Hornwort genomes provide clues on how plants conquered the land

 

Over 450 million years ago, plants began the epic transition from water to dry land. Among the first pioneers were the ancestors of humble hornworts, a group of small, unassuming plants that have persisted to this day. New research reveals insights into the genetic blueprints of hornworts, uncovering fascinating details about plant evolution and the early days of life on land.

"We began by decoding the genomes of ten hornwort species, representing all known families within this unique plant group," said Peter Schafran, a postdoctoral scientist at the Boyce Thompson Institute (BTI) and first author of the study. "What we found was unexpected: hornworts have maintained remarkably stable chromosomes despite evolving separately for over 300 million years."

Unlike many plants, hornworts have not experienced whole-genome duplication (where an organism's entire genetic material is duplicated). This absence of duplication has resulted in stable "autosomes" -- the chromosomes that hold most of an organism's genetic material -- which have remained relatively unchanged across hornworts despite their deep evolutionary history.

However, not all parts of the hornwort genome are so static. The study revealed the presence of "accessory chromosomes" -- extra genetic material that isn't essential for survival but can provide additional benefits. These accessory chromosomes are much more dynamic, evolving rapidly and varying even within individual plants. Additionally, the international team of researchers identified potential sex chromosomes in some species, shedding light on the evolution of plant reproductive strategies.

The study, recently published in Nature Plants, also provided insights into specific plant traits. For example, the researchers uncovered new information about genes involved in flavonoid production (pigments that protect against UV radiation), stomata formation (tiny pores that regulate gas exchange), and hormone signaling. These findings help refine our understanding of how early land plants adapted to their new, challenging environment.

The research project's extensive genetic investigation of hornworts makes them the most thoroughly sequenced plant group relative to their total number of species.

By creating a comprehensive "pan-phylum" dataset for hornworts, the research team has developed a resource to help scientists comprehend how life on Earth has evolved. It provides insights into how plants might adapt to future environmental challenges and could inform efforts to engineer more resilient crops.

"Our research demonstrates the importance of studying diverse organisms, not just well-known model species," said Fay-Wei Li, associate professor at BTI and lead author. "By expanding our knowledge of hornworts, we gain a more complete picture of plant evolution and the incredible diversity of life on our planet."

Journal Reference:

1. Peter Schafran, Duncan A. Hauser, Jessica M. Nelson, Xia Xu, Lukas A. Mueller, Samarth Kulshrestha, Isabel Smalley, Sophie de Vries, Iker Irisarri, Jan de Vries, Kevin Davies, Juan Carlos A. Villarreal, Fay-Wei Li. Pan-phylum genomes of hornworts reveal conserved autosomes but dynamic accessory and sex chromosomes. Nature Plants, 2025; DOI: 10.1038/s41477-024-01883-w

Courtesy:

Boyce Thompson Institute. "Hornwort genomes provide clues on how plants conquered the land." ScienceDaily. ScienceDaily, 6 January 2025. <www.sciencedaily.com/releases/2025/01/250106132143.htm>.

 

 

 

 

Breakthrough for 'smart cell' design

 

Rice University bioengineers have developed a new construction kit for building custom sense-and-respond circuits in human cells. The research, published in the journal Science, represents a major breakthrough in the field of synthetic biology that could revolutionize therapies for complex conditions like autoimmune disease and cancer.

"Imagine tiny processors inside cells made of proteins that can 'decide' how to respond to specific signals like inflammation, tumor growth markers or blood sugar levels," said Xiaoyu Yang, a graduate student in the Systems, Synthetic and Physical Biology Ph.D. program at Rice who is the lead author on the study. "This work brings us a whole lot closer to being able to build 'smart cells' that can detect signs of disease and immediately release customizable treatments in response."

The new approach to artificial cellular circuit design relies on phosphorylation -- a natural process cells use to respond to their environment that features the addition of a phosphate group to a protein. Phosphorylation is involved in a wide range of cellular functions, including the conversion of extracellular signals into intracellular responses -- e.g., moving, secreting a substance, reacting to a pathogen or expressing a gene.

In multicellular organisms, phosphorylation-based signaling often involves a multistage, cascading effect like falling dominoes. Previous attempts at harnessing this mechanism for therapeutic purposes in human cells have focused on re-engineering native, existing signaling pathways. However, the complexity of the pathways makes them difficult to work with, so applications have remained fairly limited.

Thanks to Rice researchers' new findings, however, phosphorylation-based innovations in "smart cell" engineering could see a significant uptick in the coming years. What enabled this breakthrough was a shift in perspective:

Phosphorylation is a sequential process that unfolds as a series of interconnected cycles leading from cellular input (i.e. something the cell encounters or senses in its environment) to output (what the cell does in response). What the research team realized -- and set out to prove -- was that each cycle in a cascade can be treated as an elementary unit, and these units can be linked together in new ways to construct entirely novel pathways that link cellular inputs and outputs.

"This opens up the signaling circuit design space dramatically," said Caleb Bashor, an assistant professor of bioengineering and biosciences and corresponding author on the study. "It turns out, phosphorylation cycles are not just interconnected but interconnectable -- this is something that we were not sure could be done with this level of sophistication before.

"Our design strategy enabled us to engineer synthetic phosphorylation circuits that are not only highly tunable but that can also function in parallel with cells' own processes without impacting their viability or growth rate."

While this may sound straightforward, figuring out the rules for how to build, connect and tune the units -- including the design of intra- and extracellular outputs -- was anything but. Moreover, the fact that synthetic circuits could be built and implemented in living cells was not a given.

"We didn't necessarily expect that our synthetic signaling circuits, which are composed entirely of engineered protein parts, would perform with a similar speed and efficiency as natural signaling pathways found in human cells," Yang said. "Needless to say, we were pleasantly surprised to find that to be the case. It took a lot of effort and collaboration to pull it off."

The do-it-yourself, modular approach to cellular circuit design proved capable of reproducing an important systems-level ability of native phosphorylation cascades, namely amplifying weak input signals into macroscopic outputs. Experimental observations of this effect verified the team's quantitative modelling predictions, reinforcing the new framework's value as a foundational tool for synthetic biology.

Another distinct advantage of the new approach to sense-and-respond cellular circuit design is that phosphorylation occurs rapidly in only seconds or minutes, so the new synthetic phospho-signaling circuits could potentially be programmed to respond to physiological events that occur on a similar timescale. In contrast, many previous synthetic circuit designs were based on different molecular processes such as transcription, which can take many hours to activate.

The researchers also tested the circuits for sensitivity and ability to respond to external signals like inflammatory factors. To prove its translational potential, the team used the framework to engineer a cellular circuit that can detect these factors and could be used to control autoimmune flare-ups and reduce immunotherapy-associated toxicity.

"Our research proves that it is possible to build programmable circuits in human cells that respond to signals quickly and accurately, and it is the first report of a construction kit for engineering synthetic phosphorylation circuits," said Bashor, who also serves as deputy director for the Rice Synthetic Biology Institute, which was launched earlier this year in order to capitalize on Rice's deep expertise in the field and catalyze collaborative research.

Caroline Ajo-Franklin, who serves as institute director, said the study's findings are an example of the transformative work Rice researchers are doing in synthetic biology.

"If in the last 20 years synthetic biologists have learned how to manipulate the way bacteria gradually respond to environmental cues, the Bashor lab's work vaults us forward to a new frontier -- controlling mammalian cells' immediate response to change," said Ajo-Franklin, a professor of biosciences, bioengineering, chemical and biomolecular engineering and a Cancer Prevention and Research Institute of Texas Scholar.

 

Journal Reference:

1. Xiaoyu Yang, Jason W. Rocks, Kaiyi Jiang, Andrew J. Walters, Kshitij Rai, Jing Liu, Jason Nguyen, Scott D. Olson, Pankaj Mehta, James J. Collins, Nichole M. Daringer, Caleb J. Bashor. Engineering synthetic phosphorylation signaling networks in human cells. Science, 2025; 387 (6729): 74 DOI: 10.1126/science.adm8485 

Courtesy:

Rice University. "Breakthrough for 'smart cell' design." ScienceDaily. ScienceDaily, 3 January 2025. <www.sciencedaily.com/releases/2025/01/250103124934.htm>.

 

 

 

Virus that threatened humanity opens the future

 Professor Sangmin Lee from POSTECH's Department of Chemical Engineering, in collaboration with 2024 Nobel Chemistry Laureate Professor David Baker from the University of Washington, has developed an innovative therapeutic platform by mimicking the intricate structures of viruses using artificial intelligence (AI). Their pioneering research was published in Nature on December 18.

Viruses are uniquely designed to encapsulate genetic material within spherical protein shells, enabling them to replicate and invade host cells, often causing disease. Inspired by these complex structures, researchers have been exploring artificial proteins modeled after viruses. These "nanocages" mimic viral behavior, effectively delivering therapeutic genes to target cells. However, existing nanocages face significant challenges: their small size restricts the amount of genetic material they can carry, and their simple designs fall short of replicating the multifunctionality of natural viral proteins.

To address these limitations, the research team used AI-driven computational design. While most viruses display symmetrical structures, they also feature subtle asymmetries. Leveraging AI, the team recreated these nuanced characteristics and successfully designed nanocages in tetrahedral, octahedral, and icosahedral shapes for the first time.

The resulting nanostructures are composed of four types of artificial proteins, forming intricate architectures with six distinct protein-protein interfaces. Among these, the icosahedral structure, measuring up to 75 nanometers in diameter, stands out for its ability to hold three times more genetic material than conventional gene delivery vectors, such as adeno-associated viruses (AAV), marking a significant advancement in gene therapy.

Electron microscopy confirmed the AI-designed nanocages achieved precise symmetrical structures as intended. Functional experiments further demonstrated their ability to effectively deliver therapeutic payloads to target cells, paving the way for practical medical applications.

"Advancements in AI have opened the door to a new era where we can design and assemble artificial proteins to meet humanity's needs," said Professor Sangmin Lee. "We hope this research not only accelerates the development of gene therapies but also drives breakthroughs in next-generation vaccines and other biomedical innovations."

Professor Lee previously worked as a postdoctoral researcher in Professor Baker's laboratory at the University of Washington for nearly three years, from February 2021 to late 2023, before joining POSTECH in January 2024.

This study was supported by the Republic of Korea's Ministry of Science and ICT under the Outstanding Young Scientist Program, the Nano and Material Technology Development Program, and the Global Frontier Research Program, with additional funding provided by the Howard Hughes Medical Institute (HHMI) in the United States.

Journal Reference:

1. Sangmin Lee, Ryan D. Kibler, Green Ahn, Yang Hsia, Andrew J. Borst, Annika Philomin, Madison A. Kennedy, Buwei Huang, Barry Stoddard, David Baker. Four-component protein nanocages designed by programmed symmetry breaking. Nature, 2024; DOI: 10.1038/s41586-024-07814-1 

Courtesy:

Pohang University of Science & Technology (POSTECH). "Virus that threatened humanity opens the future." ScienceDaily. ScienceDaily, 27 December 2024. <www.sciencedaily.com/releases/2024/12/241225145516.htm>.