker Polarstern will leave its home port in Bremerhaven, setting a course for the Arctic. Led by Dr Ilka Peeken from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) a team of 53 researchers from 11 countries will investigate the effects of climate change in the Arctic, from the surface ice floes down to the seafloor.
RV Polarstern will enter the sea-ice zone north of Spitsbergen. Covering two shallow regions on their way to deeper waters, the scientists on board will focus...
Nanoengineers at the University of California, San Diego developed a gel filled with toxin-absorbing nanosponges that could lead to an effective treatment for skin and wound infections caused by MRSA (methicillin-resistant Staphylococcus aureus), an antibiotic-resistant bacteria. This "nanosponge-hydrogel" minimized the growth of skin lesions on mice infected with MRSA - without the use of antibiotics. The researchers recently published their findings online in Advanced Materials.
To make the nanosponge-hydrogel, the team mixed nanosponges, which are nanoparticles that absorb dangerous toxins produced by MRSA, E. coli and other...
20.05.2015 | Event News
18.05.2015 | Event News
12.05.2015 | Event News
22.05.2015 | Materials Sciences
22.05.2015 | Information Technology
22.05.2015 | Materials Sciences