Raising strong yeast as a petroleum substitute

Strengthened Saccharomyces cerevisiae   
This common yeast is a strong contender for replacing petroleum in 2,3-butanediol production.   
Image Credit: Osaka Metropolitan University

As fossil fuels rise in cost and green initiatives gain traction, alternative methods for producing useful compounds using microorganisms have the potential to become sustainable, environmentally friendly technologies.

One such process involves the common bread yeast, Saccharomyces cerevisiae (S. cerevisiae), to produce 2,3-butanediol (2,3-BDO), an organic compound often used in pharmaceuticals and cosmetics. However, this yeast has a low tolerance for 2,3-BDO under high concentrations, which leads to a decline in its production ability and hinders the mass commercialization of this method.

What Is: Mitochondrion

Evolutionary Singularities and the Eukaryotic Dawn

The mitochondrion represents a biological singularity, a discrete evolutionary event that fundamentally partitioned life on Earth into two distinct energetic stratums: the prokaryotic and the eukaryotic. While colloquially reduced to the moniker of "cellular powerhouse," the mitochondrion is, in functional reality, a highly integrated endosymbiont that serves as the master regulator of eukaryotic physiology. It is the nexus of cellular respiration, the arbiter of programmed cell death, a buffer for intracellular calcium, and a hub for biosynthetic pathways ranging from heme synthesis to steroidogenesis. To comprehend the complexity of multicellular life, one must first dissect the intricate molecular sociology of this organelle.   

The origin of the mitochondrion is the subject of intense phylogenomic reconstruction. The prevailing consensus, the endosymbiotic theory, posits that the mitochondrion descends from a free-living bacterial ancestor—specifically a lineage within the Alphaproteobacteria—that entered into a symbiotic relationship with a host archaeal cell approximately 1.5 to 2 billion years ago. This was not a trivial acquisition but a transformative merger. The energetic capacity afforded by the internalization of a bioenergetic specialist allowed the host cell to escape the surface-area-to-volume constraints that limit prokaryotic genome size, facilitating the expansion of the nuclear genome and the development of complex intracellular compartmentalization. 

How the cheese-noodle principle could help counter Alzheimer's

Jinghui Luo is a researcher at the Center for Life Sciences at the Paul Scherrer Institute PSI. He studies accumulations of so-called amyloid proteins, which lead to nerve damage in the brain. His research aims to help mitigate neurodegenerative diseases such as Alzheimer's and Parkinson's in the long term.  Photo Credit: © Paul Scherrer Institute PSI/Markus Fischer

Researchers at the Paul Scherrer Institute PSI have clarified how spermine – a small molecule that regulates many processes in the body's cells – can guard against diseases such as Alzheimer's and Parkinson's: it renders certain proteins harmless by acting a bit like cheese on noodles, making them clump together. This discovery could help combat such diseases. The study has now been published in the journal Nature Communications.

Our life expectancy keeps rising – and as it does, age-related illnesses, including neurodegenerative diseases such as Alzheimer's and Parkinson's, become increasingly common. These diseases are caused by accumulations in the brain of harmful protein structures consisting of incorrectly folded amyloid proteins. Their shape is reminiscent of fibers or spaghetti. To date, there is no effective therapy to prevent or eliminate such accumulations. 

New type of DNA damage found in our cells’ powerhouses

Linlin Zhao (left) and Yu Hsuan Chen
Photo Credit: Courtesy of University of California, Riverside

A previously unknown type of DNA damage in the mitochondria, the tiny power plants inside our cells, could shed light on how our bodies sense and respond to stress. The findings of the UC Riverside-led study are published in the Proceedings of the National Academy of Sciences and have potential implications for a range of mitochondrial dysfunction-associated diseases, including cancer and diabetes. 

Mitochondria have their own genetic material, known as mitochondrial DNA (mtDNA), which is essential for producing the energy that powers our bodies and sending signals within and outside cells. While it has long been known that mtDNA is prone to damage, scientists didn't fully understand the biological processes. The new research identifies a culprit: glutathionylated DNA (GSH-DNA) adducts.

An adduct is bulky chemical tag formed when a chemical, such as a carcinogen, attaches directly to DNA. If the damage isn’t repaired, it can lead to DNA mutations and increase the risk of disease.

New switch for programmed cell death identified

During the analysis work: Prof. Franz Hagn (left) and Dr. Umut Günsel
Photo Credit: Astrid Eckert / TUM 

In the fight against disease, programmed cell death – also known as apoptosis – is a key protective function of the body. It breaks down cells that are damaged or have undergone dangerous changes. However, cancer cells often manage to override this mechanism. A research team at the Technical University of Munich (TUM) has now succeeded in identifying a new molecular switch in this process and elucidating how it works.

The activation and deactivation of apoptosis is a promising field of research in basic biomedical research. The team led by Prof. Franz Hagn from the Chair of Structural Membrane Biochemistry at the TUM School of Natural Sciences has now discovered a new switch: "Many research teams worldwide are working on the exciting topic of apoptosis and its targeted control. The big advantage is that we are dealing with a highly efficient, evolutionarily developed regulatory mechanism. So, we don't have to invent something completely new, but can use the appropriate structural methods to learn from nature's optimized processes."

The Many FACES of Lipid Research

Subcellular lipid distributions (magenta) in mitochondria (green) revealed using FACES and super-resolution structure illuminated microscopy.
Image Credit: William Moore

Lipids are fatty molecules that play critical roles in cell function, including membrane structure, energy storage and nutrient absorption. Most lipids are made in a cell organelle called the endoplasmic reticulum, but specific lipid types are shuttled around to different parts of the cell depending on their purpose. Each organelle serves a specific role in a cell and has its own unique mixture of lipids called a lipidome.

Scientists have long wanted to get a closer look at the movement of lipids around a cell, but because organelles are so close together – often only tens of nanometers apart – it’s tough to visualize with traditional light microscopy, which only has resolutions up to 250 nanometers.

Now researchers at the University of California San Diego have unveiled a new technology with the power to see cells in unprecedented detail. The tool, called fluorogen-activating coincidence encounter sensing (FACES), was developed in Associate Professor of Biochemistry & Molecular Biophysics Itay Budin’s lab. This work appears in Nature Chemical Biology.

Astrocytes, the unexpected conductors of brain networks

 

Dozens of synapses from distinct neural circuits gather around a specialised astrocyte structure called a leaflet, which is capable of detecting and integrating the activities of multiple synapses.
Image Credit: © Lucas BENOIT et Rémi GRECO/ GIN

A collaborative study between the Universities of Lausanne (UNIL) and Geneva (UNIGE), the Grenoble Institute of Neuroscience (GIN) and the Wyss Centre for Bio and Neuroengineering reveals a previously unknown role for astrocytes in the brain's processing of information. Published in the journal Cell, their study shows that these glial cells are capable of integrating and processing signals from several neurons at once. Using cutting-edge imaging techniques, the team identified new specialised structures called leaflets, which enable astrocytes to connect several neurons, and thus neural networks. This represents a conceptual shift in our understanding of the brain.

The brain does not function via neurons alone. In fact, nearly half of the cells that make up the brain are glial cells, and among them, astrocytes occupy a special place. Their name comes from their star-shaped skeleton, but their external appearance is more reminiscent of certain nebular stars, with an irregular, filamentary contour that allows them to insert themselves into the smallest gaps between neurons, blood vessels, and other cells. They are thus in close contact with synapses, the communication hubs between neurons.

A genome-wide atlas of cell morphology reveals gene functions

Human cells imaged using Cell Painting. Cell nuclei are shown in blue, actin filaments in yellow, the endoplasmic reticulum in magenta, golgi bodies in cyan, and mitochondria in green.
Image Credit: Maria Lozada, Neal Lab

Visualizing cells after editing specific genes can help scientists learn new details about the function of those genes. But using microscopy to do this at scale can be challenging, particularly when studying thousands of genes at a time.

Now, researchers at the Broad Institute of MIT and Harvard, along with collaborators at Calico Life Sciences, have developed an approach that brings the power of microscopy imaging to genome-scale CRISPR screens in a scalable way. 

PERISCOPE — which stands for perturbation effect readout in situ via single-cell optical phenotyping — combines two technologies developed by Broad scientists: Cell Painting, which can capture images and key measures of subcellular compartments at scale, and Optical Pooled Screening, which “barcodes” cells and uses CRISPR to systematically turn off individual genes to study their function in those cells. 

The new technique lets scientists study the effects of perturbing over 20,000 genes on hundreds of image-based cellular features. Generating data with this method is more than 10 times less expensive than comparable high-dimensional approaches such as high-throughput single-cell RNA sequencing and can be adapted to study a wide variety of cell types. In Nature Methods, the researchers applied PERISCOPE to execute three whole-genome CRISPR screens to create an open-source atlas of cell morphology.

Fueling nerve cell function and plasticity

The picture shows neurons (magenta) born in the adult mouse hippocampus. Nuclei are stained cyan. The extending dendrites are important sites where mechanisms of plasticity and competition for survival take place.
Photo Credit: Courtesy of ©Bergami Lab / University of Cologne

New finding from scientists at the University of Cologne discloses how mitochondria control tissue rejuvenation and synaptic plasticity in the adult mouse brain

Nerve cells (neurons) are amongst the most complex cell types in our body. They achieve this complexity during development by extending ramified branches called dendrites and axons and establishing thousands of synapses to form intricate networks. The production of most neurons is confined to embryonic development, yet few brain regions are exceptionally endowed with neurogenesis throughout adulthood. It is unclear how neurons born in these regions successfully mature and remain competitive to exert their functions within a fully formed organ. However, understanding these processes holds great potential for brain repair approaches during disease.

A team of researchers led by Professor Dr Matteo Bergami at the University of Cologne’s CECAD Cluster of Excellence in Aging Research addressed this question in mouse models, using a combination of imaging, viral tracing and electrophysiological techniques. They found that, as new neurons mature, their mitochondria (the cells’ power houses) along dendrites undergo a boost in fusion dynamics to acquire more elongated shapes. This process is key in sustaining the plasticity of new synapses and refining pre-existing brain circuits in response to complex experiences. The study ‘Enhanced mitochondrial fusion during a critical period of synaptic plasticity in adult-born neurons’ has been published in the journal Neuron.

New strategy to facilitate muscle regeneration after injury

From left to right, Ginés Viscor, Joan Ramon Torrella and Garoa Santocildes.
Photo Credit: Courtesy of University of Barcelona

Muscle injuries are common in the active population, and they cause the majority of player leaves in the world of sport. Depending on the severity, recovery of muscle function is quite slow and may require surgery, medication and rehabilitation. Now, a study led by the University of Barcelona reveals a strategy to improve and accelerate recovery from muscle injuries that has potential application in the sports and health sector in general.

This is the first study to provide scientific evidence for faster and more effective recovery from muscle injuries through intermittent exposure to low oxygen availability (hypoxia) in a low-barometric pressure (hypobaric) chamber that simulates high-altitude geographic conditions.

The new approach is important for the recovery of athletes — especially in the competitive elite — but also to mitigate the socio-economic impact of the loss of work productivity caused by these injuries on the active population.

The study, carried out with animal models, has been published in the Journal of Physiology. The authors of the study are the experts Garoa Santoildes, Teresa Pagès, Joan Ramon Torrella and Ginés Viscor, from the Department of Cell Biology, Physiology and Immunology of the UB’s Faculty of Biology.

3D model: This is how the body’s building blocks are made

Using electron microscopy, scientists have managed to produce a 3D model of a part of the human cell, the ribosome, which is no more than 30 nanometers in diameter.
Graphic Credit: Eva Kummer

Human cells contain ribosomes, a complex machine that produces proteins for the rest of the body. Now the researchers have come closer to understanding how the ribosome works.

“It is amazing that we can visualize the atomic details of the ribosome. Because they are tiny – around 20-30 nanometers.”

So says Associate Professor Eva Kummer from the Novo Nordisk Foundation Center for Protein Research, who is responsible for the new study published in Nature Communications.

And don’t worry if you don’t know how much a nanometer is. It is around one billionth of a meter.

Using electron microscopy, Eva Kummer and her colleagues Giang Nguyen and Christina Ritter have managed to produce a 3D model of a part of the human cell, the ribosome, which is no more than 30 nanometers in diameter.

More specifically, they have taken snapshots of how a ribosome is made.

“It is important to understand how the ribosome is built and how it works, because it is the only cell particle that produces proteins in humans and all other living organisms. And without proteins, life would cease to exist,” says Eva Kummer.

Proteins are the primary building blocks of the human body. Your heart, lungs, brain and basically your whole body is made of proteins produced by the ribosome.

“From the outside, the human body looks pretty simple, but then consider the fact that every part of the body consists of millions of molecules, that are extremely complex, and that they all know what to do – that is pretty breathtaking,” says Eva Kummer.

False Alarm of the Immune System during Muscle Disease

Prof. Claudia Günther (left) from Dresden and Prof. Eva Bartok (right) from Bonn are jointly investigating the connection between myotonic dystrophy and autoimmune diseases.
Photo Credit: © Universitätsklinikum Dresden & Universitätsklinikum Bonn

Researchers at the University Hospitals of Dresden and Bonn of the DFG Transregio 237 and from the Cluster of Excellence ImmunoSensation2 at the University of Bonn have made progress clarifying why patients with myotonic dystrophy 2 have a higher tendency to develop autoimmune diseases. Their goal is to understand the development of the disease, and their research has provided new, potential therapeutic targets. The results of the study have now been published in the renowned journal Nature Communications.

Myotonic dystrophy 2 (DM2) is a form of muscular dystrophy, a disease that leads to progressive muscle degeneration. It is caused by the expansion of a repetitive DNA sequence containing multiple CCTG bases in the CNBP gene. In general, the sequence of nucleobases in the DNA carries the genetic information. Patients suffer from muscle weakness that is more pronounced in the area of the muscles close to the trunk, as well as sustained muscle stiffness and pain. Although DM2 occurs in roughly one out of 10,000 people in Germany, there are no targeted therapies. In initial studies, Prof. Claudia Günther and her team at the Carl Gustav Carus University Hospital at the Technical University of Dresden also observed that patients with DM2 suffer more from autoimmune diseases with an increased production of antibodies in the blood than the general population. However, the underlying mechanism for these symptoms was previously unknown.

Mitochondrial activation in transplanted cells promotes regenerative therapy for heart healing

Regenerative therapy to treat heart failure is more effective when the mitochondria of the regenerative cells are activated prior to treatment.
Image Credit: Gemini Advance

Heart failure stands as a leading cause of mortality worldwide, demanding advanced treatment options. Despite the urgency for more effective treatments, options for severe heart failure remain limited. Cell transplantation therapy has emerged as a promising ray of hope, as it can be used in regenerative therapy to heal the heart.

A research team led by Professor Yuma Yamada of Hokkaido University’s Faculty of Pharmaceutical Science has developed a technique to promote cardiac regeneration by delivering mitochondrial activators to cardiac progenitor cells. Their findings were published in the Journal of Controlled Release.

“Cardiomyocytes efficiently use the mitochondrial tricarboxylic acid cycle to produce large amounts of adenosine triphosphate from several substrates via oxidative phosphorylation (OXPHOS),” explains Yamada. “Based on the energy metabolism of cardiomyocytes, we hypothesized that activating the mitochondrial function of transplanted cells may improve the outcome of cell transplantation therapy.”

Discovery: plants use “trojan horse” to fight mold invasions

Photo Credit: Gábor Adonyi

UC Riverside scientists have discovered a stealth molecular weapon that plants use to attack the cells of invading gray mold. 

If you’ve ever seen a fuzzy piece of fruit in your fridge, you’ve seen gray mold. It is an aggressive fungus that infects more than 1,400 different plant species: almost all fruits, vegetables, and many flowers. It is the second most damaging fungus for food crops in the world, causing billions in annual crop losses.

A new paper in the journal Cell Host & Microbe describes how plants send tiny, innocuous-seeming lipid “bubbles” filled with RNA across enemy lines, into the cells of the aggressive mold. Once inside, different types of RNA come out to suppress the infectious cells that sucked them in.

“Plants are not just sitting there doing nothing. They are trying to protect themselves from the mold, and now we have a better idea how they’re doing that,” said Hailing Jin, Microbiology & Plant Pathology Department professor at UCR and lead author of the new paper.

Previously, Jin’s team discovered that plants are using the bubbles, technically called extracellular vesicles, to send small RNA molecules able to silence genes that make the mold virulent. Now, the team has learned these bubbles can also contain messenger RNA, or mRNA, molecules that attack important cellular processes, including the functions of organelles in mold cells. 

Giant bacterium powers itself with unique processes

Micrograph of a group of Epulopiscium viviparus bacteria.
Image Credit: Esther Angert

Not all bacteria are created equal.

Most are single-celled and tiny, a few ten-thousandths of a centimeter long. But bacteria of the Epulopiscium family are large enough to be seen with the naked eye and 1 million times the volume of their better-known cousins, E. coli.

In a study published Dec. 18 in Proceedings of the National Academy of Sciences, researchers from Cornell and Lawrence Berkeley National Laboratory have for the first time described the full genome of one species of the family of giants, which they’ve named Epulopiscium viviparus.

“This incredible giant bacterium is unique and interesting in so many ways: its enormous size, its mode of reproduction, the methods by which it meets its metabolic needs and more,” said Esther Angert, professor of microbiology in the College of Agriculture and Life Sciences, and corresponding author of the study. “Revealing the genomic potential of this organism just kind of blew our minds.”

The first member of the Epulopiscium family was discovered in 1985. All members of the species live symbiotically within the intestinal tracts of certain surgeonfish in tropical marine coral reef environments, such as the Great Barrier Reef and in the Red Sea.

Preventing the Exhaustion of T Cells

Healthy (red) and exhausted (green) T cells in the spleen of chronically infected mouse.
Image Credit: Ana Maria Mansilla / Institut für Systemimmunologie, Universität Würzburg

In the immune system's fight against cancer and infections, the T cells often lose their power. The team of Würzburg immunologist Martin Vaeth has found a possible explanation for this phenomenon.

In the immune system, chronic infections and the defense against tumors often lead to the phenomenon of T cell exhaustion: In this process, the T lymphocytes gradually lose their function, which impairs their responses against cancer and infections. The molecular mechanisms that control this loss of function have not been fully unraveled.

It is now certain that the exhaustion process is significantly influenced by the “powerhouses of the cells”, the mitochondria.

When mitochondrial respiration fails, a cascade of reactions is triggered, culminating in the genetic and metabolic reprogramming of T cells – a process that drives their functional exhaustion. But this "burnout" of the T cells can be counteracted: pharmacological or genetic optimization of cellular metabolism increases the longevity and functionality of T cells. This can be achieved, for example, by overexpressing a mitochondrial phosphate transporter that drives the production of the energy-providing molecule adenosine-triphosphate.

High metabolism is an early sign of Alzheimer’s disease

Illustration Credit: geralt

An early phase in the process of developing Alzheimer’s disease is a metabolic increase in a part of the brain called the hippocampus, report researchers from Karolinska Institutet in a study published in Molecular Psychiatry. The discovery opens up new potential methods of early intervention.

Alzheimer’s disease is the most common form of dementia and strikes about 20,000 people in Sweden every year. Researchers now show that a metabolic increase in the mitochondria, the cellular power plants, is an early indicator of the disease. 

The teams behind the study used mice that developed Alzheimer’s disease pathology in a similar way to humans. The increase in metabolism in young mice was followed by synaptic changes caused by disruption to the cellular recycling system (a process known as autophagy), a finding that was awarded the Nobel Prize in Physiology or Medicine in 2016. 

After a time, metabolism in the Alzheimer brain usually declines, which contributes to the degradation of synapses. This the researchers could also see in the older mice, which had had the disease for a longer time. 

Researchers Show SARS-Cov-2 Infection Affects Energy Stores in the Body, Causing Organ Failure

Jonathan C. Schisler, PhD
Photo Credit: Courtesy of UNC

An international research team, including Jonathan C. Schisler, PhD, in the UNC School of Medicine, has found how SARS-CoV-2 causes widespread “energy outages” throughout major organs, and how these effects contribute to debilitating long COVID symptoms.

The lungs were once at the forefront of SARS-Cov-2 research, but as reports of organ failure and other serious complications poured in, scientists set out to discover how and why the respiratory virus was causing serious damage to the body’s major organs, including the lungs.

An interdisciplinary COVID-19 International Research Team (COV-IRT), which includes UNC School of Medicine’s Jonathan C. Schisler, PhD, found that SARS-CoV-2 alters mitochondria on a genetic level, leading to widespread “energy outages” throughout the body and its major organs. Their findings, published in Science Translational Medicine, explain how these effects contribute to long COVID symptoms and point to new therapeutic targets.

“We found that at peak infection time, there are distinct changes in different regions of the brain, including is a large decrease in mitochondrial genes in the cerebellum, the part of the brain that controls our muscles, balance, cognition, and emotion” said Schisler, assistant professor of pharmacology and member of the UNC McAllister Heart Institute. “The lung is the primary site of infection, but molecular signals are being transmitted affecting the entire body, with the heart, kidney, and liver being more affected than others, even long after the virus is gone.”

Discovery reveals fragile X syndrome begins developing even before birth

The energy-making organelles called mitochondria (shown in green) that work inside cells to make energy aren’t working as they should in the neurons (shown in red) of people with fragile X syndrome. UW–Madison researchers have identified a protein and gene involved in this mitochondrial dysfunction, as well as a potential treatment.
Image Credit: Minjie Shen

Fragile X syndrome, the most common form of inherited intellectual disability, may be unfolding in brain cells even before birth, despite typically going undiagnosed until age 3 or later.

A new study published today in the journal Neuron by researchers at the University of Wisconsin–Madison showed that FMRP, a protein deficient in individuals with fragile X syndrome, has a role in the function of mitochondria, part of a cell that produces energy, during prenatal development. Their results fundamentally change how scientists understand the developmental origins of fragile X syndrome and suggest a potential treatment for brain cells damaged by the dysfunction.

Xinyu Zhao is a neuroscience professor and neurodevelopmental diseases researcher at UW–Madison’s Waisman Center. Four postdoctoral fellows in her lab led the study.

Researchers catch protons in the act of dissociation with SLAC’s ultrafast 'electron camera'

Irradiating ammonia – which is made up of one nitrogen and three hydrogens – with ultraviolet light causes one hydrogen to dissociate from the ammonia. SLAC researchers used an ultrafast “electron camera” to watch exactly what that hydrogen was doing as it dissociated. The technique had been proposed, but never proven to work, until now. In the future, researchers could use the technique to study hydrogen transfers – critical chemical reactions that drive many biological processes.
Illustration Credit: Nanna H. List/KTH Royal Institute of Technology

Scientists have caught fast-moving hydrogen atoms – the keys to countless biological and chemical reactions – in action.

A team led by researchers at the Department of Energy’s SLAC National Accelerator Laboratory and Stanford University used ultrafast electron diffraction (UED) to record the motion of hydrogen atoms within ammonia molecules. Others had theorized they could track hydrogen atoms with electron diffraction, but until now nobody had done the experiment successfully.

The results, published in Physical Review Letters, leverage the strengths of high-energy Megaelectronvolt (MeV) electrons for studying hydrogen atoms and proton transfers, in which the singular proton that makes up the nucleus of a hydrogen atom moves from one molecule to another.  

Proton transfers drive countless reactions in biology and chemistry – think enzymes, which help catalyze biochemical reactions, and proton pumps, which are essential to mitochondria, the powerhouses of cells – so it would be helpful to know exactly how its structure evolves during those reactions. But proton transfers happen super-fast – within a few femtoseconds, one millionth of one billionth of one second. It’s challenging to catch them in action.