Recording analog memories in human cells

MIT biological engineers have devised a way to record complex histories in the DNA of human cells, allowing them to retrieve “memories” of past events, such as inflammation, by sequencing the DNA.



This analog memory storage system — the first that can record the duration and/or intensity of events in human cells — could also help scientists study how cells differentiate into various tissues during embryonic development, how cells experience environmental conditions, and how they undergo genetic changes that lead to disease.

Self-assembling protein icosahedral shell designed

The same 20-sided solid that was morphed into geodesic domes in the past century may be the shape of things to come in synthetic biology.

For University of Washington Institute of Protein Design scientists working to invent molecular tools, vehicles, and devices for medicine and other fields, the icosahedron’s geometry is inspiring. Its bird cage-like symmetry and spacious interior suggest cargo-containing possibilities.



The protein designers took their cue from the many viruses that, en route to living cells, transport their genomes inside protective icosahedral protein shells. These delivery packages, termed viral capsids, are formed to be tough enough to withstand the trip, efficiently use storage room, and break apart to release their contents when conditions are right.

The researchers’ paper in the scientific journal Nature reports on their computational design and experimental testing of a highly stable icosahedral protein nano-cage. Engineered at the atomic level, this nano-cage can construct itself from biochemical building blocks and information encoded in strands of DNA.

After selecting the design for this icosahedral nano-cage through computer modeling, the researchers produced it in bacteria. Electron microscopy of the resulting icosahedral particles confirmed that they were nearly identical to the design model.



The leads on the project were Yang Hsia, a University of Washington graduate student in biological physics, structure and design, and Jacob B. Bale, a recent graduate from the UW molecular and cellular biology Ph.D. program, and now a research scientist at Arzeda Corporation in Seattle. The senior authors were Neil P. King, translational investigator at the UW Institute for Protein Design, and David Baker, director of the Institute and UW professor of biochemistry. Baker is also an investigator with the Howard Hughes Medical Institute.

“The ability to design proteins that self-assemble into precisely specified, robust, and highly order icosahedral structures,” the researchers wrote, “would open the door to a new generation of protein containers with properties custom-made for applications of interest.”

Among these applications might be fabricating nanoscale icosahedral vehicles. Such research might create tiny, spacecraft-like devices that could encapsulate and deliver therapies directly to specific types of cells, such as cancer cells.

The designed icosahedron, while sturdy, proved to disassemble and reassemble itself under certain environmental conditions. This reversible property is essential if it eventually becomes part of packaging, carrying and delivering a biochemical payload.

In addition, the flexibility to modify these miniature cages, the researchers said, “should have considerable utility for targeted drug delivery, vaccine design and synthetic biology.”

The newly designed icosahedron has considerably larger internal volume than previously designed nano-cages of other shapes, and so could hold more cargo as molecular shipping containers.

Working towards that end, the researchers were able to design barriers for the center of each of the twenty faces of the icosahedron. These could block molecules from entering and leaving the cage. In future iterations, gated cages might be filled to carry a medication into particular kinds of cell and then discharge it.

Moreover, the protein building blocks making up the cage retain their natural enzymatic activity, which is the ability to speed up chemical reactions. This suggests the possibility of custom designing them as nano-reactors to catalyze specific biochemical processes.

The nano-cages were, in addition, amenable to genetic fusions to enhance their properties. For example, the researchers created standard candles for light microscopy by adding a fluorescent protein to each of the 60 subunits that frame the icosahedron. The fluorescent intensity was proportional to the number of these proteins attached to each subunit. The distinctive shape of the icosahedron makes it a readily spotted marker.

This project was supported by the Howard Hughes Medical Institute, the JRC Visitor Program, the National Science Foundation, a University of Washington/Fred Hutchinson Cancer Research Institute Pilot Award from the National Cancer Institute, the Takeda Pharmaceutical Company, the Bill & Melinda Gates Foundation, the National Institutes of Health, and a Public Health Services National Research Services Award.

More information can be found from University of Washington website.

Siemens enters field of molecular services for oncology

Siemens Healthineers has expanded its diagnostics portfolio with the acquisition of NEO New Oncology AG, Cologne, Germany. The company's cancer genome diagnostic platform NEO(1) will support pathologists and oncologists with comprehensive molecular information to help select targeted cancer therapies. NEO New Oncology is developing molecular profiling assays based on NGS (Next Generation Sequencing), both for tissue specimens and body liquids. This includes NEOliquid, a liquid biopsy test for the analysis of genomic profiles of solid tumors from a simple blood sample. NEO New Oncology's high quality 3rd generation hybrid capture technology allows for the analysis of circulating tumor DNA with high accuracy.

The acquisition of NEO New Oncology provides Siemens Healthineers an entry point into NGS-based genomic testing and expands its capabilities in precision medicine and companion diagnostics. Furthermore, Siemens Healthineers establishes a business prospect in the field of molecular services, with the plan to provide testing and enablement services to physicians, hospitals and laboratories, including access to the latest medical knowledge and technologies.

A press release can be found from Siemens website by following this link.

Chemists use DNA to build the world’s tiniest thermometer

Researchers at University of Montreal have created a programmable DNA thermometer that is 20,000x smaller than a human hair. This scientific advance reported this week in the journal Nano Letters may significantly aid our understanding of natural and human designed nanotechnologies by enabling to measure temperature at the nanoscale.



Over 60 years ago, researchers discovered that the DNA molecules that encode our genetic information can unfold when heated. “In recent years, biochemists also discovered that biomolecules such as proteins or RNA (a molecule similar to DNA) are employed as nanothermometers in living organisms and report temperature variation by folding or unfolding,” says senior author Prof. Alexis Vallée-Bélisle. “Inspired by those natural nanothermometers, which are typically 20,000x smaller than a human hair, we have created various DNA structures that can fold and unfold at specifically defined temperatures.”

One of the main advantages of using DNA to engineer molecular thermometers is that DNA chemistry is relatively simple and programmable. “DNA is made from four different monomer molecules called nucleotides: nucleotide A binds weakly to nucleotide T, whereas nucleotide C binds strongly to nucleotide G,” explains David Gareau, first author of the study. “Using these simple design rules we are able to create DNA structures that fold and unfold at a specifically desired temperature.” “By adding optical reporters to these DNA structures, we can therefore create 5 nm-wide thermometers that produce an easily detectable signal as a function of temperature,” adds Arnaud Desrosiers, co-author of this study.

These nanoscale thermometers open many exciting avenues in the emerging field of nanotechnology, and may even help us to better understand molecular biology. “There are still many unanswered questions in biology,” adds Prof. Vallée-Bélisle, “For example, we know that the temperature inside the human body is maintained at 37° C, but we have no idea whether there is a large temperature variation at the nanoscale inside each individual cell.” One question currently under investigation by the research team is to determine whether nanomachines and nanomotors developed by nature over millions years of evolution also overheat when functioning at high rate. “In the near future, we also envision that these DNA-based nanothermometers may be implement in electronic-based devices in order to monitor local temperature variation at the nanoscale,” concludes Prof. Vallée-Bélisle.

More information can be found by following this link.

First computer program to detect DNA mutations in single cancer cells

Researchers at The University of Texas MD Anderson Cancer Center have announced a new method for detecting DNA mutations in a single cancer cell versus current technology that analyzes millions of cells which they believe could have important applications for cancer diagnosis and treatment. The results are published in the April 18 online issue of Nature Methods.

Existing technology, known as next-generation sequencing (NGS), measures genomes derived from millions of cells versus the newer method for single-cell sequencing, called Monovar. Developed by MD Anderson researchers, Monovar allows scientists to examine data from multiple single cells. The study was, in part, funded by MD Anderson’s Moon Shots Program, an unprecedented effort to significantly reduce deaths from cancer.

This led to development of newer technology, called single cell sequencing (SCS), that has had a major impact in many areas of biology, including cancer research, neurobiology, microbiology, and immunology, and has greatly improved understanding of certain tumor characteristics in cancer. Monovar improves further on the new SCS’s computational tools which scientists found “lacking” by more accurately detecting slight alterations in DNA makeup known as single nucleotide variants (SNVs).

Full news coverage can be found from  The University of Texas MD Anderson Cancer Center Website.