Why simulating an entire cell cycle took years, multiple GPUs and six days per run

 By simulating the life cycle of a minimal bacterial cell—from DNA replication to protein translation to metabolism and cell division—scientists have opened a new frontier of computer vision into the essential processes of life. The researchers, led by chemistry professor Zan Luthey-Schulten at the University of Illinois Urbana-Champaign, present undefined in the journal Cell.

The team simulated a living cell at nanoscale resolution and recapitulated how every molecule within that cell behaved over the course of a full cell cycle. The work took many years: vast computer resources, large experimental datasets, a suite of experimental and computational techniques and an understanding of the roles, behaviors and physical interactions of thousands of molecular players.

The researchers had to account for every gene, protein, RNA molecule and chemical reaction occurring within the cell to recreate the timing of cellular events. For example, their model had to accurately reflect the processes that allow the cell to double in size prior to cell division.

To make the task more manageable, the team used a living "minimal cell" developed at the J. Craig Venter Institute in California. The version of the cell used in the new study, undefined—"Syn3A" for short—is a modified bacterium with a pared-down genome that carries only the genes needed to replicate its DNA, grow, divide and perform most of the other functions that make life possible.

"This is a three-dimensional, fully dynamic kinetic model of a living minimal cell that mimics what goes on in the actual cell," Luthey-Schulten said.

"Such a comprehensive undertaking was only possible through the combined efforts of a host of collaborators at the U. of I. as well as Harvard Medical School, where we systematically modeled the essential metabolism and other subcellular networks through a series of publications starting in 2018."

Building and validating the minimal cell

The Syn3A cell has fewer than 500 genes, all of which reside on a single circular strand of DNA. The laboratories of study co-authors Angad Mehta, a professor of chemistry at the U. of I., and Taekjip Ha, of Boston Children's Hospital and Harvard Medical School, generated additional experimental data that allowed the team to accurately simulate and validate numerous aspects of cell function.

"Most importantly, their work revealed the extent of DNA replication and that Syn3A's cell division is symmetrical," Luthey-Schulten said.

Both factors guided and validated the simulations performed by Zane Thornburg, a postdoctoral fellow at the Beckman Institute for Advanced Science and Technology and the Cancer Center at Illinois, and Andrew Maytin, a graduate student in Luthey-Schulten's lab.

Like other bacterial cells, Syn3A has no nucleus. Every molecule that comprises and sustains it is either a component of its outer membrane, is transported into it from outside the cell or is assembled in the cytoplasm.

The cell is so jam-packed with molecular players that, when creating high-resolution cartoons and animations of their computer simulations, the researchers had to render some of the components invisible. Making all the cellular proteins invisible, for example, allowed the scientists to see how Syn3A's chromosome threads through the cell's crowded interior.

Some processes were more computationally expensive than others, the team discovered. For example, Maytin realized that chromosome replication was slowing the whole simulation to a crawl, nearly doubling the time it took to capture the whole cell cycle.

He determined that efficiently simulating the cell's DNA replication process required its own dedicated graphics processing unit, while another GPU handled all other cellular dynamics. This allowed the team to simulate the full, 105-minute cell cycle in just six days of computer time.

Overcoming the hurdles of 3D simulation

Thornburg and Maytin struggled with the challenge of simulating cellular events occurring at the same time in various parts of the cell.

"I can't overstate how hard it is to simulate things that are moving—and doing it in 3D for an entire cell was … triumphant," Thornburg said. "One of the last big hurdles that Andrew and I had to solve was understanding how the membrane and the DNA talk to one another when both are moving."

While the simulated cell cycle has its limitations—this was not an atom-by-atom simulation but instead averaged the dynamics of individual molecules—it yielded a surprisingly accurate accounting of the timing of cellular processes.

In repeated simulations involving individual cells with slightly varying start conditions, the simulated cell cycle occurred, on average, within two minutes of the real-world cell cycle, Thornburg said. The work was repeatedly guided and tested against actual experimental outcomes, a process that allowed the scientists to refine their simulations.

A new window into living systems

The ability to accurately capture the ever-changing conditions within a living cell opens a new window on the foundations of living systems, Luthey-Schulten said.

"We have a whole-cell model that predicts many cellular properties simultaneously," she said. "If you want to know what's going on, say, in nucleotide metabolism, you can also look at what's going on in DNA replication and the biogenesis of ribosomes. So the simulations can give you the results of hundreds of experiments simultaneously."

Study co-authors also include Illinois chemistry alumnus Benjamin Gilbert and John Glass, who leads the J. Craig Venter Institute Synthetic Biology Group.

This work was conducted at the National Science Foundation's Science and Technology Center for Quantitative Cell Biology at the U. of I. Luthey-Schulten is also a professor of physics and a professor in the Beckman Institute at the U. of I. The research was conducted using the Delta advanced computing and data resource. Delta is a joint effort of the U. of I. and its National Center for Supercomputing Applications.

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Plant mitochondria actively pull oxygen from chloroplasts, researchers discover

 A new study from the University of Helsinki reveals how plant mitochondria draw molecular oxygen away from chloroplasts, an interaction not previously documented. The discovery sheds new light on how plants regulate oxygen inside their tissues, with implications for understanding plant metabolism and stress acclimation. The research, led by Dr. Alexey Shapiguzov (Ph.D., Docent) from the University's Centre of Excellence in Tree Biology on the Viikki campus, has been undefined in Plant Physiology.

Oxygen as a central factor in plant life

Oxygen gas is central to plant metabolism, growth, stress acclimation and immunity. Recent research at the University of Helsinki has shown that undefined triggers wound healing in plants. Yet, despite its importance, scientists still lack an understanding of how oxygen levels inside plant tissues are controlled.

In plant cells, oxygen dynamics are dominated by two organelles: mitochondria that consume oxygen during respiration, and chloroplasts that produce oxygen as a by-product of photosynthesis.

While both cellular respiration and photosynthesis are well studied, the exchange of oxygen between mitochondria and chloroplasts remains largely unexplored.

Genetically modified Arabidopsis enables the study of mitochondrial functions

To investigate this gap, the research team examined undefined lines of the model plant Arabidopsis thaliana that carry mitochondrial defects. These defects switch on alternative respiratory enzymes, boosting mitochondrial oxygen consumption.

Genetically modified lines were found to carry two key features:

1. Increased mitochondrial respiration lowered oxygen levels in tissues.
2. undefined in these plants became resistant to methyl viologen, a chemical that diverts electrons from photosystem I to oxygen, producing reactive oxygen species.

Under low-oxygen conditions achieved by exposing the plants to nitrogen gas, the electron transfer to oxygen dropped dramatically. This indicated that methyl viologen was simply running out of its required substrate: oxygen.

Mitochondria 'suck out' oxygen from chloroplasts

The results suggest a previously undocumented interaction: when stressed, mitochondria can reduce oxygen levels inside chloroplasts by consuming more of it. This "oxygen drain" affects photosynthesis and metabolism of reactive oxygen species, which can help plants adjust to environmental changes.

According to Dr. Shapiguzov, to our knowledge, this is the first evidence that mitochondria influence chloroplasts through intracellular oxygen exchange. It adds a new layer to our understanding of how plants regulate energy metabolism and cope with stress.

New insights regarding plant resilience

By understanding how respiration and photosynthesis interact through oxygen exchange, scientists can better understand plant energy metabolism and responses to environmental changes such as day-night transitions or flooding. This can help develop new crop varieties.

The discovered interaction also provides new ways of measuring and imaging plant physiology, which can be helpful in breeding and in early stress detection.

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The Black Death's counterintuitive effect: As human numbers fell, so did plant diversity

Between 1347 and 1353, Europe was gripped by the most catastrophic pandemic in its history: the Black Death. Killing many millions, the plague wiped out between one-third and a half of Europe's population.

In some cities, mortality rates were as high as 80%. In rural areas, Black Death mortality caused intense labor shortages. Entire villages were left empty as rural economies collapsed. In many places, cultivated fields were abandoned and reclaimed by woodland, scrub and deer.

Given the widely reported negative effects that people have had on nature over recent decades and centuries, we might expect this continental-scale "rewilding" to have enabled biodiversity to flourish. However, our new study in the journal Ecology Letters uncovers a potentially counterintuitive result: when Europe's human population crashed, plant biodiversity also plummeted.

Fossilized pollen grains in sediment cores extracted from lakes and bogs contain information about plant communities that existed thousands of years ago. We used data from over 100 fossil pollen records from across Europe to explore how plant diversity changed before, during and after the Black Death.

The pollen data show that between 0BC and 1300, plant diversity in Europe increased. It grew through the rise and fall of the Western Roman Empire and continued through the early Middle Ages. By the High Middle Ages, biodiversity levels were at their peak.

However, in 1348, Europe was hit by plague and for about 150 years, plant biodiversity plummeted. It was only after a century and a half—as human populations recovered and farming resumed—that plant diversity began to rise again.

We found that the biggest losses of plant diversity occurred in areas most affected by land abandonment. By plotting patterns of biodiversity changes from sites with different Black Death land use histories, we discovered that biodiversity collapsed in landscapes where crop (arable) production was abandoned, whereas landscapes with growing or stable arable farming became more biodiverse.

Our work suggests that over 2,000 years of increasing European biodiversity was generated because of—not in spite of—humans. But why? And what lessons can we learn from this for managing biodiversity now, when land being converted into farmland is driving biodiversity losses?

Population growth and technological innovations pushed agricultural activities into previously unused lands over the first 1,300 years of the common era. Unlike today—where crop monocultures are dominant—mixed agricultural systems were the norm over the majority of the last 2,000 years. Across Europe, a diverse lattice of farmlands and farming practices were typically separated by woods, rough grazing lands and uncultivated plots, often enclosed by hedgerows or trees.

The result was a patchy landscape where there were lots of opportunities for different plant species to survive, and biodiversity was high.

The Black Death disrupted this by reducing human disturbance. The result was a less patchy landscape and an overall loss in plant diversity. Diversity only recovered when extensive farming returned.

People can boost nature

These findings call into question conservation policies that advocate for removing or reducing human influence from Europe's landscapes to protect biodiversity.

One such policy initiative is rewilding, which is seen by many as a route to achieving a biodiverse future where nature is given space to flourish. Yet, many of the most biodiverse locations in Europe are those with a long history of low-intensity, mixed agriculture. To rewild these human-formed landscapes may, paradoxically, risk eroding the biodiversity that conservationists seek to protect.

Our findings of long-term positive human–biodiversity relationships is not solely a European phenomenon. Multimillennial interactions between humans and the natural world have resulted in elevated biodiversity levels across the planet. Examples of diverse, cultural ecosystems include the forest gardens of the Pacific North West (forests cultivated by Indigenous peoples), the satoyama of Japan (low-intensity mixed systems of rice paddies and woodlands in mountainous foothills) and the ahupua'a of Hawaii (segments of diverse hillsides used to cultivate multiple crops).

Modern, intensive farming practices have caused substantial biodiversity losses across the globe. Yet, our Black Death findings, in combination with numerous other examples, show us that humans and nature do not always have to be kept separate to conserve and promote biodiversity. Indeed, recognizing landscapes as cultural ecosystems may help us imagine futures where both nature and people can live together and thrive.

Traditional, low-intensity land management practices have generated diverse ecosystems for millennia. Today, where locally appropriate, they should be encouraged for the conservation of both biological and cultural diversity.

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Single-Injection Immunotherapy That Halts Alzheimer’s

 The growth form of giant kelp (Macrocystis pyrifera) is composed of shoots known as stipes instead of branches. From one parent holding fast to the hard bottom might come as many as 150 stipes. Typically, the tips of the biggest kelp bob at the ocean surface and calm the waters, appearing as patches of gold visible from land—a sign of the good health of the ecosystem that it anchors. But the kelp, as San Diego knows it, is in trouble.

A team led by UC San Diego's Scripps Institution of Oceanography released an unmatched history of kelp forests off La Jolla and Point Loma. Together spanning nearly 19 square kilometers (7.3 square miles), they are the largest on the United States West Coast. Amassed over more than 40 years, their story reveals a progression of steady decline that transcends typical cycles of crash and recovery. The findings are published in the journal Ecological Applications.

Now, say the researchers, competing organisms usually cast in shadow by the kelp are emerging as winners. The giant kelp are losing, but so might be myriad other organisms—fishes and humans included—as another natural order is disrupted by climate change and other new circumstances.

The downsides range from a decrease in the catch available to recreational fishers in San Diego to the loss of the nurseries that sea stars and open ocean fishes use to protect their larvae. Even the beach wrack—the large piles of decaying kelp that wash up after storms—is diminishing. Though the absence of the pungent kelp will be a relief to some beachgoers, those piles attract the kelp flies that are an important source of food for seabirds.

"It's like starving the system," said study lead author Ed Parnell, a marine biologist at Scripps Oceanography. "Giant kelp is an iconic species. It's highly productive. It provides a lot of food for animals. It's better for beaches. There are rafts of kelp paddies that pelagic fish use to protect their eggs."The Scripps Oceanography study tracks the story of more than 14,000 giant kelp plants over the course of decades. Some of the data gathered dates to the 1970s, when veteran study co-authors were early in their careers. The bulk of the story, though, starts in 1983 when Scripps marine biologists Paul Dayton and the late Mia Tegner created the first of 20 stations to follow how kelp grew at various depths and in conditions ranging from rough open ocean-facing waters to relatively tranquil patches. Each station has four permanent transects 25 meters (82 feet) long situated perpendicular to the coast.

"It's kind of mind boggling to think of how much data we collected," said Kristin Riser, a study co-author and a staff research associate who started at Scripps in 1990. "It's probably the longest time series like this in existence and it's unique in that we followed individual plants."

The plight of giant kelp elsewhere along the West Coast has garnered enough attention to elicit Congressional action. Legislators have pushed the "Help our Kelp" Act since 2023. The bill seeks to establish a NOAA grant to support conservation and management of American kelp forests.

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A new face for 'Little Foot,' the most complete Australopithecus skeleton to date

 What did the face of our ancestors look like three million years ago? Our international team has answered this question by virtually reconstructing the facial fragments of Little Foot, the most complete Australopithecus skeleton yet discovered. This reconstruction sheds light on the influence of the environment on how our face evolved. Our findings have just been published in the Comptes Rendus Palevol journal, and the new 3D face of Little Foot can be explored online on the MorphoSource platform.

The search for human origins has never been more fruitful, with fossil discoveries pushing back the appearance of the earliest humans (members of the genus Homo) to 2.8 million years ago, and the development of cutting-edge methods for analyzing these remains, such as recovering genetic information from fossils over two million years old.

Yet, while our knowledge of extinct human species grows with each discovery, the story of our ancestors before the first humans appeared remains blurry. It is during this pivotal period that the traits defining our humanity emerged, enabling our genus' evolutionary success.

Although the identity of our direct pre-Homo ancestor is far from resolved, one fossil group plays a central role in this search: Australopithecus. This genus, to which the famous "Lucy" belongs (discovered 50 years ago in Ethiopia), inhabited much of Africa and survived for over two million years. Australopithecus is known from many fossil remains, but often these are highly fragmentary, isolated, and have sometimes been distorted over the millions of years they have been buried. Notably, only a handful of skulls preserve nearly the entire face, a part of our anatomy that has profoundly shaped who we are today.

Through digestive, visual, respiratory, olfactory and non-verbal communication systems, the face is at the heart of interactions between individuals and their physical and social environments.

Significant changes occurred in the facial region throughout human evolution, with most structures generally becoming less robust. However, the factors driving these changes remain unclear. Were they caused by shifts in diet, social behavior, or both? Only the discovery of more complete skulls can clarify this debate, and this is why the skull of Little Foot is crucial.

The 'Cradle of Humankind'

South Africa has been and remains a crucial region for research into human origins. A century ago, the iconic "Taung Child" was published in Nature as a representative of a new African branch of humanity, Australopithecus. While scientific attention had previously focused on Eurasia, this discovery inspired decades of exploration and major finds across Africa.

In particular, South Africa saw a proliferation of paleontological sites in a region now UNESCO-listed and known as the "Cradle of Humankind." Among these, Sterkfontein has proven exceptionally rich in fossils, many attributed to the hominin genus Australopithecus, and including numerous remarkably preserved specimens.

But it was in 1994 and 1997 that Sterkfontein yielded its most spectacular find: the skeleton of Little Foot, over 90% complete, and the oldest human ancestor found in southern Africa. To date, it is the most complete Australopithecus skeleton ever discovered, far surpassing Lucy, of which only 40% of the anatomy is preserved.

Our team has been studying this skeleton since its complete excavation concluded in 2017. The skull, in particular, has been the focus of our attention, as it is relatively complete, preserving all parts of the head—the cranium and mandible. However, 3.7 million years of burial underground have fragmented and displaced parts of its fossilized face. This process is especially visible in the forehead and eye sockets (orbits), making it impossible to quantitatively analyze these informative areas. Given the exceptional and unique nature of this fossil, we decided to harness the most recent technological advances in imaging to restore the face of Little Foot.

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How an underground fungal map of the world's oldest, slowest-growing rainforest trees can boost Earth's resilience

The temperate rainforests of the Chilean Coast Range are home to a spectacular array of life: iridescent blue lizards, tiny wild cats called kodkods, and curly vines of waxy red bellflowers. Towering over this biodiversity are endangered ancient conifers, called alerce (Fitzroya cupressoides), whose trunks can get as wide as shipping containers. These alerce forests show exceptionally low mortality and grow slowly—one tree lived more than 3,600 years.

Ancient giants and hidden fungal worlds

New research published today in the journal Biodiversity and Conservation makes clear that these massive trees also shelter an enormous assortment of organisms belowground that have helped the forest, a massive carbon sink, survive and adapt over millennia.

One large individual—estimated to be over 2,400 years old—hosts more than twice the underground fungal diversity of smaller, younger trees of the same species. The bigger the alerce, the greater the variety of fungi that scientists found hidden in the soil, including hundreds of species that are likely new to science.

The discovery is important because these soil fungi, known as mycorrhizal fungi, help forests function. They funnel water and nutrients to trees through their root systems and assist plants in fighting stressors like drought and pathogens. The fungi also work as conduits for drawing carbon into soil. Globally, arbuscular mycorrhizal fungal communities—the type associated with alerce trees—move roughly one billion tons of carbon per year into Earth's soils.

The scientists determined that protecting and conserving old trees will protect hundreds, if not thousands, of mycorrhizal and other fungal species that inhabit soils around these giants, each of which play a role we might not fully understand in keeping these forests healthy and resilient.

"Not all trees are the same and if you remove a millennial tree, the impact on all the other species is going to be bigger than if you remove a smaller one," said the study's co-lead author Dr. Camille Truong, a research scientist with the Royal Botanic Gardens Victoria and the University of Melbourne in Australia, and a mycorrhizal ecologist at the Society for the Protection of Underground Networks (SPUN).

Taking out one huge tree, in other words, can destroy an entire underground community of forest helpers that took thousands of years to assemble.

And "all that diversity means resilience," said Truong's co-lead author Dr. Adriana Corrales, Field Science Lead at SPUN.

The study grew out of an expedition to Alerce Costero National Park in Chile in 2022 by scientists with Universidad Santo Tomás, Universidad Austral de Chile, Universidad de La Frontera (Chile), Fungi Foundation and SPUN, a non-profit dedicated to mapping and conserving mycorrhizal fungal networks across the planet. SPUN was co-founded by evolutionary biologist Dr. Toby Kiers. Kiers was recently awarded the Tyler Prize (often called the "Nobel for the Environment") for her work detailing the importance of underground fungal networks in unique ecosystems all over the world.

Alerce, sometimes called Patagonian cypress trees or lawal in Mapudungun, the language of the local Indigenous Mapuche people, are the second-longest-lived tree species on Earth after bristlecone pines. They are cousins to North America's redwoods but live even longer. Alerce forests are found along the coasts of southern Chile and in the foothills of the Andes, but their range shrunk roughly in half over centuries as trees were cut for their durable light-weight wood or burned to make way for pasture. In fact, the oldest known individual, which lived 3,622 years, was regrettably felled in 1976.

And the trees are still threatened by land-use shifts, climate change, and major infrastructure projects. One proposed road would run just a few hundred meters from alerce forests, increasing the threat of fires, tourist pressure, and invasive species.

So, wanting to understand what was at risk and how best to protect remaining stands, Kiers and other researchers took soil samples from below 31 individual trees, ranging from saplings to the "Alerce Abuelo," which is at least 2,400 years old, with a trunk that stretches more than 4.5 meters in diameter. They measured the size and biomass of each tree, later extracted DNA from the samples, and used genetic markers to identify fungi.

Truong then analyzed the soil data alongside the tree measurements and found that the fungal diversity in ground below the largest, oldest specimen was more than 2.25 times higher than in any other sample. Those soil samples also included more than 300 species of fungi unique to this tree.

This matters because losing soil fungal diversity "can trigger cascading, negative effects on multiple ecosystem functions," the researchers wrote in their paper. These huge millennial trees serve as an "umbrella" that protects soil fungal diversity. Protecting that diversity can help keep other plants in the forest healthy.

Their paper is titled "Large-diameter trees disproportionately contribute to soil fungal diversity in a coniferous forest with one of oldest living trees on Earth."

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Large land predators were hunting big plant-eaters more than 280 million years ago, study finds

 A study examining fossil evidence shows that large land predators were already hunting big plant-eating animals more than 280 million years ago. University of Toronto Mississauga researchers Jordan M. Young, Tea Maho, and Robert Reisz studied bite marks on the skeletons of three young herbivores from the early Permian of Texas, revealing feeding patterns from multiple predators and a glimpse into how animals hunted and interacted with each other.

"This discovery shows predator-prey hierarchies were formed earlier than previously expected," said Professor Reisz, co-author of the work titled "Earliest direct evidence of trophic interactions between terrestrial apex predators and large herbivores."

"While these interactions are well known in the 'Age of Reptiles,' there has been little information available in the Paleozoic Era, when terrestrial vertebrates first evolved into large apex predators and herbivores," added Reisz.

Master's student Young, lead author of the study published in the journal Scientific Reports, highlights how the size, shape, and texturing of the tooth markings reveals who the potential predators are during this time period.

"The puncturing, pitting, scoring and furrowing marks on the skeletons of these three young plant-eating animals are indicative of large predators found on this site and in nearby areas, including varanopid (Varanops) and sphenacodontid (Dimetrodon) synapsids," said Young.

He added that scavengers and small arthropods also joined in on the Paleozoic feast. The skeletons showed arthropod borings on areas where cartilaginous bone ends would be on the carcass.

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