Human genetic material contains more than 20,000 different genes. But each cell only uses a fraction of the information stored in this genome. Hence, cells have to control precisely which genes they use. If not, cancer or embryonal growth disorder may develop. So-called transcription factories play a central role in the selection of active genes. “These factories are molecular clusters in the nucleus that combine the correct selection of active genes and the read-out of their sequence at a central location,” Lennart Hilbert explains. The Junior Professor for Systems Biology/Bioinformatics at the Zoological Institute (ZOO) of KIT also heads a working group at KIT’s Institute of Biological and Chemical Systems — Biological Information Processing (IBCS-BIP).

Setup and Start within a Few Seconds

For decades, cellular and molecular biologists have studied how transcription factories are set up and taken into operation within a few seconds. Results obtained so far suggest relevance of processes known from industrial and technical polymer and liquid materials only. Current research focuses on phase separation as a central mechanism. In everyday life, phase separation can be observed when separating oil from water. It has not yet been clear, however, how exactly phase separation contributes to the setup of transcription factories in living cells.

Researchers from KIT’s Institute of Biological and Chemical Systems (IBCS), Zoological Institute (ZOO), Institute of Applied Physics (APH), and Institute of Nanotechnology (INT), in cooperation with scientists from FAU and MPZPM in Erlangen and the University of Illinois at Urbana-Champaign/USA, have now gained new findings on the formation of transcription factories: It is similar to the condensation of liquids. This is reported in Molecular Systems Biology. The first co-authors are Agnieszka Pancholi of IBCS-BIP and ZOO and Tim Klingberg of FAU and MPZPM.

Latest Light Microscopy Combined with Computer Simulations

In their publication, the researchers point out that condensation to form transcription factories resembles steamy glasses or windows. Liquid condenses in the presence of a receptive surface only, but then very quickly. In the living cell, specially marked areas of the genome are used as condensation surfaces. The liquid-coated areas allow for the adhesion of relevant gene sequences and additional molecules that eventually activate the adhering genes. These findings were obtained by interdisciplinary cooperation. Zebrafish embryos were studied with latest light microscopes developed by Professor Gerd Ulrich Nienhaus’s Chair at APH. These observations were then linked to computer simulations at the FAU Chair for Mathematics headed by Professor Vasily Zaburdaev. Combination of observations and simulations makes the condensation process reproducible and explains how living cells can set up transcription factories rapidly and reliably.

New understanding of condensed liquids in living cells recently resulted in entirely new approaches to treating cancer and diseases of the nervous system. These approaches are now being pursued by startups developing new drugs. Other research activities focus on the use of DNA sequences as digital data storage systems. Meanwhile, principle feasibility of DNA-based data storage systems has been demonstrated by several working groups. Reliable storage and read-out of information in such DNA storage media still represent big challenges. “Our work shows how the biological cell organizes such processes rapidly and reliably. The computer simulations and functional concepts developed by us can be transferred directly to artificial DNA systems and can support their design,” Lennart Hilbert says.

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Materials provided by Karlsruhe Institute of Technology. Note: Content may be edited for style and length.

“Heterotopic ossification is an incredibly debilitating condition for which we have no truly effective therapies,” said study leader Benjamin Levi, M.D., Associate Professor of Surgery and in the Children’s Medical Center Research Institute at UT Southwestern and the Charles and Jane Pak Center for Mineral Metabolism and Clinical Research. “To be able to prevent HO from occurring after an injury while also decreasing pain would be a substantial step forward.”

HO occurs in a significant number of patients with musculoskeletal injuries or who undergo some surgeries. For example, about 20% of patients undergoing an initial hip replacement develop this abnormal bone growth, and for a second replacement of the same hip, that number rises to up to 80%. HO is also common in patients with large-area burns, traumatic elbow injuries, spinal cord injuries, and pelvic fractures, where it causes contractures that limit mobility. Although pain during healing is an obvious feature of these injuries and surgeries, Dr. Levi explained, it’s been unclear whether pain-sensing nerves play a role in its development.

To investigate this question, Dr. Levi and Johns Hopkins colleague Aaron W. James, M.D., Ph.D., co-led a team of researchers from six institutions to determine how HO is affected by sensory nerves. Using a mouse model, the researchers observed that sciatic nerve axons — long extensions of neurons — grew into the injury site before HO occurred. When the nerve axons were not present, HO did not develop.

In an effort to identify the signal that draws sensory nerve axons into the injury site, the researchers surveyed gene activity to determine which genes might be over- or under-producing proteins after injury. They found that the amount of one protein, called nerve growth factor (NGF), increased several-fold after injury, and it came from cells on the outside of blood vessels. Because nerve fibers usually travel the same routes as blood vessels, NGF seemed like a likely beacon to draw axons in.

Sure enough, when the researchers used a genetic technique to shut down NGF- signaling at the injury site, HO did not develop. The researchers achieved similar success by using small molecules or an investigational drug to block TrkA, the receptor to which NGF binds.

Dr. Levi noted that several drugs that aim to relieve pain by blocking NGF are currently in phase 3 clinical trials at other institutions. These drugs could serve a dual purpose in patients at risk for HO by preventing this condition from developing.

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Materials provided by UT Southwestern Medical Center. Note: Content may be edited for style and length.

Dr. Fan Zhang, associate professor of physics in the School of Natural Sciences and Mathematics, is an author of a study published on Oct. 6 in the journal Nature that demonstrates the exotic behavior in bilayer graphene, which is a naturally occurring, two-atom thin layer of carbon atoms arranged in two honeycomb lattices stacked together.

The quantum Hall effect is a macroscopic phenomenon in which the transverse resistance in a material changes by quantized values in a stepwise fashion. It occurs in two-dimensional electron systems at low temperatures and under strong magnetic fields. In the absence of an external magnetic field, however, a 2D system may spontaneously generate its own magnetic field, for example, through an orbital ferromagnetism that is produced by interactions among electrons. This behavior is called the quantum anomalous Hall effect.

“When the rare quantum anomalous Hall effect was investigated previously, the materials studied were complex,” Zhang said. “By contrast, our material is comparably simple, since it just consists of two layers of graphene and occurs naturally.”

Dr. Thomas Weitz, an author of the study and a professor at the University of Göttingen, said: “Additionally, we found quite counterintuitively that even though carbon is not supposed to be magnetic or ferroelectric, we observed experimental signatures consistent with both.”

In research published in 2011, Zhang, a theoretical physicist, predicted that bilayer graphene would have five competing ground states, the most stable states of the material that occur at a temperature near absolute zero (minus 273.15 degrees Celsius or minus 459.67 degrees Fahrenheit). Such states are driven by the mutual interaction of electrons whose behavior is governed by quantum mechanics and quantum statistics.

“We predicted that there would be five families of states in bilayer graphene that compete with each other to be the ground state. Four have been observed in the past. This is the last one and the most challenging to observe,” Zhang said.

In experiments described in the Nature article, the researchers found eight different ground states in this fifth family that exhibit the quantum anomalous Hall effect, ferromagnetism and ferroelectricity simultaneously.

“We also showed that we could choose among this octet of ground states by applying small external electric and magnetic fields as well as controlling the sign of charge carriers,” Weitz said.

The ability to control the electronic properties of bilayer graphene to such a high degree might make it a potential candidate for future low-dissipation quantum information applications, although Zhang and Weitz said they are primarily interested in revealing the “beauty of fundamental physics.”

“We predicted, observed, elucidated and controlled a quantum anomalous Hall octet, where three striking quantum phenomena — ferromagnetism, ferroelectricity and zero-field quantum Hall effect — can coexist and even cooperate in bilayer graphene,” Zhang said. “Now we know we can unify ferromagnetism, ferroelectricity and the quantum anomalous Hall effect in this simple material, which is amazing and unprecedented.”

Other authors of the Nature article include UT Dallas physics doctoral student Tianyi Xu and researchers from the University of Göttingen and the Ludwig Maximilian University of Munich.

Zhang’s research is funded by the U.S. Army Combat Capabilities Development Command’s Army Research Laboratory and the National Science Foundation.

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Materials provided by University of Texas at Dallas. Original written by Amanda Siegfried. Note: Content may be edited for style and length.

New regulation as initial spark

Recently, because the first global regulation for Automated Lane Keeping Systems (ALKS) has been in force since the beginning of 2021. This law resolves the road approval dilemma, as Eichberger explains: “Until now, regulatory authorities did not know how to test and approve autonomous driving systems. The vehicle manufacturers, in turn, did not know what requirements the systems had to meet in order to be approved.” In the regulations, the approval criteria for highly automated systems (autonomous driving level 3) up to a maximum speed of 60 km/h have now been specified for the first time on the basis of a traffic jam assistant. When the assistant is activated, responsibility for control is transferred to the machine. The driver may take their hands off the steering wheel, but has to immediately take over again in the event of a malfunction. The system must recognize that the person behind the wheel is capable of doing this.

Based on this regulation, Eichberger and his research partners from Fraunhofer Austria, AVL and JOANNEUM RESEARCH have developed an efficient method over the last few months by which the readiness to take over control can be tested safely, efficiently, and to a high degree realistically in a driving simulator and the results can be used for the certification of ALKS systems.

Identical machine perception of the environment

Processes were required to prove the validity of the driving simulation using the test drive. The basis for this was a direct comparison — driving simulation and real driving (the AVL test track in Gratkorn, Styria, served as the test location) had to match as closely as possible. Here, the machine perception of the environment posed a challenge. Figuratively speaking, machine perception is the sensory organs of the vehicle. It has the task of precisely recording the vehicle’s surroundings — from the landscape and environmental objects to other road users — so that the driving assistance system can react appropriately to the situation. Eichberger: “If this is to run the same as in reality, the environments in the simulation have to match the real environment to the exact centimetre.”

Transferring the driving routes to the driving simulator

his accuracy is achieved using so-called “Ultra High Definition Maps” (UHDmaps®) from JOANNEUM RESEARCH (JR), one of the world’s leading research institutions in the field of digital twins. “We use a mobile mapping system to measure the test environments. Finally, a seamless 3D map with an extremely high level of detail is created from the measurement data. In addition to traffic infrastructure objects such as traffic signs, lane markings and guard rails, vegetation and buildings are also represented in this map,” says Patrick Luley, head of the research laboratory for highly automated driving at the DIGITAL Institute. While comparable accuracy can be achieved with manual 3D modelling, JR’s automated UHD mapping process is many times cheaper and faster.

The high-resolution 3D environment is finally transferred to the driving simulator. This is where the Fraunhofer Austria team come in. Volker Settgast from the Visual Computing business unit: “We prepare the data in such a way that the 3D environment can be displayed at high speed.” Even reflective and transparent surfaces or trees and bushes blown by the wind can be perceived naturally. Depending on the test scenario, additional vehicles or even people can then be added to the virtual environment.

The validation is finally verified with the help of comparative runs on the real route. “With our method, it is possible for car manufacturers to easily compare and validate a certain sampling on the real track and in the driving simulator. This means that the test can ultimately be transferred from the real track to the driving simulator,” says Eichberger. The TU Graz researcher and his team are now working on setting up virtual approval tests over the next few months.

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Materials provided by Graz University of Technology. Original written by Christoph Pelzl. Note: Content may be edited for style and length.