GN/ Nearly dead plants brought back to life: Keys to aging hidden in the leaves
Genetics biweekly vol.50, 13th January — 1st February
TL;DR
- Scientists have known about a particular organelle in plant cells for over a century. However, scientists have only now discovered that organelle’s key role in aging.
- Researchers have used DNA origami, the art of folding DNA into desired structures, to show how an important cell receptor can be activated in a previously unknown way. The result opens new avenues for understanding how the Notch signalling pathway works and how it is involved in several serious diseases.
- Research group has elucidated a so-far enigmatic, exceptional secretion mechanism, that allows the release of the gigantic Tc toxins. In a kind of kamikaze attack, a small group of so-called “soldier” bacteria, packed to the brim with toxins, release their deadly cargo by exploding in the host. Targeting such subpopulations in medical therapies could be a promising treatment strategy for diseases triggered by bacteria that are becoming increasingly resistant to antibiotics.
- A team of scientists discovered the secrets of cell variability in our bodies. The findings of this research are expected to have far-reaching effects, such as improvement in the efficacy of chemotherapy treatments, or set a new paradigm in the study of antibiotic-resistant bacteria.
- The repair of damage to genetic material (DNA) in the human body is carried out by highly efficient mechanisms that have not yet been fully researched. A scientific team has now discovered a previously unrecognized control point for these processes. This could lead to a new approach for the development of cancer therapies aimed at inhibiting the repair of damaged cancer cells.
- An international team of researchers has uncovered a remarkable genetic phenomenon in lycophytes, which are similar to ferns and among the oldest land plants. Their study reveals that these plants have maintained a consistent genetic structure for over 350 million years, a significant deviation from the norm in plant genetics.
- In a new study, researchers have discovered how a system of proteins, called TamAB, helps Salmonella survive under the harsh conditions inside macrophages.
- Researchers have engineered one of the world’s first yeast cells able to harness energy from light, expanding our understanding of the evolution of this trait — and paving the way for advancements in biofuel production and cellular aging.
- To function properly, the genetic material is highly organized into loop structures that often bring together widely separated sections of the genome critical to the regulation of gene activity. Scientists now address how these loops can help repress or silence gene activity, with potentially far-reaching effects on human health.
- With human retinas grown in a petri dish, researchers discovered how an offshoot of vitamin A generates the specialized cells that enable people to see millions of colors, an ability that dogs, cats, and other mammals do not possess.
- And more!
Overview
Genetic technology is defined as the term which includes a range of activities concerned with the understanding of gene expression, advantages of natural genetic variation, modifying genes and transferring genes to new hosts. Genes are found in all living organisms and are transferred from one generation to the next. Gene technology encompasses several techniques including marker-assisted breeding, RNAi and genetic modification. Only some gene technologies produce genetically modified organisms.
Modern genetic technologies like genome editing would not be possible without all the previous generations of genetic technologies that have enabled scientists to discover what genes are, what they do and how DNA can be modified to add, remove or replace genes. You can find major genetic technologies development milestones via the link.
Gene Technology Market
- The valuation of the genetic engineering market is projected to escalate to USD 6.90 MN by the end of 2027.
- Global Genetic Engineering Market is projected to grow at 12.48% CAGR during the assessment period (2017–2027).
- North America holds the largest share in the global genetic engineering market, followed by Europe and the Asia Pacific, respectively.
Latest News & Research
COG-imposed Golgi functional integrity determines the onset of dark-induced senescence
by Hee-Seung Choi, Marta Bjornson, Jiubo Liang, Jinzheng Wang, Haiyan Ke, Manhoi Hur, Amancio De Souza, Kavitha Satish Kumar, Jenny C. Mortimer, Katayoon Dehesh in Nature Plants
Scientists have known about a particular organelle in plant cells for over a century. However, UC Riverside scientists have only now discovered that organelle’s key role in aging.
The researchers initially set out to understand more generally which parts of plant cells control plant responses to stress from things like infections, too much salt, or too little light. Serendipitously, they found this organelle, and a protein responsible for maintaining the organelle, control whether plants survive being left too often in the dark. Because they had not expected this discovery, the research team was thrilled.
“For us, this finding is a big deal. For the first time, we have defined the profound importance of an organelle in the cell that was not previously implicated in the process of aging,” said Katie Dehesh, distinguished professor of molecular biochemistry at UCR and co-author of the new article.
Sometimes described as appearing like a stack of deflated balloons or some dropped lasagna, the organelle called the Golgi body is composed of a series of cup-shaped membrane-covered sacs. It sorts various molecules in the cell and ensures they get to the right places.
“Golgi are like the post office of the cell. They package and send out proteins and lipids to where they’re needed,” said Heeseung Choi, a researcher in UCR’s Botany and Plant Sciences Department and co-author of the new study. “A damaged Golgi can create confusion and trouble in the cell’s activities, affecting how the cell works and stays healthy.”
If the Golgi is the post office, then the COG protein is the postal worker. This protein controls and coordinates the movement of small sac “envelopes” that transport other molecules around the cell. Additionally, COG helps Golgi bodies attach sugars to other proteins or lipids before they are sent elsewhere in the cell. This sugar modification, called glycosylation, is crucial for many biological processes, including immune response.
To learn more about how COG affects plant cells, the research team modified some plants so that they could not produce it. Under normal growing conditions, the modified plants grew just fine, and were indistinguishable from unmodified plants. However, depriving plants of light means plants are unable to make sugar from sunlight to fuel growth. When exposed to excessive darkness the leaves of the mutant, COG-free plants began to turn yellow, wrinkled, and thin — signs the plants were dying.
“In the dark, the COG mutants showed signs of aging that typically appear in wild, unmodified plants around day nine. But in the mutants, these signs manifested in just three days,” Choi said.
Reversing the mutation and returning the COG protein back into the plants rapidly brought them back to life. “It’s like nothing happened to them once we reversed the mutation,” Dehesh said. “These responses highlight the critical importance of the COG protein and normal Golgi function in stress management,” Choi added.
Part of the excitement surrounding this discovery is that humans, plants, and all eukaryotic organisms have Golgi bodies in their cells. Now, plants can serve as a platform to explore the intricacies of the Golgi’s role in human aging. For this reason, the research team is planning further studies of the molecular mechanisms behind the results from this study.
“Not only does our research advance our knowledge about how plants age, but it could also provide crucial clues about aging in humans,” Dehesh said. “When the COG protein complex doesn’t work properly, it might make our cells age faster, just like what we saw in plants when they lacked light. This breakthrough could have far-reaching implications for the study of aging and age-related diseases.”
Soluble and multivalent Jag1 DNA origami nanopatterns activate Notch without pulling force
by Ioanna Smyrlaki, Ferenc Fördős, Iris Rocamonde-Lago, Yang Wang, Boxuan Shen, Antonio Lentini, Vincent C. Luca, Björn Reinius, Ana I. Teixeira, Björn Högberg in Nature Communications
Researchers at Karolinska Institutet in Sweden have used DNA origami, the art of folding DNA into desired structures, to show how an important cell receptor can be activated in a previously unknown way. The result opens new avenues for understanding how the Notch signalling pathway works and how it is involved in several serious diseases.
Notch is a cell receptor that is of great importance to a wide range of organisms and plays a crucial role in many different processes, including early embryonic development in both flies and humans. Notch regulates the development of stem cells into different cell types in the body. Defects in this signalling pathway can result in serious diseases, including cancer.
The prevailing view of the receptor’s function has so far been that it is activated purely mechanically, by a neighbouring cell pulling on it, meaning that signalling only occurs as a result of direct communication between cells. However, researchers at Karolinska Institutet now report that the activation of Notch can also be achieved ‘on demand’ with the help of a protein called Jag1. The researchers placed the protein on a DNA structure created by so-called DNA origami, a technique that makes it possible to build structures of any shape at the nanoscale using DNA as a building material. In this case, the DNA structure was moulded into a nano-sized stick that can carry the protein to the cell surface.
“This is a technique that allows us to place molecules of the Jag1 protein at very small distances from each other in different patterns, and then we have exposed these patterns to stem cells with Notch receptors,” says Björn Högberg, professor at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, who led the study together with KI researcher Ioanna Smyrlaki at the same department.
The results show that the Notch receptor can be activated to different degrees, depending on the shape of the pattern and the local concentration of the protein. However, several questions remain about how exactly this signalling takes place.
“We are now collaborating with other researchers to see if we can make this method work in vivo as well, i.e. in a mouse model and not just in test tubes,” says Björn Högberg. “This is basic research, but Notch is an important component in several diseases, including a form of leukaemia and the developmental disorder Alagille Syndrome. We therefore hope that the results will also lead to a better understanding of these diseases.”
Yersinia entomophaga Tc toxin is released by T10SS-dependent lysis of specialized cell subpopulations
by Oleg Sitsel, Zhexin Wang, Petra Janning, Lara Kroczek, Thorsten Wagner, Stefan Raunser in Nature Microbiology
You suddenly feel sick — pathogenic bacteria have managed to colonize and spread in your body! The weapons they use for their invasion are harmful toxins that target the host’s defense mechanisms and vital cell functions. Before these deadly toxins can attack host cells, bacteria must first export them from their production site — the cytoplasm — using dedicated secretion systems. The group of Stefan Raunser, Director at the Max Planck Institute of Molecular Physiology, has now elucidated a so-far enigmatic, exceptional secretion mechanism, that allows the release of the gigantic Tc toxins. In a kind of kamikaze attack, a small group of so-called “soldier” bacteria, packed to the brim with toxins, release their deadly cargo by exploding in the host. Targeting such subpopulations in medical therapies could be a promising treatment strategy for diseases triggered by bacteria that are becoming increasingly resistant to antibiotics.
Once a pathogenic bacterium has entered its host, it turns on a series of defense and attack mechanisms to spread, invade and colonize deeper tissues and organs. This includes the secretion of an array of toxic proteins that subvert the host’s cellular defenses. In gram-negative bacteria, which can trigger severe infections and are becoming increasingly resistant to antibiotics, toxic proteins face the challenge of crossing several cellular barriers — belonging to both the bacteria and the host — to finally reach their destination. To this end, bacteria have developed a number of specialized secretion systems.
Some can secrete a variety of toxins and are found in almost all bacteria, while others have been identified in only few bacteria. The machinery for the secretion of many smaller toxins has already been established. Not so for larger ones, like the Tc toxins produced by the notorious Yersinia bacteria, which also include pathogens that cause plague and tuberculosis.
“It has remained enigmatic for decades how the huge Tc toxins reach their final destination. By obtaining the first 3D structures of a Tc toxin in our previous electron cryomicroscopy studies we could already figure out how it bypasses the last barrier, the host membrane, using a syringe-like injection mechanism. Now, we were able to complete the picture and show how these toxins overcome the three barriers separating the inside of the bacteria from its environment in a truly spectacular way,” says Stefan Raunser.
In their recent work, Raunser and his team have applied a cutting-edge combination of several techniques to investigate the secretion of the Tc toxin YenTc produced by the insect pathogen Yersinia entomophaga, which is crucial for this bacterial species to establish an infection. The biggest challenge was to initially identify which of the known secretion machineries is used for this purpose by the bacteria. To this end, the scientists knocked out all suspected secretion systems one after the other using targeted genome editing. When none of the knockouts stopped the toxin’s release, the same technique was used to modify the toxin so that its secretion could be visualized — and this time with success. “Watching some of the bacteria literally explode to release their toxins was a real eureka moment,” says Oleg Sitsel, first author of the study. Careful proteomic analysis then finally brought to light a pH-sensitive type 10 secretion system responsible for toxin release, a class of protein export machinery that was just recently established. Subsequent cryo-electron tomographic analysis visualized the step-by-step details of how this secretion system exports cellular contents via a previously unknown lytic mode of action that overcomes the three barriers surrounding gram-negative bacteria.
The scientists found that only a small specialized subset of bacterial cells produces and exports the toxins by paying the ultimate price, namely death. But what causes those cells, which the authors termed “soldier cells,” to first enlarge and produce a deadly toxin cocktail containing YenTc, then commit suicide for the benefit of their comrades? The scientists first determined that the appearance of soldier cells is temperature-, nutrient- and cell density-dependent. They then discovered a temperature-sensitive genetic switch that synchronizes the production of the toxins with the production of the secretion system, and turns “normal” cells into their soldier brethren. The mass production of toxins coupled to the cells’ enlarged size ensures that only few individuals need to be sacrificed for the greater good of the bacterial population, an extremely efficient strategy.
“We suspect that normal cells turn into soldier cells upon ingestion in response to insect host nutrients. Toxin secretion is pH sensitive, which delays its release until the soldier cells reach the alkaline posterior midgut, their major theatre of operations,” says Raunser.
“This secretion strategy is unique and remarkable. The behaviour of these bacteria exhibits characteristics such as differentiation and altruism, which are reminiscent of eusocial systems. If this turns out to be a more common mechanism, we might have exposed a weak point in bacteria: specifically targeting the soldier cells could become a promising medical strategy in the fight against pathogenic bacteria, especially in times of increasing resistance to antibiotics,” concludes Raunser.
Density physics-informed neural networks reveal sources of cell heterogeneity in signal transduction
by Hyeontae Jo, Hyukpyo Hong, Hyung Ju Hwang, Won Chang, Jae Kyoung Kim in Patterns
A team of South Korean scientists led by Professor KIM Jae Kyoung of the Biomedical Mathematics Group within the Institute for Basic Science (IBS-BIMAG) discovered the secrets of cell variability in our bodies. The findings of this research are expected to have far-reaching effects, such as improvement in the efficacy of chemotherapy treatments, or set a new paradigm in the study of antibiotic-resistant bacteria.
The cells in our body have a signaling system that responds to various external stimuli such as antibiotics and osmotic pressure changes. This signaling system plays a critical role in the survival of cells as they interact with the external environment. However, even cells with same genetic information can respond differently to the same external stimuli, called cellular heterogeneity.
Cellular heterogeneity is a great research interest in medicine, as it is known to hinder the complete eradication of cancer cells by chemotherapeutic agents such as anticancer drugs. The sources of such heterogeneity and its relationship with the signaling system have remained a challenge, as intermediate processes of the signaling system are impossible to fully observe with current experimental technology.
To reveal the sources of this heterogeneity, Professor Kim’s research team developed a machine learning methodology using artificial neural network structures called Density Physics-informed neural networks (Density-PINNs). Density-PINNs use the observable time-series data of cells’ responses to external stimuli to inversely estimate information about the signaling system. By applying Density-PINNs to actual experimental data of antibiotic responses of bacterial cells (Escherichia coli), the research team found that a parallel structure of the signaling system can reduce heterogeneity among cells.
Professor Kim believes that this mathematical modeling and machine learning research will facilitate the enhancement of the understanding of cellular heterogeneity, which is crucial in cancer treatment. He expressed his hope that this achievement would lead to the development of improved cancer treatment strategies.
GSE1 links the HDAC1/CoREST co-repressor complex to DNA damage
by Terezia Vcelkova, Wolfgang Reiter, Martha Zylka, David M Hollenstein, Stefan Schuckert, Markus Hartl, Christian Seiser in Nucleic Acids Research
The repair of damage to genetic material (DNA) in the human body is carried out by highly efficient mechanisms that have not yet been fully researched. A scientific team led by Christian Seiser from MedUni Vienna’s Center for Anatomy and Cell Biology has now discovered a previously unrecognised control point for these processes. This could lead to a new approach for the development of cancer therapies aimed at inhibiting the repair of damaged cancer cells. T
GSE1-CoREST is the name of the newly discovered complex, which contains three enzymes that control DNA repair processes and could form the basis for novel cancer therapeutics. “In research, these proteins are already associated with cancer, but not in the context that we have now found,” emphasises Christian Seiser, who led the study in close collaboration with researchers from the Max Perutz Labs Vienna. The new complex was identified as a controller of DNA repair processes using a precise measurement method (affinity purification mass spectrometry).
“This also showed that the inhibition of these enzymes can prevent the repair of genetic material and cause the death of cells,” says first author Terezia Vcelkova from MedUni Vienna’s Center for Anatomy and Cell Biology describing a highly desirable effect in tumour cells.
The genetic material, the DNA, is exposed to various harmful influences such as UV light or environmental pollutants on a daily basis. These influences can lead to changes in the DNA sequence, so-called mutations. To repair this damage to genetic material, various highly efficient biochemical repair mechanisms are normally activated. If these processes do not succeed in repairing the damage, programmed cell death (apoptosis) is ultimately initiated to protect against malignant cells.
To ensure their survival, cells react to DNA damage by activating and integrating signalling pathways or signalling cascades. This is achieved in particular through the activation of signalling pathways known as DNA damage response (or DDR). These signalling cascades are responsible for bringing repair factors to the right place in the genome at the right time in order to repair the mutated DNA efficiently and promptly. The control instances and regulators in this interaction are better defined thanks to the current research work.
“The effectiveness of the novel cancer therapeutics based on this, which are intended to improve the response of tumour cells to cancer therapies, is now being tested in preclinical studies,” says Christian Seiser about the next steps.
Extraordinary preservation of gene collinearity over three hundred million years revealed in homosporous lycophytes
by Cheng Li, David Wickell, Li-Yaung Kuo, Xueqing Chen, et al in Proceedings of the National Academy of Sciences
An international team of researchers has uncovered a remarkable genetic phenomenon in lycophytes, which are similar to ferns and among the oldest land plants. Their study reveals that these plants have maintained a consistent genetic structure for over 350 million years, a significant deviation from the norm in plant genetics.
“The exceptionally slow pace of genomic evolution sets these plants apart,” said Dr. Fay-Wei Li, a professor at the Boyce Thompson Institute and a senior author of the study. “Understanding why these plants have changed so little could reveal important aspects of plant evolution and genetics.”
Homosporous lycophytes, a group of seedless vascular plants, show extraordinary genomic stability. The team sequenced the genomes of two species, Huperzia asiatica and Diphasiastrum complanatum, which diverged from a common ancestor about 350 million years ago (approximately when amphibians started to crawl onto land). Surprisingly, it was discovered that about 30% of their genes have remained in the same arrangement since their divergence, exhibiting an unusual evolutionary pattern known as synteny.
“This study opens a window into the past, showing us how remarkably stable the genetic makeup of these plants has been,” said Dr. Li Wang, co-author of the study. “It’s like finding a living fossil at the genetic level.”
The scientists also observed a notable retention of duplicated gene copies following whole genome duplication events, which is unusual. “While a handful of duplicate genes may evolve new roles, the vast majority are lost relatively quickly through a process known as diploidization,” explains Dr. David Wickell, post-doctoral researcher and co-first author of the study. However, the researchers found that these homosporous lycophytes often retained both sets of genes with relatively few alterations, even after hundreds of millions of years of evolution.
“That homosporous lycophytes have retained so many duplicate genes and so much synteny is fascinating, a little bit surprising, and doesn’t necessarily fit with our traditional ideas of how genomes reorganize themselves after a large-scale duplication,” notes Wickell. “While it’s still unclear precisely what is driving this difference, we believe that further study of homosporous plants has the potential to provide novel insights into plant genetics and evolution across all land plants. It also underscores the importance of preserving biodiversity, as these amazing plants hold vital clues to the history of life on Earth.”
TamAB is regulated by PhoPQ and functions in outer membrane homeostasis during Salmonella pathogenesis
by Rouhallah Ramezanifard, Yekaterina A. Golubeva, Alexander D. Palmer, James M. Slauch in Journal of Bacteriology
Salmonella is notorious for surviving and replicating in macrophages, which are normally lethal to invading bacteria because of their inhospitable environment. In a new study, researchers have discovered how a system of proteins, called TamAB, helps Salmonella survive under the harsh conditions inside macrophages.
Salmonella is a foodborne pathogen that causes more than a million infections each year in the U.S. Concerningly, it can kill young, old, and immunocompromised individuals. What makes these bacteria especially dangerous is their ability to evade our immune responses.
Macrophages are designed to kill bacteria by spraying them with antibacterial products, exposing them to acidic environments, and withholding magnesium, all of which target the outer layers of the bacteria. Salmonella, however, has evolved mechanisms to survive and grow in this environment.
Under normal conditions, Salmonella uses a complex called Bam to assemble certain proteins that are transported to its outer membrane layer. In previous studies, the group have shown that inside macrophages, the complex is compromised and, as a result, Salmonella depends on the PhoPQ system to sense the environment and orchestrate necessary changes in the outer membrane.
Studies in other bacteria have shown that the TamAB complex performs similar functions to Bam, which led the researchers of the present study to ask whether it might be important in Salmonella. They found that the genes that were responsible for producing TamAB were being controlled by PhoPQ.
“We knew from other studies that TamA was similar to BamA in its structure. When we realized that PhoPQ was controlling this TamAB complex, we hypothesized that the Bam complex struggles in the macrophage and TamA is induced by PhoPQ to help,” said James Slauch (IGOH), a professor of microbiology.
To test their hypothesis, the researchers first removed TamAB from Salmonella. To their surprise, these mutants were still able to cause an infection in mice. However, when they also crippled the Bam complex, the mutants that lacked TamAB struggled.
The researchers also saw similar results when they recreated the macrophage-like conditions in test tubes and tested the different Salmonella mutants. They observed that mutants that lacked both the Bam and TamAB complexes were sensitive to vancomycin. This result is particularly intriguing because vancomycin is not used to treat Salmonella since it can’t cross the outer membrane. This sensitivity suggests that the two complexes have a function in creating or maintaining the outer membrane, although the mechanism is not clear.
“Basically, TamAB helps create favorable conditions for the Bam complex to work but it’s indirect,” said Yekaterina Golubeva, a research scientist in the Slauch lab.
It is still unclear what the indirect effect might be. “The problem is that studying the outer membrane is complicated because everything is interconnected. If you mess up the Bam complex, it disrupts additional machineries required for synthesis of the outer membrane. As a result, understanding the contributions of these proteins is difficult,” Slauch said.
Nonetheless, the researchers are now interested in figuring out how TamAB helps. To do so, they will be using suppressor mutants that have accumulated different types of mutations that can help them grow even if their Bam and Tam complexes are defective, providing insights into Salmonella’s outer membrane structure and function.
“There are efforts underway in biotechnology companies that are targeting the Bam complex as a way to treat Salmonella infections,” Slauch said. “Understanding the structure of the outer membrane when Salmonella is in a macrophage can help us understand what will affect its sensitivity to drugs and our results with vancomycin is consistent with that.”
Transforming yeast into a facultative photoheterotroph via expression of vacuolar rhodopsin
by Autumn Peterson, Carina Baskett, William C. Ratcliff, Anthony Burnetti in Current Biology
You may be familiar with yeast as the organism content to turn carbs into products like bread and beer when left to ferment in the dark. In these cases, exposure to light can hinder or even spoil the process. In a new study, researchers in Georgia Tech’s School of Biological Sciences have engineered one of the world’s first strains of yeast that may be happier with the lights on.
“We were frankly shocked by how simple it was to turn the yeast into phototrophs (organisms that can harness and use energy from light),” says Anthony Burnetti, a research scientist working in Associate Professor William Ratcliff’s laboratory and corresponding author of the study. “All we needed to do was move a single gene, and they grew 2% faster in the light than in the dark. Without any fine-tuning or careful coaxing, it just worked.”
Easily equipping the yeast with such an evolutionarily important trait could mean big things for our understanding of how this trait originated — and how it can be used to study things like biofuel production, evolution, and cellular aging.
The research was inspired by the group’s past work investigating the evolution of multicellular life. The group published their first report on their Multicellularity Long-Term Evolution Experiment (MuLTEE), uncovering how their single-celled model organism, “snowflake yeast,” was able to evolve multicellularity over 3,000 generations. Throughout these evolution experiments, one major limitation for multicellular evolution appeared: energy.
“Oxygen has a hard time diffusing deep into tissues, and you get tissues without the ability to get energy as a result,” says Burnetti. “I was looking for ways to get around this oxygen-based energy limitation.”
One way to give organisms an energy boost without using oxygen is through light. But the ability to turn light into usable energy can be complicated from an evolutionary standpoint. For example, the molecular machinery that allows plants to use light for energy involves a host of genes and proteins that are hard to synthesize and transfer to other organisms — both in the lab and naturally through evolution. Luckily, plants are not the only organisms that can convert light to energy.
A simpler way for organisms to use light is with rhodopsins: proteins that can convert light into energy without additional cellular machinery.
“Rhodopsins are found all over the tree of life and apparently are acquired by organisms obtaining genes from each other over evolutionary time,” says Autumn Peterson, a biology Ph.D. student working with Ratcliff and lead author of the study.
This type of genetic exchange is called horizontal gene transfer and involves sharing genetic information between organisms that aren’t closely related. Horizontal gene transfer can cause seemingly big evolutionary jumps in a short time, like how bacteria are quickly able to develop resistance to certain antibiotics. This can happen with all kinds of genetic information and is particularly common with rhodopsin proteins.
“In the process of figuring out a way to get rhodopsins into multi-celled yeast,” explains Burnetti, “we found we could learn about horizontal transfer of rhodopsins that has occurred across evolution in the past by transferring it into regular, single-celled yeast where it has never been before.”
To see if they could outfit a single-celled organism with solar-powered rhodopsin, researchers added a rhodopsin gene synthesized from a parasitic fungus to common baker’s yeast. This specific gene is coded for a form of rhodopsin that would be inserted into the cell’s vacuole, a part of the cell that, like mitochondria, can turn chemical gradients made by proteins like rhodopsin into energy. Equipped with vacuolar rhodopsin, the yeast grew roughly 2% faster when lit — a huge benefit in terms of evolution.
“Here we have a single gene, and we’re just yanking it across contexts into a lineage that’s never been a phototroph before, and it just works,” says Burnetti. “This says that it really is that easy for this kind of a system, at least sometimes, to do its job in a new organism.”
This simplicity provides key evolutionary insights and says a lot about “the ease with which rhodopsins have been able to spread across so many lineages and why that may be so,” explains Peterson, who Peterson recently received a Howard Hughes Medical Institute (HHMI) Gilliam Fellowship for her work. Carina Baskett, grant writer for Georgia Tech’s Center for Microbial Dynamics and Infection, also worked on the study.
Because vacuolar function may contribute to cellular aging, the group has also initiated collaborations to study how rhodopsins may be able to reduce aging effects in the yeast. Other researchers are already starting to use similar new, solar-powered yeast to study advancing bioproduction, which could mark big improvements for things like synthesizing biofuels. Ratcliff and his group, however, are mostly keen to explore how this added benefit could impact the single-celled yeast’s journey to a multicellular organism.
“We have this beautiful model system of simple multicellularity,” says Burnetti, referring to the long-running Multicellularity Long-Term Evolution Experiment (MuLTEE). “We want to give it phototrophy and see how it changes its evolution.”
Loss of cohesin regulator PDS5A reveals repressive role of Polycomb loops
by Daniel Bsteh, Hagar F. Moussa, Georg Michlits, Ramesh Yelagandula, Jingkui Wang, Ulrich Elling, Oliver Bell in Nature Communications
The blueprint for human life lies within the DNA in the nucleus of each of our cells. In human cells, around six and a half feet of this genetic material must be condensed to fit inside the nucleus. DNA condensation is not random. To function properly, the genetic material is highly organized into loop structures that often bring together widely separated sections of the genome critical to the regulation of gene activity. In a new paper, USC Stem Cell scientists from the laboratory of Oliver Bell address how these loops can help repress or silence gene activity, with potentially far-reaching effects on human health.
“A carefully orchestrated regulatory machinery is required to ensure every cell in the body is expressing its correct gene set to exert its dedicated function,” said the study’s first author Daniel Bsteh, who began the research at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), and completed it at the Keck School of Medicine of USC during his PhD. He is currently the Liquid Biopsy Core Manager at the USC Norris Comprehensive Cancer Center.
In the study, Bsteh and his colleagues specifically examined developmental genes that are repressed by molecules known as Polycomb Repressive Complexes 1 and 2 (PRC1 and PRC2). PRC1 and PRC2 are regulators that prevent developmental genes from becoming activated at the wrong time or in the wrong cell, which has been shown to cause changes in cellular identity, leading to developmental defects, or transformation into cancer cells.
When PRC1- and PRC2-repressed genes come together, the genome forms loops. Loops are known to play a role in activating genes, but it has been more challenging to study how loops might help repress genes. This is because of the interdependence of loops with a different type of gene repressing mechanism known as histone modifications.
Through a genetic screen conducted in mouse embryonic stem cells, the scientists identified a protein, PDS5A, that modifies loops without affecting histone modifications. This enabled Bsteh and colleagues to specifically study the effects of loops and 3D genome organization on gene silencing.
The loss of PDS5A disrupted the loops — and therefore the long-range interactions between repressed developmental genes. Further, looping genes together maintains the silent state. When PRC1- and PRC2-repressed genes are physically separated, eliminating the loops, normally silent genes become activated in aberrant ways.
“PDS5A is a subunit of a larger protein complex called cohesin, which is the master regulator of 3D genome organization,” said Bell, an assistant professor of biochemistry and molecular medicine, and stem cell biology and regenerative medicine, and a member of the USC Norris Comprehensive Cancer Center. “Cohesin mutations are known to drive several human diseases, including developmental disorders and cancer. What’s striking about our discovery is that it reveals a dependence of PRC 1 and PRC 2 activity on the precise regulation of 3D genome organization by cohesin, suggesting that ‘cohesinopathies’ may be linked to aberrant developmental gene silencing.”
Retinoic acid signaling regulates spatiotemporal specification of human green and red cones
by Sarah E. Hadyniak, Joanna F. D. Hagen, Kiara C. Eldred, Boris Brenerman, Katarzyna A. Hussey, Rajiv C. McCoy, Michael E. G. Sauria, James A. Kuchenbecker, Thomas Reh, Ian Glass, Maureen Neitz, Jay Neitz, James Taylor, Robert J. Johnston in PLOS Biology
With human retinas grown in a petri dish, researchers discovered how an offshoot of vitamin A generates the specialized cells that enable people to see millions of colors, an ability that dogs, cats, and other mammals do not possess.
“These retinal organoids allowed us for the first time to study this very human-specific trait,” said author Robert Johnston, an associate professor of biology. “It’s a huge question about what makes us human, what makes us different.”
The findings increase understanding of color blindness, age-related vision loss, and other diseases linked to photoreceptor cells. They also demonstrate how genes instruct the human retina to make specific color-sensing cells, a process scientists thought was controlled by thyroid hormones.
By tweaking the cellular properties of the organoids, the research team found that a molecule called retinoic acid determines whether a cone will specialize in sensing red or green light. Only humans with normal vision and closely related primates develop the red sensor.
Scientists for decades thought red cones formed through a coin toss mechanism where the cells haphazardly commit to sensing green or red wavelengths — and research from Johnston’s team recently hinted that the process could be controlled by thyroid hormone levels. Instead, the new research suggests red cones materialize through a specific sequence of events orchestrated by retinoic acid within the eye.
The team found that high levels of retinoic acid in early development of the organoids correlated with higher ratios of green cones. Similarly, low levels of the acid changed the retina’s genetic instructions and generated red cones later in development.
“There still might be some randomness to it, but our big finding is that you make retinoic acid early in development,” Johnston said. “This timing really matters for learning and understanding how these cone cells are made.”
Green and red cone cells are remarkably similar except for a protein called opsin, which detects light and tells the brain what colors people see. Different opsins determine whether a cone will become a green or a red sensor, though the genes of each sensor remain 96% identical. With a breakthrough technique that spotted those subtle genetic differences in the organoids, the team tracked cone ratio changes over 200 days.
“Because we can control in organoids the population of green and red cells, we can kind of push the pool to be more green or more red,” said author Sarah Hadyniak, who conducted the research as a doctoral student in Johnston’s lab and is now at Duke University. “That has implications for figuring out exactly how retinoic acid is acting on genes.”
The researchers also mapped the widely varying ratios of these cells in the retinas of 700 adults. Seeing how the green and red cone proportions changed in humans was one of the most surprising findings of the new research, Hadyniak said.
Scientists still don’t fully understand how the ratio of green and red cones can vary so greatly without affecting someone’s vision. If these types of cells determined the length of a human arm, the different ratios would produce “amazingly different” arm lengths, Johnston said.
To build understanding of diseases like macular degeneration, which causes loss of light-sensing cells near the center of the retina, the researchers are working with other Johns Hopkins labs. The goal is to deepen their understanding of how cones and other cells link to the nervous system.
“The future hope is to help people with these vision problems,” Johnston said. “It’s going to be a little while before that happens, but just knowing that we can make these different cell types is very, very promising.”
Subscribe to Paradigm!
Medium. Twitter. Telegram. Telegram Chat. Reddit. LinkedIn.
Main Sources
Research articles
