TL;DR
- Plant signaling pathways decoded
- Day/night cycles: moths may use ‘disco gene’
- Newly discovered gene may influence longevity
- How cells use condensation to seal tissues tight
- Blood stem cell breakthrough could transform bone marrow transplants
Overview
Genetic technology is defined as the term that 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
According to Global Genetic Engineering Market Research Report: The genetic engineering market is projected to grow from USD 1.36 Billion in 2023 to USD 7.73 Billion by 2032, exhibiting a compound annual growth rate (CAGR) of 24.20% during the forecast period (2023–2032).
Growing demand for synthetic genes and increased use of CRISPR genome editing technology across various biotechnology industries are the key market drivers enhancing the market growth. In addition, it’s projected that increased government financing, a rise in the output of genetically modified crops, and an increase in genomics studies will all contribute to the expansion.
Latest Research
Probing plant signal processing optogenetically by two channelrhodopsins
by Meiqi Ding, Yang Zhou, Dirk Becker, Shang Yang, Markus Krischke, Sönke Scherzer, Jing Yu-Strzelczyk, Martin J. Mueller, Rainer Hedrich, Georg Nagel, Shiqiang Gao, Kai R. Konrad in Nature
When it comes to survival, plants have a huge disadvantage compared to many other living organisms: they cannot simply change their location if predators or pathogens attack them or the environmental conditions change to their disadvantage.
For this reason, plants have developed different strategies with which they react to such attacks. Such reactions are usually triggered by certain signals from the environment. As has long been known, the intracellular calcium concentration plays an important role in the processing of these signals.
However, in addition to changes in the cytoplasmic calcium level, changes in the cell’s membrane potential have also been suspected as a signal transmitter. Research groups from the Departments of Neurophysiology, Pharmaceutical Biology and Botany at Julius-Maximilians-Universität Würzburg (JMU) have investigated the calcium-membrane potential relationship in more detail. They have now published their findings in the journal Nature.
For their study, the research teams worked with tobacco plants that carry ion channels that can be specifically switched on with light. More than 20 years ago, Peter Hegemann, Georg Nagel and Ernst Bamberg initiated the success of optogenetics, with their discovery and characterization of light-activated ion channels, so-called channelrhodopsins. With the help of these light-sensitive proteins, which are obtained from algae and microorganisms, the JMU researchers were able to experimentally investigate whether the influx of calcium ions or anion efflux-mediated depolarization of the cell membrane is decisive for the plant’s reaction to a certain stress situation. However, the scientists had to do a great deal of preparatory work before they were able to do this.
Channelrhodopsins, ion channels that carry an intrinsic rhodopsin-based light switch, revolutionized neuroscience through the light-controlled investigation of neuronal networks. The use of channelrhodopsins in plant research only became possible 20 years later, through close collaboration between the group of Georg Nagel, Professor at the Institute of Physiology at JMU, and plant researchers from the Würzburg Chairs of Botany 1, 2 and Pharmaceutical Biology.
In 2021, Georg Nagel’s group, together with Dr. Kai Konrad, group leader at the JMU Chair of Prof. Rainer Hedrich Botany 1, published an approach to optimize the use of channelrhodopsins in plants by overcoming three main difficulties.
Point 1: “Like all rhodopsins, including those in our eyes, channelrhodopsins require the small molecule retinal, also known as vitamin A, to absorb light. We humans get retinal mainly from beta-carotene, the provitamin A. However, land plants do not contain retinal, but a lot of beta-carotene,” explains Dr. Shiqiang Gao, co-author of the Nature publication and ‘rhodopsin engineer’ from the Optogenetics lab of the Department of Neurophysiology at JMU.
In 2021, Gao succeeded for the first time in combining the expression of channelrhodopsins with the production of retinal from beta-carotene in plant cells. This enabled the development of tobacco plants with a high retinal content and successful expression of channelrhodopsins.
Dr. Markus Krischke from the Metabolomics Core Unit at the Department of Pharmaceutical Biology headed by Professor Martin Müller at JMU Würzburg confirmed the high retinal content of the various transgenic tobacco plants.
Comparable transgenic tobacco plants were produced for the recently published study by Dr. Meiqi Ding from the Department of Botany I under the direction of plant physiologist and expert for plant signal processing Dr. Kai Konrad from the group of Professor Rainer Hedrich at the Department of Botany I.
Point 2: “Most rhodopsins are activated by blue or green light. However, this is always a component of white light,” explains Georg Nagel. As a result, the tobacco plants could not be grown in a greenhouse or under artificial white light, as is usually the case. Only in special growth chambers with red LED light, which can be used photosynthetically, it was possible to avoid unwanted rhodopsin activation. Tests under different growth conditions showed: “Tobacco develops healthily and unchanged under red light compared to greenhouse conditions,” says Dr. Kai Konrad.
Point 3: The expression of chanelrhodopsin in tobacco cells often causes difficulties. In 2021, the Würzburg team of scientists succeeded in expressing the light-activated anion channel GtACR1 in tobacco plant cells. As a result, Georg Nagel’s team was able to develop various channelrhodopsins that were optimized for the permeability of calcium ions. Finally, Dr. Shiqiang Gao and Dr. Shang Yang, both members of Nagel’s group, succeeded in developing a very good calcium-conducting channelrhodopsin XXM 2.0 for targeted expression in tobacco plants.
This was the breakthrough: “The successful expression of channelrhodopsins with different ion selectivity in plant cells enables the comparison of different ion signals in parallel to the electrical signal, the so-called depolarization,” explains Dr. Meiqi Ding. She used the calcium-conducting channelrhodopsin XXM 2.0 and the light-activated anion channel GtACR1 to investigate the different ion signaling pathways in tobacco.
These newly generated “optogenetic” tobacco plants made it possible to clarify the question of whether calcium influx or membrane depolarization is decisive for the plant’s response to a specific stress situation. “The answer was clear,” says Dr. Kai Konrad, corresponding author. First author Dr. Meiqi Ding from Dr. Konrad’s group explains, “After activation of the anion channel, the leaves wilted and responded with the typical plant response to drought; the plant hormone abscisic acid (ABA) was produced and gene expression was ramped up to protect against desiccation.”
“However, in the plants with the calcium channel, there was no change in ABA levels after optogenetic stimulation,” Dr. Ding continued. “Instead, the plants produced signal molecules and plant hormones to initiate defence mechanisms against predators, recognizable by white spots on the leaves,” said Dr. Konrad.
Dr Sönke Scherzer at the chair of Prof Hedrich was able to show by direct ROS measurements that reactive oxygen species (ROS) are released in the process.
Dirk Becker and Rainer Hedrich at the Chair of Botany 1, designed an experimental approach to support the working hypothesis using transcriptomic and bioinformatic analysis.
The scientists are convinced that this study is just the beginning of a new era in plant research. Ultimately, the signaling pathways of plants can now be better “illuminated” using various rhodopsins.
Day–night gene expression reveals circadian gene disco as a candidate for diel-niche evolution in moths
by Yash Sondhi, Rebeccah L. Messcher, Anthony J. Bellantuono, Caroline G. Storer, Scott D. Cinel, R. Keating Godfrey, Andrew J. Mongue, Yi-Ming Weng, Deborah Glass, Ryan A. St Laurent, Chris A. Hamilton, Chandra Earl, Colin J. Brislawn, Ian J. Kitching, Seth M. Bybee, Jamie C. Theobald, Akito Y. Kawahara in Proceedings of the Royal Society B: Biological Sciences
How does one species become two? If you’re a biologist, that’s a loaded question. The consensus is that, in most cases, the process of speciation occurs when individuals from a single population become geographically isolated. If they remain separate long enough, they lose the ability to interbreed.
A new study demonstrates what happens when a less common form of speciation occurs. Rather than being separated by a physical barrier, such as a mountain range or an ocean, members of a species can become separated in time. The researchers focused on two closely related moth species with overlapping ranges in the southeastern United States.
“These two are very similar,” said lead author Yash Sondhi, who conducted research for the study while working at Florida International University and later at the Florida Museum of Natural History. “They’ve differentiated along this one axis, which is when they fly.”
Rosy maple moths, in the genus Dryocampa, look like what you’d get if Roald Dahl painted something from a fever dream. They bear a thick lion’s mane above their head and abdomen, and their vibrant scales are the color of strawberry and banana taffy. Both male and female rosy moths fly exclusively at night.
Pink-striped oakworm moths, in the genus Anisota, are less flashy, with subtle grades of ochre, umber and marl. While females of this species are active at dusk and early evening, the males prefer to fly during the day.
Sondhi knew from previous research that these two groups, Dryocampa and Anisota, originated from a single species approximately 3.8 million years ago, which is relatively recent on evolutionary time scales. There’s a handful of species in the genus Anisota, all of which are active during the day. The nocturnal rosy maple moths are the only species in the genus Dryocampa.
Sondhi specializes in the biology of insect vision and saw the moth pair as the perfect opportunity to explore how vision evolves when a species switches up its pattern of activity. But things didn’t go as planned.
“I went in looking for differences in color vision. Instead, we found differences in their clock genes, which in hindsight makes sense,” Sondhi said.
Clock genes control the circadian rhythm of plants and animals. The ebb and flow of the proteins they create causes cells to become either active or dormant over a period of roughly 24 hours. They affect everything from metabolism and cell growth to blood pressure and body temperature.
For any organism reversing its pattern of activity, clock genes are virtually guaranteed to be involved. “It’s a system that’s been retained in everything from fruit flies to mammals and plants. They all have some kind of time-keeping mechanism,” he said.
Sondhi compared the transcriptomes of the two moths. Unlike genomes, which contain the entirety of an organism’s DNA, transcriptomes contain only the subset of genetic material that is being actively used to make proteins. This makes them useful for exploring differences in protein levels throughout the day.
As expected, Sondhi found a number of genes that were expressed in different quantities in the two moth species. Nocturnal rosy maple moths invested more energy in their sense of smell, whereas the day-flying oakworm moth produced more genes associated with vision.
There were, however, no differences in the genes that confer the ability to see color. That doesn’t necessarily mean that their color vision is identical, but if differences do exist, they are likely at the level of tuning and sensitivity and not in the structure of the genes themselves.
There was an additional gene that stood out. Disconnected, or disco, was expressed at different levels during the day and night in both species. In fruit flies, disco is known to indirectly influence circadian rhythms through the production of neurons that transmit clock enzymes from the brain to the body.
The disco gene Sondhi found in his moth samples was twice the size of its fruit fly counterpart, and it had additional zinc fingers — active portions of a gene that directly interacts with DNA, RNA and proteins. It seemed likely that changes in the disco gene were at least partially responsible for the switch to night-flying in rosy maple moths.
When he compared the disco gene of rosy maple moths with the one in oakworms, he found 23 mutations that made each distinct from the other. The mutations were also located in active portions of the gene, meaning they likely contribute to observable physical differences between the moths. Sondhi was looking at evolution in action.
“If this is functionally confirmed, this is a really concrete example of the mechanism behind how they speciated at the molecular level, which is rare to come by,” he said.
The study is also an important push for a better understanding of the various ways in which life sustains and propagates itself. When genetics first became a field of study, researchers focused most their efforts on a few representative species, such as fruit flies or lab mice. This was done primarily for the sake of expediency, but it limits how much we know about broad biological patterns. Just as a human is not a lab mouse, a moth is not a fruit fly.
“As species continue to decline due to climate change and other anthropogenic changes, we’ll need to genetically engineer a greater number of the ones that remain to enable drought tolerance, for example, or to be active in light polluted regimes. To do that consistently, having a broader pool of functionally characterized genes across organisms is crucial. We can’t just use Drosophila,” Sondhi said.
FOXO-regulated OSER1 reduces oxidative stress and extends lifespan in multiple species
by Jiangbo Song, Zhiquan Li, Lei Zhou, Xin Chen, Wei Qi Guinevere Sew, Héctor Herranz, Zilu Ye, Jesper Velgaard Olsen, Yuan Li, Marianne Nygaard, Kaare Christensen, Xiaoling Tong, Vilhelm A. Bohr, Lene Juel Rasmussen, Fangyin Dai in Nature Communications
Sleep, fasting, exercise, green porridge, black coffee, a healthy social life …There is an abundance of advice out there on how to live a good, long life. Researchers are working hard to determine why some people live longer than others, and how we get the most out of our increasingly long lives.
Now researchers from the Center for Healthy Aging, Department of Cellular and Molecular Medicine at the University of Copenhagen have made a breakthrough. They have discovered that a particular protein known as OSER1 has a great influence on longevity.
“We identified this protein that can extend longevity (long duration of life, red.). It is a novel pro-longevity factor, and it is a protein that exists in various animals, such as fruit flies, nematodes, silkworms, and in humans,” says Professor Lene Juel Rasmussen, senior author behind the new study.
Because the protein is present in various animals, the researchers conclude that new results also apply to humans:
“We identified a protein commonly present in different animal models and humans. We screened the proteins and linked the data from the animals to the human cohort also used in the study. This allows us to understand whether it is translatable into humans or not,” says Zhiquan Li, who is a first author behind the new study and adds:
“If the gene only exists in animal models, it can be hard to translate to human health, which is why we, in the beginning, screened the potential longevity proteins that exist in many organisms, including humans. Because at the end of the day we are interested in identifying human longevity genes for possible interventions and drug discoveries.”
The researchers discovered OSER1 when they studied a larger group of proteins regulated by the major transcription factor FOXO, known as a longevity regulatory hub.
“We found 10 genes that, when — we manipulated their expression — longevity changed. We decided to focus on one of these genes that affected longevity most, called the OSER1 gene,” says Zhiquan Li.
When a gene is associated with shorter a life span, the risk of premature aging and age-associated diseases increases. Therefore, knowledge of how OSER1 functions in the cells and preclinical animal models is vital to our overall knowledge of human aging and human health in general.
“We are currently focused on uncovering the role of OSER1 in humans, but the lack of existing literature presents a challenge, as very little has been published on this topic to date. This study is the first to demonstrate that OSER1 is a significant regulator of aging and longevity. In the future, we hope to provide insights into the specific age-related diseases and aging processes that OSER1 influences,” says Zhiquan Li.
The researchers also hope that the identification and characterization of OSER1 will provide new drug targets for age-related diseases such as metabolic diseases, cardiovascular and neuro degenerative diseases.
“Thus, the discovery of this new pro-longevity factor allows us to understand longevity in humans better,” says Zhiquan Li.
Membrane prewetting by condensates promotes tight-junction belt formation
by Karina Pombo-García, Omar Adame-Arana, Cecilie Martin-Lemaitre, Frank Jülicher, Alf Honigmann in Nature
Our bodies and organs are shielded from the external environment by tissue barriers like the skin. These barriers must be tightly sealed to prevent unwanted substances from entering. This sealing is achieved through structures called tight junctions. However, how these tight junctions form has long been a mystery. Now, an interdisciplinary team of researchers, led by Prof. Alf Honigmann at the Biotechnology Center (BIOTEC) of Dresden University of Technology, has uncovered that the proteins responsible for these seals form a liquid-like material on the cell surface much like the water that condenses on a cold window.
Our skin acts as a protective shield against the outside world, and like a well-built brick wall, it must be tightly sealed to prevent breaches. Similarly, our organs like lungs or intestines must be sealed to make sure that the contents are not spilling to other body compartments. The outermost layer of our organs achieves this with specialized seals between the cells known as tight junctions.
Tight junctions are much like a joint between floor or wall tiles. They are belts that surround the top of each cell and attach to the neighboring cells to form a tight seal between them.
“Unlike the joint between the tiles or mortar in the brick wall, tight junctions are dynamic. Our skin or organs are soft and the cells change their shape constantly. Tight junctions must be able to adapt to cell shape change and still be able to seal the gaps,” explains Prof. Honigmann, chair of Biophysics and research group leader at the BIOTEC. “How tight junctions are able to form such a robust yet flexible material around the cell perimeter was an intriguing scientific question.”
To understand how these seals form, Prof. Honigmann’s team used advanced biophysical methods to observe the process in real-time. They developed a way to chemically switch the formation of tight junctions on and off at their will. They also used genetic engineering to tag the sealing proteins with a fluorescent marker. Together, this allowed them to use high-resolution microscopy to watch tight junctions form in real-time.
Working together with theoretical physicists led by Frank Jülicher at the Max Planck Institute for Physics of Complex Systems (MPI-PKS) in Dresden, the group was able to show that tight junction self-assembly is driven by a physical phenomenon called surface wetting.
“It is fascinating that these tight junction proteins behave in a very similar way to water. Putting together our observations and the theoretical physics modeling, we arrived at what is essentially the physical process of liquid condensation on a surface,” says Dr. Karina Pombo-Garcia, the researcher behind the project and now a research group leader at the Rosalind Franklin Institute in England.
Tight junction proteins bind to the surface of the cell membrane at the interface where the cells touch each other. When the number of proteins bound there reaches a certain threshold, the proteins condense into a liquid that gradually grows into a sort of drop on the cell surface. Eventually, these drops elongate and touch each other to form a uniform belt around the cells. In this way, tight junctions seal the spaces between the cells to make our skin and organs airtight.
“Perhaps everybody has seen it in winter. Tiny drops of water appear on a cold window. It’s exactly that but on a molecular scale,” adds Dr. Pombo-Garcia.
As early as 2017, the Honigmann team began to suspect that tight junction proteins might behave like liquids. “We put a lot of effort into figuring out how to measure and observe these liquid-like properties,” says Prof. Honigmann. “Fortunately, we were in the right place at the right time.”
The early work leading to this discovery was conducted at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden. Researchers at the MPI-CBG are pioneers of condensate biology, the newly discovered branch of biology that focuses on proteins forming large assemblies with liquid-like properties.
“Condensate biology is a promising field, because it bridges the gap between scales. One of the general problems in biology is to understand how structures like cell organelles form from the myriads of molecular interactions in the cytoplasm. We know now that certain biomolecules can self-organize into materials such as liquids and gels. This enables us to adapt well-understood physical concepts such as condensation and other phase transitions to describe structure formation in biology,” concludes Prof. Honigmann.
Long-term engrafting multilineage hematopoietic cells differentiated from human induced pluripotent stem cells
by Elizabeth S. Ng, Gulcan Sarila, Jacky Y. Li, Hasindu S. Edirisinghe, Ritika Saxena, Shicheng Sun, Freya F. Bruveris, Tanya Labonne, Nerida Sleebs, Alexander Maytum, Raymond Y. Yow, Chantelle Inguanti, Ali Motazedian, Vincenzo Calvanese, Sandra Capellera-Garcia, Feiyang Ma, Hieu T. Nim, Mirana Ramialison, Constanze Bonifer, Hanna K. A. Mikkola, Edouard G. Stanley, Andrew G. Elefanty in Nature Biotechnology
Melbourne researchers have made a world first breakthrough into creating blood stem cells that closely resemble those in the human body. And the discovery could soon lead to personalised treatments for children with leukaemia and bone marrow failure disorders.
The research, led by Murdoch Children’s Research Institute (MCRI) a, has overcome a major hurdle for producing human blood stem cells, which can create red cells, white blood cells and platelets, that closely match those in the human embryo.
MCRI Associate Professor Elizabeth Ng said the team had made a significant discovery in human blood stem cell development, paving the way for these lab grown cells to be used in blood stem cell and bone marrow transplants.
“The ability to take any cell from a patient, reprogram it into a stem cell and then turn these into specifically matched blood cells for transplantation will have a massive impact on these vulnerable patients’ lives,” she said.
“Prior to this study, developing human blood stem cells in the lab that were capable of being transplanted into an animal model of bone marrow failure to make healthy blood cells had not been achievable. We have developed a workflow that has created transplantable blood stem cells that closely mirror those in the human embryo. “Importantly, these human cells can be created at the scale and purity required for clinical use.”
In the study, immune deficient mice were injected with the lab engineered human blood stem cells. It found the blood stem cells became functional bone marrow at similar levels to that seen in umbilical cord blood cell transplants, a proven benchmark of success.
The research also found the lab grown stem cells could be frozen prior to being successfully transplanted into the mice. This mimicked the preservation process of donor blood stem cells before being transplanted into patients.
MCRI Professor Ed Stanley said the findings could lead to new treatment options for a range of blood disorders.
“Red blood cells are vital for oxygen transport and white blood cells are our immune defence, while platelets cause clotting to stop us bleeding,” he said. Understanding how these cells develop and function is like decoding a complex puzzle.
“By perfecting stem cell methods that mimic the development of the normal blood stem cells found in our bodies we can understand and develop personalised treatments for a range of blood diseases, including leukaemias and bone marrow failure.”
MCRI Professor Andrew Elefanty said while a blood stem cell transplant was often a key part of lifesaving treatment for childhood blood disorders, not all children found an ideally matched donor.
“Mismatched donor immune cells from the transplant can attack the recipient’s own tissues, leading to severe illness or death,” he said. “Developing personalised, patient-specific blood stem cells will prevent these complications, address donor shortages and, alongside genome editing, help correct underlying causes of blood diseases.”
Professor Elefanty said the next stage, likely in about five years with government funding, would be conducting a phase one clinical trial to test the safety of using these lab-grown blood cells in humans.
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