Scientists at Leipzig University, in collaboration with colleagues at Vilnius University in Lithuania, have developed a new method to measure the smallest twists and torques of molecules within milliseconds. The method makes it possible to track the gene recognition of CRISPR-Cas protein complexes, also known as “genetic scissors”, in real time and with the highest resolution. With the data obtained, the recognition process can be accurately characterised and modelled to improve the precision of the genetic scissors. The results obtained by the team led by Professor Ralf Seidel and Dominik Kauert from the Faculty of Physics and Earth Sciences have now been published in the prestigious journal Nature Structural and Molecular Biology.
When bacteria are attacked by a virus, they can defend themselves with a mechanism that fends off the genetic material introduced by the intruder. The key is CRISPR-Cas protein complexes. It is only in the last decade that their function for adaptive immunity in microorganisms has been discovered and elucidated. With the help of an embedded RNA, the CRISPR complexes recognize a short sequence in the attacker’s DNA. The mechanism of sequence recognition by RNA has since been used to selectively switch off and modify genes in any organism. This discovery revolutionized genetic engineering and was already honored in 2020 with the Nobel Prize in Chemistry awarded to Emmanuelle Charpentier and Jennifer A. Doudna.
Occasionally, however, CRISPR complexes also react to gene segments that differ slightly from the sequence specified by the RNA. This leads to undesirable side effects in medical applications. “The causes of this are not yet well understood, as the process could not be observed directly until now,” says Dominik Kauert, who worked on the project as a PhD student.
Scientists discovered that a synthetic cell with a reduced genome could evolve as quickly as a normal cell. Despite losing 45% of its original genes, the cell adapted and demonstrated resilience in a laboratory experiment lasting 300 days, effectively showcasing that evolution occurs even under perceived limitations.
“Listen, if there’s one thing the history of evolution has taught us is that life will not be contained. Life breaks free. It expands to new territories, and it crashes through barriers painfully, maybe even dangerously, but… ife finds a way,” said Ian Malcolm, Jeff Goldblum’s character in Jurassic.
The Jurassic period is a geologic time period and system that spanned 56 million years from the end of the Triassic Period about 201.3 million years ago to the beginning of the Cretaceous Period 145 million years ago. It constitutes the middle period of the Mesozoic Era and is divided into three epochs: Early, Middle, and Late. The name “Jurassic” was given to the period by geologists in the early 19th century based on the rock formations found in the Jura Mountains, which were formed during the Jurassic period.
Synthetic cells are a versatile technology with the potential to serve as smart delivery devices or as chassis for creating life from scratch. Despite the development of new tools and improvements in synthetic cell assembly methods, the biological parts used to regulate their activity have limited their reach to highly controlled laboratory environments12. In the field’s preliminary work, well-established arabinose and IPTG-inducible transcription factors and theophylline-responsive riboswitches were used to control in situ gene expression5,6. Still, each performed poorly in vitro and represented a leaky, insensitive route of transcription/translation control. Later, the transition to AHSL-sensitive transcription factors afforded synthetic cells the ability to sense and produce more biologically useful QS molecules, which are central to coordinating collective bacterial behaviors. Although this marked considerable progress toward integrating synthetic cells with living cells, the most frequently adopted QS systems used to date, LuxR/LuxI and EsaR/EsaI, recognize and synthesize the same AHSL (3OC6-HSL), limiting the variety of synthetic cell activators that work orthogonally5,7,10,11.
In this work, we diverged from using naturally derived parts to control gene expression, instead utilizing chemically modified LA-DNA templates to tightly and precisely control the location of synthetic cell activation with UV light. This LA-DNA approach was subsequently implemented to regulate communication with E. coli cells using the BjaI/BjaR QS system, adding this unique branched AHSL into the synthetic cell communication toolbox. We believe this system is ideally suited to synthetic cell communication. It couples an acyl-CoA-dependent synthase, BjaI, which efficiently synthesizes IV-HSL from its commercially available substrates, IV-CoA and SAM, with a highly sensitive IV-HSL-dependent transcription factor, BjaR, that activates gene expression at picomolar concentrations of IV-HSL.
Evolutionary biologist Jay T. Lennon’s research team has been studying a synthetically constructed minimal cell that has been stripped of all but its essential genes. The team found that the streamlined cell can evolve just as fast as a normal cell—demonstrating the capacity for organisms to adapt, even with an unnatural genome that would seemingly provide little flexibility.
Details about the study can be found in a paper featured in Nature. Roy Z. Moger-Reischer, a Ph.D. student in the Lennon lab at the time of the study, is first author on the paper.
“Listen, if there’s one thing the history of evolution has taught us is that life will not be contained. Life breaks free. It expands to new territories, and it crashes through barriers painfully, maybe even dangerously, but… ife finds a way,” said Ian Malcolm, Jeff Goldblum’s character in Jurassic Park, the 1993 science fiction film about a park with living dinosaurs.
Robotic finger. Illustration showing the cutting and healing process of the robotic finger (A), its anchoring structure (B) and fabrication process ©. ©2022 Takeuchi et al.
Researchers from the University of Tokyo pool knowledge of robotics and tissue culturing to create a controllable robotic finger covered with living skin tissue. The robotic digit has living cells and supporting organic material grown on top of it for ideal shaping and strength. As the skin is soft and can even heal itself, the finger could be useful in applications that require a gentle touch but also robustness. The team aims to add other kinds of cells into future iterations, giving devices the ability to sense as we do.
Professor Shoji Takeuchi is a pioneer in the field of biohybrid robots, the intersection of robotics and bioengineering. Together with researchers from around the University of Tokyo, he explores things such as artificial muscles, synthetic odor receptors, lab-grown meat, and more. His most recent creation is both inspired by and aims to aid medical research on skin damage such as deep wounds and burns, as well as help advance manufacturing.
Artificial intelligence can predict on-and off-target activity of CRISPR tools that target RNA instead of DNA, according to new research published in Nature Biotechnology.
The study by researchers at New York University, Columbia University, and the New York Genome Center, combines a deep learning model with CRISPR screens to control the expression of human genes in different ways—such as flicking a light switch to shut them off completely or by using a dimmer knob to partially turn down their activity. These precise gene controls could be used to develop new CRISPR-based therapies.
CRISPR is a gene editing technology with many uses in biomedicine and beyond, from treating sickle cell anemia to engineering tastier mustard greens. It often works by targeting DNA using an enzyme called Cas9. In recent years, scientists discovered another type of CRISPR that instead targets RNA using an enzyme called Cas13.
Is the Executive Director of the Innovative Genomics Institute (https://innovativegenomics.org/people/brad-ringeisen/), an organization founded by Nobel Prize winner Dr. Jennifer Doudna, on the University of California, Berkeley campus, whose mission is to bridge revolutionary gene editing tool development to affordable and accessible solutions in human health and climate.
Dr. Ringeisen is a physical chemist with a Ph.D. from the University of Wisconsin-Madison, a Bachelor of Science in chemistry from Wake Forest University, a pioneer in the field of live cell printing, and an experienced administrator of scientific research and product development.
Before joining the IGI, Dr. Ringeisen was Director of the Biological Technologies Office at DARPA, where he managed a division working at the cutting edges of biology, physical sciences and engineering. Programs in his office included research in genome editing, epigenetics, neurotechnology, food security and biomanufacturing, as well as diagnostics and therapeutics development.
Prior to DARPA, Dr. Ringeisen ran his own research group at the U.S. Naval Research Laboratory as the head of the Bioenergy and Biofabrication Section where he oversaw diverse research programs including the development and application of laser-assisted printing approaches to biology, development of organs-on-a-chip, microbial energy harvesting and extracellular electron transfer as well as microbial discovery and microbiome characterization.
Dr. Ringeisen now uses his amazing expertise to guide IGI’s scientific and development strategy, but his duties also include promoting entrepreneurship, working with biotech investors and companies to ensure commercial translation of technologies, donor outreach and development, scientific project development and team building, communication with campus leadership, personnel management and mentoring, program management, and reporting and engagement with both Governance and Scientific Advisory Boards.
Developing The Low Earth Orbit Economy On The World’s First Commercial Space Station — David Zuniga, Senior Director, In-Space Solutions, Axiom Space
David Zuniga is Senior Director of In-Space Solutions at Axiom Space (https://www.axiomspace.com/), a space infrastructure developer headquartered in Houston, Texas, which plans human spaceflight for government-funded and commercial astronauts, engaging in in-space research, in-space manufacturing, and space exploration. The company aims to own and operate the world’s first commercial space station, and Mr. Zuniga helps to develop strategy and growth around Axiom’s Low Earth Orbit (LEO) economy, also playing a critical role in business and technical integration of Axiom’s in-space manufacturing and research capabilities for Axiom Station architecture.
Mr. Zuniga has over 20 years of experience through engineering and business development in human spaceflight and the department of defense, developing system architectures and technology for deep space systems via the Constellation, Orion, and Gateway programs. He was a Certified Principal Engineer for Orion’s Air Revitalization System, and subsystem manager for NASA’s Gateway program for the Environmental Control and Life Support Systems (ECLSS) where he developed requirements and certification criteria for future architectures.
Mr. Zuniga also has helped to evolve strategy around growth for LEO commercialization through the Center for the Advancement of Science in Space (CASIS) where he created a pipeline and managed a portfolio for aerospace technology development projects on the International Space Station National Laboratory (ISS NL). He has also served in numerous committees around human spaceflight safety and commercialization, has been an invited speaker to brief NASA HQ on strategy for the ISS NL, and was the recipient of the top prize at NASA’s Ignite the Night competition through NASA iTech when serving as the managing director for the Danish Aerospace Company’s North American Division.
Mr. Zuniga earned Bachelor and Master of Science degrees in Mechanical Engineering from Texas A&M University and holds a graduate certification in Space Resources from Colorado School of Mines where he studied space policy, economics, and space resource utilization.