'Zombie' replica cells may outperform live ones as catalysts and conductors

"Zombie" mammalian cells that may function better after they die have been created by researchers at Sandia National Laboratories and the University of New Mexico (UNM).

The simple technique coats a cell with a silica solution to form a near-perfect replica of its structure. The process may simplify a wide variety of commercial fabrication processes from the nano- to macroscale.

The work, reported in the Proceedings of the National Academy of Sciences (PNAS), uses the nanoscopic organelles and other tiny components of mammalian cells as fragile templates on which to deposit silica. The researchers then heat the cell to burn off its protein. The resultant hardened silica structures are faithful to the exterior and interior features of the formerly living cell, can survive greater pressures and temperatures than flesh ever could, and can perform some functions better than when they were alive, said lead researcher Bryan Kaehr, a Sandia materials scientist.

"It’s very challenging for researchers to build structures at the nanometer scale," said Kaehr. "We can make particles and wires, but 3-D arbitrary structures haven’t been achieved yet. With this technique, we don’t need to build those structures—nature does it for us. We only need to find cells that possess the machinery we want and copy it using our technique. And, using chemistry or surface patterning, we can program a group of cells to form whatever shape seems desirable."

UNM professor and Sandia Fellow Jeff Brinker added, “The process faithfully replicates features from the nanoscale to macroscale in a robust, three-dimensionally stable form that resists shrinkage even upon heating to over 500 degrees Centigrade [932 degrees Fahrenheit]. The refractoriness of these delicate structures is amazing.”

Solving Stem Cell Mysteries

The ability of embryonic stem cells to differentiate into different types of cells with different functions is regulated and maintained by a complex series of chemical interactions, which are not well understood. Learning more about this process could prove useful for stem cell-based therapies down the road. New research from a team led by Carnegie’s Yixian Zheng zeroes in on the process by which stem cells maintain their proper undifferentiated state. Their results are published in Cell October 26.

Embryonic stem cells go through a process called self-renewal, wherein they undergo multiple cycles of division while not differentiating into any other type of cells. This process is dependent on three protein networks, which guide both self-renewal and eventual differentiation. But the integration of these three networks has remained a mystery.

Using a combination of genetic, protein-oriented and physiological approaches involving mouse embryonic stem cells, the team—which also included current and former Carnegie scientists Junling Jia, Xiaobin Zheng, Junqi Zhang, Anying Zhang, and Hao Jiang—uncovered a mechanism that integrates all three networks involved in embryonic stem cell self-renewal and provide a critical missing link to understanding this process.

The key is a protein called Utf1. It serves three important roles. First, it balances between activating and deactivating the necessary genes to direct the cell toward differentiation. At the same time, it acts on messenger RNA that is the transcription product of the genes when they’re activated by tagging it for degradation, rather than allowing it to continue to serve its cellular function. Lastly, it blocks a genetic feedback loop that normally inhibits cellular proliferation, allowing it to occur in the rapid nature characteristic of embryonic stem cells.

Target for obesity drugs comes into focus

Researchers at the University of Michigan have determined how the hormone leptin, an important regulator of metabolism and body weight, interacts with a key receptor in the brain.

Leptin is a hormone secreted by fat tissue that has been of interest for researchers in obesity and Type 2 diabetes since it was discovered in 1995. Like insulin, leptin is part of a regulatory network that controls intake and expenditure of energy in the body, and a lack of leptin or resistance to it has been linked to obesity in people.

Although there can be several complex reasons behind leptin resistance, in some cases the underlying cause is malfunction of the leptin receptor in the brain. An understanding of how leptin and its receptor interact could lead to new treatments for obesity and metabolic disorders, but the structure of this signaling complex has evaded researchers for years.

Georgios Skiniotis, a faculty member at the Life Sciences Institute and assistant professor in biological chemistry at the U-M Medical School, employed electron microscopy to obtain the first picture of the interaction between leptin and its receptor.

Skiniotis also traced similarities between the leptin receptor and other receptors of the same family, which may provide insight into new targets for treatment of other hormone-related diseases.

A molecular scissor related to Alzheimer’s Disease

An international research team led by the Spanish National Research Council (CSIC) and researchers from Kiel University revealed the atomic-level structure of the human peptidase enzyme meprin ß (beta). The enzyme is related to inflammation, cancer and Alzheimer’s Disease and is involved in cellular proliferation and differentiation. The knowledge of the enzyme structure will allow for the development of a new medication type different from those known up to now. The study was published in the current issue of the journal “Proceedings of the National Academy of Sciences”.

“Now that we know how meprin ß looks, how it works and how it relates to diseases, we can search for substances that stop its enzyme activities when they become harmful”, explains Xavier Gomis-Rüth, researcher at the Molecular Biology Institute of Barcelona, who led the project. Meprin ß is an enzyme that is anchored in the outer wall of cells. Its normal function in the human metabolism is to cut off certain proteins, e.g. growth factors, that are also anchored in the cell wall. In this way meprin ß releases protein fragments into the environment surrounding the cells – a natural and normal process, as long as it occurs at a certain intensity. However, under specific circumstances, meprin ß may function abnormally, and, for example, releases too many protein fragments. The protein pieces than overdo their natural task in the cell surroundings, causing disorder in the human body. Such disorder typically occurs when inflammation, cancer or Alzheimer’s Disease get started.

The first detailed and complete picture of a protein complex that is tied to human birth defects as well as the progression of many forms of cancer has been obtained by an international team of researchers led by scientists with the U.S. Department of Energy (DOE)’s Lawrence Berkeley National Laboratory (Berkeley Lab). Knowing the architecture of this protein, PRC2, for Polycomb Repressive Complex 2, should be a boon to its future use in the development of new and improved therapeutic drugs.

Proteins adorning the surfaces of human cells perform an array of essential functions, including cell signaling, communication and the transport of vital substances into and out of cells. They are critical targets for drug delivery and many proteins are now being identified as disease biomarkers—early warning beacons announcing the pre-symptomatic presence of cancers and other diseases.

While study of the binding properties of membrane proteins is essential, detailed analysis of these complex entities is tricky. Now, Nongjian (NJ) Tao, Professor of Electrical Engineering, and director of the Center for Bioelectronics and Biosensors at Arizona State University’s Biodesign Institute has devised a new technique for examining the binding kinetics of membrane proteins.

“This is a very important but very difficult problem to solve,” Tao notes. “We demonstrate a new method of approaching the issue, which provides a quantitative analysis of protein interactions on the surface of a cell.”

The technique—known as SPR microscopy—holds the potential to simplify the study of membrane proteins, thereby streamlining the development of new drugs, aiding the identification of diagnostic biomarkers and improving the understanding of cell-pathogen interactions.

The group’s results appear in this week’s advanced online issue of the journal Nature Chemistry.

The human microbiome: Me, myself, us

Looking at human beings as ecosystems that contain many collaborating and competing species could change the practice of medicine.

A human being is an individual who has grown from a fertilised egg which contained genes from both father and mother. A growing band of biologists, however, think this definition incomplete. They see people not just as individuals, but also as ecosystems. In their view, the descendant of the fertilised egg is merely one component of the system. The others are trillions of bacteria, each equally an individual, which are found in a person’s gut, his mouth, his scalp, his skin and all of the crevices and orifices that subtend from his body’s surface.

A healthy adult human harbours some 100 trillion bacteria in his gut alone. That is ten times as many bacterial cells as he has cells descended from the sperm and egg of his parents. These bugs, moreover, are diverse. Egg and sperm provide about 23,000 different genes. The microbiome, as the body’s commensal bacteria are collectively known, is reckoned to have around 3m. Admittedly, many of those millions are variations on common themes, but equally many are not, and even the number of those that are adds something to the body’s genetic mix.

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