Scientists from Ataturk University use gene editing to increase the growth of rainbow trout. Injecting two guide RNAs targeting the first exon of the myostatin gene mstnb1 into fertilized rainbow trout eggs, the team was able to increase the trouts’ body weight by 56%. The results suggest that CRISPR–Cas9 could help shorten production time and improve production efficiency in aquaculture.
Seoul-based pharma DuChemBio will build Korea’s first plant dedicated to radiopharmaceuticals after agreeing to a $25.5 million contract with North Jeolla Province and the city of Jeongeup. The facility will combine radioisotope production, drug manufacturing and export. Construction is scheduled to begin in mid-2027, targeting a 2029 opening.
The US Food and Drug Administration (FDA) in August approved Revolution Medicines’ drug for the most common form of pancreatic cancer. The RAS inhibitor Rasonque (daraxonrasib) is a first-in-class drug targeting metastatic pancreatic adenocarcinoma. Shortly after, in September, an early-stage trial showed that the drug also has promise in lung cancer. These results bolster hopes that RAS inhibitors such as Rasonque could help combat a variety of hard-to-treat cancers such as pancreatic, lung and colorectal tumors.
Rasonque blocks multiple forms of the RAS protein — mutated KRAS and other RAS proteins present in over 90% of pancreatic tumors. Unlike traditional KRAS G12C- inhibitors like Lumakras (sotorasib) and Krazati (adagrasib), which bind the ‘off’ state of the protein, Rasonque binds the RAS GTPase in its GTP-bound ‘on’ conformation that drives oncogenic signaling. The drug works through a molecular glue mechanism, binding to both the abundant cellular protein cyclophilin A and RAS, preventing RAS from interacting with its signaling partners.
The US Food and Drug Administration has given the green light to Ionis Pharmaceuticals’ Zanvastro (zilganersen), the first disease-modifying drug for a rare, progressive and often fatal neurological condition known as Alexander disease. Zanvastro is an antisense oligonucleotide that targets RNA encoding glial fibrillary acidic protein (GFAP), which is overexpressed in astrocyte cells in Alexander disease because of mutations in the GFAP gene.
Zanvastro works by reducing GFAP overproduction in astrocytes. If there is too much GFAP, it forms clumps that cause astrocytes to malfunction and disrupt myelination in nerve-cell axons. People with Alexander disease have impaired motor function, seizures, intellectual disability and developmental delays; it affects about one person out of every 1–3 million.
A disease that has troubled white button mushroom growers for more than 100 years is far more complicated than scientists previously believed. Researchers at the University of Florida have discovered that the problem involves a surprisingly diverse collection of harmful bacteria, rather than a single pathogen. The finding could help explain why the disease has been so difficult to control and lead to more effective ways to protect mushroom crops.
The discovery comes from a University of Florida study investigating bacterial blotch, a persistent disease that damages white button mushrooms and causes significant financial losses for growers.
White button mushrooms are a valuable specialty crop and a familiar ingredient in everything from salads and appetizers to everyday meals. Rich in nutrients and valued for their versatility, they are often promoted as an example of the “food is medicine” concept, which emphasizes the role of nutritious foods in supporting good health. Their nutritional benefits make them an important part of many healthy diets.
Despite their popularity, these mushrooms face a longstanding problem that can make entire portions of a harvest difficult or impossible to sell.
A Century-Old Mushroom Disease With Hidden Culprits
Bacterial blotch causes brown or yellow discoloration on mushroom surfaces, damaging their appearance and reducing their commercial value. The disease can also lower crop yields and shorten shelf life, making it a costly challenge for mushroom farms across the United States.
Adding to the difficulty, visible symptoms sometimes develop only after mushrooms have been shipped to grocery stores or purchased by consumers. This delayed appearance makes the disease especially troublesome for growers trying to ensure consistent product quality.
For many years, scientists primarily associated bacterial blotch with a single disease-causing bacterial pathogen. However, researchers at the University of Florida Institute of Food and Agricultural Sciences (UF/IFAS) have now found that the disease involves a much more complex collection of pathogenic bacteria.
These microorganisms can thrive in the carefully controlled, humid indoor environments used for commercial mushroom cultivation. Because several bacterial species may contribute to the same disease, methods designed to target a single pathogen may not be sufficient.
“For years, the industry has struggled with treatments that provide inconsistent results against bacterial blotch,” said Samuel Martins, co-author and assistant professor in the UF/IFAS Department of Plant Pathology. “As part of a separate $7 million U.S. Department of Agriculture grant involving Penn State, University of Delaware and UF/IFAS, we are developing advanced diagnostics and sustainable solutions to strengthen mushroom farms nationwide.”
DNA Analysis Reveals More Than 17 Bacterial Species
To investigate what was causing the disease, the research team collected affected mushrooms from several production facilities across the southern United States.
The scientists combined DNA sequencing, chemical profiling and conventional laboratory testing to identify the bacteria associated with the damaged mushrooms. DNA sequencing allowed them to examine the genetic identities of microorganisms present in the samples, while the additional tests helped characterize the bacteria and their disease-causing potential.
The results revealed a far more diverse group of pathogens than expected.
“We found more than 17 different species of pathogenic bacteria associated with the disease,” said Sameerika Mudiyanselage, the study’s lead author and a doctoral student of Martins and Romina Gazis at UF/IFAS Tropical Research and Education Center. “While two well-known bacterial pathogens dominated the known disease profile, we also detected a surprisingly high level of another group of bacteria that has not previously been linked to the mushroom disease.”
The discovery suggests that scientists have been overlooking important contributors to bacterial blotch. Although two established pathogens remained prominent, the presence of additional bacterial groups indicates that the disease cannot be fully understood by studying those organisms alone.
This complexity may help explain why bacterial blotch has persisted for generations despite efforts to manage it. When several different microorganisms are associated with a disease, identifying the responsible bacteria, predicting outbreaks, and developing consistently effective treatments become more challenging.
The findings also suggest that growers may need more comprehensive detection methods capable of identifying a broader range of bacterial threats.
“We hope that expanding our research will lead to the development of better diagnostics and more effective treatments to address the full group of disease-causing bacteria in white button mushrooms,” she said.
Natural Treatments Could Help Protect Mushroom Farms
The University of Florida researchers are now building on their findings with a follow-up study focused on more sustainable ways to manage bacterial blotch.
One promising approach involves testing plant-based essential oils, beneficial microorganisms, and other biological products as possible alternatives to conventional chemical treatments.
Essential oils contain naturally occurring compounds produced by plants, some of which have antimicrobial properties. Beneficial microbes may also help suppress harmful bacteria or make it more difficult for disease-causing organisms to thrive.
These approaches could eventually offer mushroom growers additional tools for controlling bacterial blotch while reducing their reliance on conventional chemical treatments. However, further research is needed to determine how well the potential alternatives work under real growing conditions.
“Ultimately, our goal is to provide growers with practical, science-based solutions that help strengthen mushroom farming systems,” said Martins. “By understanding the complexity of bacterial blotch and the role of microbial communities, we can develop better eco-friendly management practices that reduce losses while improving sustainability.”
The research changes the understanding of a disease that has affected white button mushroom production for more than a century. Rather than being the work of a single bacterial pathogen, bacterial blotch involves a diverse group of potentially harmful microorganisms, including previously overlooked species.
By uncovering this hidden complexity, scientists hope to improve disease detection, develop more reliable treatments, and reduce the crop losses that have long burdened mushroom producers. The findings could ultimately help make mushroom farming more resilient, productive and environmentally sustainable.
Patients with a particular form of bowel cancer remained free of recurrence for almost three years after receiving a short course of immunotherapy before surgery, according to new findings from the NEOPRISM-CRC clinical trial led by researchers at UCL and UCLH.
The results, which are due to be presented at the American Association for Cancer Research (AACR) Annual Meeting 2026 in April, extend earlier findings from the trial. Those initial results showed that nine weeks of treatment with the immunotherapy drug pembrolizumab before surgery caused major tumor shrinkage in people with stage two or three bowel cancer.
Earlier data showed that 59% of patients had no detectable signs of disease after pembrolizumab treatment and their planned bowel cancer surgery.
Zero Recurrences After 33 Months
After 33 months of follow-up, none of the patients treated in the trial had experienced a return of their cancer. That was true both for patients who had no signs of cancer after treatment and for those who still had small amounts of disease remaining. In the latter group, the remaining cancer did not grow or spread during follow-up.
By comparison, around 25% of patients treated with the standard approach of surgery followed by chemotherapy are expected to relapse within three years. The findings suggest that giving a short course of immunotherapy before surgery may provide more durable cancer control for this specific type of bowel cancer than the usual combination of surgery and post-operative chemotherapy.
Researchers also studied blood samples to investigate why the treatment worked so well and to find ways of identifying which patients were most likely to benefit. They developed personalized blood tests designed to show early whether treatment had worked and whether traces of cancer were still circulating in the bloodstream.
Dr. Kai-Keen Shiu, Chief Investigator of the trial from UCL Cancer Institute and a Consultant Medical Oncologist at UCLH, said: “Seeing that no patients have experienced a cancer recurrence after almost three years of follow-up is extremely encouraging and strengthens our confidence that pembrolizumab is a safe and highly effective treatment to improve outcomes in patients with high-risk bowel cancers.
“What is particularly exciting is that we now may be able to predict who will respond to the treatment using personalized blood tests and immune profiling. These tools could help us tailor our approach, identifying patients who are doing well and may need less therapy before and after surgery versus patients at higher risk of disease progression or relapse who need additional treatment.”
Bowel Cancer Survival Varies by Stage
Bowel cancer is the fourth most common cancer in the UK, with roughly 44,000 new cases diagnosed each year. It continues to affect older adults most often, although rates among people younger than 50 have been rising in recent decades.
As with many cancers, outcomes are much better when bowel cancer is detected early. Around nine in ten people treated for stage one bowel cancer survive for at least five years. However, some tumor sub-types respond less effectively to treatment and are more likely to return. Five-year survival drops to 65% for stage three bowel cancer and 10% for stage four disease.
The NEOPRISM-CRC trial enrolled 32 patients with stage two or three bowel cancer and a particular genetic profile (MMR deficient/MSI-high bowel cancer) at five hospitals across the UK. Around 10-15% of people with stage two or three bowel cancer have this genetic make-up, equivalent to roughly 2,000-3,000 cases each year in the UK.
Instead of undergoing surgery followed by three to six months of chemotherapy, participants received up to nine weeks of pembrolizumab before their bowel surgery. Researchers then continued monitoring them over time.
Personalized Blood Tests Could Guide Treatment
The latest phase of the ongoing trial, presented this month at AACR in San Diego, California, was led by UCL and UCLH. University Hospital Southampton, St. James’s University Hospital in Leeds and the Christie NHS Foundation Trust in Manchester also helped recruit patients and supplied valuable translational samples. All translational work was carried out by UCL and biotechnology company Personalis.
Professor Marnix Jansen, a clinician scientist and consultant histopathologist who is leading the translational research on the trial from UCL Cancer Institute and UCLH, said: “These results not only confirm the durability of responses we saw almost three years ago, but also provide crucial biological insights into why immunotherapy is so effective in this setting.”
Researchers found that changes in tumor DNA in the bloodstream closely reflected how well patients were responding. Disappearance of tumor DNA from the blood was strongly associated with having no cancer remaining.
Yanrong Jiang, first author of the latest abstract and clinical PhD student at the UCL Cancer Institute, said: “As a research team, we were thrilled to be able to follow patients very closely using the personalized blood tests. When tumor DNA disappeared from the blood, patients were much more likely to have no cancer remaining, and this matched the long-term results we’re now seeing.
“In addition, we also saw that immune profiling from tumor tissue, before patients start their first cycle of treatment, can help to predict response. We hope these tests may be used to guide treatment decisions in a more practical and timely way.”
Patient’s Story
UCLH patient Christopher Burston was diagnosed with bowel cancer in February 2023 after taking part in routine screening. He had completed bowel screening kits sent through the post for several years before one test came back positive.
Christopher, 73, of Portland, Dorset, said: “One came back with indications of blood in my stool. I went through further tests, and it was at the colonoscopy that they identified a cancer in my bowel.”
A few weeks after his diagnosis, Christopher’s oncologist told him he might qualify for the NEOPRISM clinical trial, which was testing immunotherapy before surgery. Although taking part meant traveling to London for treatment, he chose to enroll and was referred to UCLH.
He received three doses of immunotherapy across nine weeks before undergoing surgery in May 2023. Christopher experienced few side effects and recovered well after spending one week in the hospital.
He said: “The outcome of the surgery was essentially that the cancer had melted away, these were the doctor’s words. The immunotherapy had had an almost immediate effect. I saw the images when I had the first colonoscopy and could see it was really quite a substantial lump. So as I say, it wasn’t a minor thing, I was diagnosed with stage 3 cancer.”
More than three years later, Christopher remains cancer-free. He has returned to his normal activities while continuing to attend regular follow-up appointments.
Christopher said: “The recovery went fine. I didn’t have any problems. And since then, I’ve been feeling pretty much back to normal. I feel very lucky that I’ve reached the stage where my main problem is age rather than cancer or any illness.”
A health worker from the Mfou District Hospital collects a blood sample for the study. [Sandrine Nsango, PhD]
Malaria is one of the deadliest infectious diseases on the planet, afflicting people for the entirety of recorded history. In places where malaria is most common, it’s shaped human evolution by driving higher rates of a protective genetic change. Two copies of the genetic change cause sickle cell disease, but one copy helps protect people from malaria. More specifically, sickle cell hemoglobin (HbS) confers protection against symptomatic malaria caused by Plasmodium falciparum.
Now, a new study has found that people with the sickle cell variant are almost exclusively infected by a distinct variety of malaria parasites, which might contribute to their lower rates of disease.
“Sickle cell trait may protect against malaria, not only by changing how the human host responds to infection, but also by shaping which parasites are able to survive and establish infection,” says Sandrine Nsango, PhD, associate professor of molecular biology at the University of Douala and researcher at the Centre Pasteur du Cameroun, Head of the Department of Biomedical Sciences, Faculty of Science, University of Bertoua.
Previous work had discovered the unusual strain of malaria by investigating the rare cases where people with the sickle cell variant develop disease symptoms. The new research extends these findings to asymptomatic infections, in which people are infected by the parasite but don’t get sick. While less visible than the disease itself, asymptomatic infections were extremely common, affecting three-quarters of the healthy study population.
HbS carriers with symptomatic malaria harbor parasites enriched for P. falciparum sickle-associated alleles (Pfsa+). While these may partially overcome HbS-mediated protection, their role in asymptomatic infections is unclear. Researchers analyzed the genetics of over 2,246 healthy schoolchildren in a region of high malaria transmission in Mfou, Cameroon, as well as the malaria parasites infecting them. The team found that people with and without the sickle cell variant tend to be infected by genetically different varieties of malaria parasites.
In addition, specific varieties of the parasite infect people with and without the sickle cell variant at similar overall rates. They write, “analyzing the parasite Pfsa and the human HbS genotypes for 1,701 asymptomatic P. falciparum infections confirmed that heterozygous HbS (HbAS) and homozygous non-HbS (HbAA) genotypes have similar rates of asymptomatic infection.” However, despite being infected at similar rates, people carrying the sickle cell variant are much less likely to develop symptomatic malaria.
The researchers found that which parasites are present in an asymptomatic infection differs based on if the infected person has the sickle cell variant. They write, “the HbS genotype is strongly associated with parasites carrying the Pfsa+ alleles at the Pfsa1 and Pfsa3 loci, indicating a selective advantage for these alleles in HbS carriers.” These findings suggest that the sickle cell variant influences which parasites can infect a person, whether or not they develop disease symptoms.
People with the sickle cell variant are just as likely to become infected—albeit with a different variety of the parasite—but they’re a tenth as likely to develop harmful disease. These observations suggest that the biological characteristics of this parasite variety may contribute, at least in part, to the protection against disease conferred by the sickle cell trait.
To understand why people with sickle cell don’t get disease as often—and use that knowledge to develop better therapies—researchers should not only look at the biology of the sickle cell variant but also investigate the differences in the malaria parasite.
Nsango says that their findings emphasize that malaria is an example of a continued evolutionary interaction between humans and the parasite. “The sickle cell mutation is one of the clearest examples of how infectious diseases can shape human evolution, but our findings suggest that humans also shape the evolution of the parasite in return,” Nsango says. “Understanding these interactions may help us anticipate how malaria parasites adapt in the future and design more effective strategies for malaria control.”
Studies of the immune system show that two people born on the same day can have immune systems that age differently, leaving some older adults with resilient defense systems and others with dysfunctional ones that put them at increased risk for age-related diseases. Now a new study led by scientists at Washington University School of Medicine in St Louis, Nationwide Children’s Hospital in Ohio, and King’s College London provides a map of human immune aging that could help explain these different trajectories. Details are published in a new Immunity paper titled “Single-cell analyses of global cohorts outline determinants of immune aging and link the ratio of GZMK⁺ to GZMB⁺ Tem cells to health trajectories.”
According to the paper, a ratio between two immune cell types can reveal whether someone stays healthy or may face risk of future disease. To get to this insight, the scientists first analyzed approximately 12.4 million individual immune cells from the blood of over 2,600 mainly healthy adults ages 20 to 90-plus across eight cohorts in North America, the United Kingdom, Asia, and Australia.
Their analysis showed that while the blood of younger people was uniformly enriched with naive immune cells that had not been exposed to specific pathogens and remained adaptable to new infections or vaccines, older immune systems were more diverse. Specifically, some older participants had a greater abundance of immune cells that reflect inflammation.
To map this shift, the researchers placed each participant on a spectrum based on the ratio between two types of white blood cells: specifically, granzyme B-producing cells and granzyme K-producing cells. Some white blood cells, known as effector memory CD8 T cells, use granzymes to destroy target cells or coordinate immune responses. While granzyme B-producing cells serve as direct destroyers of diseased cells, granzyme K-producing cells have been less studied and may play a role in boosting immune responses.
Next, the researchers evaluated whether participants’ positions on the spectrum, which corresponds to a specific type of CD8 T cell, could dictate their risk of getting sick. In other words, they looked at whether having more of one type of CD8 T cell has an impact on the person’s health as they age. To answer that question, the scientists turned to the UK Biobank.
While that dataset includes protein information from the participants, it lacks counts of CD8 T cells. To get around this hurdle, the scientists used a smaller dataset of seemingly healthy adults that included data on CD8 T cell counts and blood proteins to create a computer model to map out the protein tracks left behind when either granzyme B-producing or granzyme K-producing cells dominated. They then applied this model to the baseline blood protein samples of 50,000 participants from the UK Biobank, calculating their position on the immune cell spectrum.
Using this approach, the scientists were able to draw out some useful insights for their work. Specifically, they found that healthy adults whose immune system leaned heavily toward granzyme B cells at baseline tipped the scale toward a higher risk of death a decade later compared to those with more granzyme K cells. The granzyme B-dominant group also was more likely to develop chronic conditions, including Type 2 diabetes, hypertension, liver disease, and renal failure, among others, over the following decade.
“A higher level of granzyme B cells in a healthy state means the immune system might be already reacting to something,” said Marina Terekhova, MD, a professor in pathology & immunology at WashU Medicine and one of the co-authors on the paper. “It isn’t a formal disease diagnosis, but it may indicate the body is off track.”
A healthy immune system gradually shifts toward granzyme K cells over time, while an immune system that leans toward granzyme B cells signals unhealthy aging. Because individuals can reach this granzyme B state much earlier in life, their immune systems age on different trajectories, explaining why two people born in the exact same year can face different risks for chronic disease and death decades later.
These findings point to “clues in the blood that can tell us whether someone is on a healthy or unhealthy aging trajectory,” said Maxim Artyomov, PhD, the alumni endowed professor of pathology and immunology at WashU Medicine and one of the corresponding authors on the paper. Artyomov and his lab are now adapting their research into a simple blood test that can be processed using standard equipment. “Identifying specific biological red flags in the immune system could pave the way for early-warning tests that spot disease risks years before a clinical diagnosis.”
Molecular movie of penicillin biosynthesis. X-ray free electron laser experiments on isopenicillin N synthase microcrystals capture structural snapshots of key intermediates during the penicillin forming reaction. The film strip illustrates progression through the catalytic cycle, with the monocyclic β-lactam intermediate and reactive high valent ferryl iron species highlighted at the center of the molecular movie. [University of Oxford/Greg Stewart/SLAC National Accelerator Laboratory]
Researchers from the University of Oxford and international collaborators have revealed previously unseen rapid chemical stages in the formation of β-lactam antibiotics such as penicillin, offering insights that could help to support future antibiotic development.
Rather than relying on static X-ray crystallographic structures of the enzyme, the Oxford University team, collaborating with partners from Diamond Light Source, Lawrence Berkeley National Laboratory, PAL-XFEL, and SLAC National Accelerator Laboratory, followed the reaction in real time. To do this they used X-ray free-electron lasers (XFEL) to observe the enzyme isopenicillin N synthase, (IPNS) as it converts its linear peptide substrate into the β-lactam ring system of penicillin.
The study brought together expertise in structural biology, spectroscopy, chemistry, computation and enzyme engineering. The approach, they say, provides a powerful way to study fleeting chemical intermediates that have previously been inaccessible, both in antibiotic biosynthesis and in other biologically important enzyme reactions.
The team captured several rapid stages in the reaction. These included a thioaldehyde intermediate formed just before the β-lactam ring is created, and a monocyclic β-lactam intermediate, representing the first ring-shaped structure on the way to forming the complete penicillin scaffold. These steps provide the clearest picture yet of how the IPNS enzyme assembles the penicillin scaffold. Subtle movements throughout the enzyme help guide these chemical steps, showing that both the enzyme’s shape and its chemistry work together to control penicillin formation.
The results show, in unprecedented detail, how the enzyme IPNS achieves an exceptionally complex transformation in a single step. Christopher Schofield, PhD, Professor of Chemistry, University of Oxford, said, “Penicillin has shaped modern medicine, but there is still much to learn about how nature builds this important antibiotic structure. By capturing these fleeting steps, we can better understand how enzymes control complex chemistry with remarkable precision … As rates of antimicrobial resistance continue to rise, understanding this process will ultimately help us make existing antibiotics more efficient and design new antibiotic structures.”
Allen M Orville, PhD, group leader of the XFEL Hub, further commented, “The XFEL Hub at Diamond brought specialist expertise in time-resolved X-ray methods and XFEL-based structural biology to this study. Working closely with our colleagues in Oxford and at partner facilities, we helped bring together the experimental approaches needed to capture these fleeting stages of enzyme catalysis. The results show the power of combining complementary expertise and X-ray techniques to move beyond static structures and reveal how enzymes work in real time. It is a great example of how time-resolved structural biology can uncover new principles of enzyme function and, ultimately, inform the design of new catalysts and therapeutics.”
Ever since penicillin was developed into a working drug at the University of Oxford in the early 1940s, β-lactam antibiotics have been among the most important medicines for treating bacterial infections. Their activity depends on a special ring—the β-lactam ring—a highly strained chemical ring system that interferes with bacterial cell wall synthesis, ultimately causing the cell wall to fail and the bacteria to die. “Isopenicillin N synthase (IPNS) catalyses the biosynthesis of isopenicillin N (IPN), forming the fused four-membered β-lactam and five-membered thiazolidine ring system that is characteristic of the penicillins,” the authors explained.
Rising rates of antimicrobial resistance are undermining the effectiveness of existing antibiotics. Today, one in six bacterial infections is resistant to antibiotics, the authors noted, citing WHO figures. With too few new antibiotics in development, understanding how nature builds these molecules is an important step towards replenishing the antibiotic pipeline.
Scientists have been studying how nature constructs this β-lactam ring for decades, but the key fleeting reaction intermediates have been too difficult to observe directly.
To capture the reaction in real time, the researchers used a system in which thousands of tiny droplets containing anaerobic enzyme microcrystals were deposited onto a moving 2 mm wide tape. As the tape entered an oxygen filled chamber, oxygen rapidly diffused into the crystals and initiated the reaction simultaneously across the sample. By precisely controlling the speed of the tape, the researchers could determine how long each crystal reacted before reaching the X-ray interaction point, where an ultrafast XFEL pulse recorded an atomic resolution snapshot.
Combining thousands of these snapshots allowed the team to build a frame-by-frame “molecular movie” of penicillin biosynthesis. This method allows individual reaction intermediates that exist only for tiny fractions of a second to be observed at atomic resolution, and under physiological temperature and pressure, before they disappear.
The newly reported findings help to resolve a long-standing mechanistic question that has remained unanswered for more than four decades. The work also showed that water molecules inside the enzyme play a key role in guiding the reaction. The combined results of their studies, they noted, “… reveal unexpected insight into the IPNS reaction mechanism including the vital roles of active-site water molecules.”
The study ultimately builds on the work of Nobel prize-winning Oxford chemist Dorothy Hodgkin, PhD, who first solved the structure of penicillin in 1945 using X-ray crystallography.
Beyond penicillin, IPNS belongs to a large family of iron-dependent oxygenase enzymes involved in human biology, including those that enable us to sense and respond to changes in oxygen availability. The mechanistic insights from this work could therefore have implications beyond antibiotics, offering new principles for enzyme engineering and catalyst design.
“These findings provide structural insight into IPNS catalysis, inform on the wider Fe(II) oxygenase superfamily and highlight the power of X-ray free-electron laser methods for resolving transient enzymatic intermediates,” the team stated in their paper. First author Patrick Rabe, PhD, Wellcome Career Development Award Investigator, University of Oxford, said, “These insights matter because they can inform how we think about antibiotic biosynthesis and future strategies for developing antibacterial medicines. The ability to capture structural snapshots over milliseconds to seconds of reaction time allows us to connect enzyme motion, iron chemistry and water-mediated proton transfer. This gives us a much richer view of how IPNS controls a difficult chemical transformation. By understanding this process in atomic detail, we can begin to think about engineering these enzymes to produce new or improved antibiotic scaffolds.”
Multiomics analysis combines data from two or more omics layers—such as genomics, transcriptomics, proteomics, and epigenomics. However, published criticisms of multiomics approaches have highlighted concerns about data integration and a tendency toward false-positive findings.1–3
What additional roadblocks might accompany ambitious multiomics projects in 2026? Could any bottlenecks emerge in cost, sample preparation, data integration, or AI implementation? We recently interviewed experts from five companies to gain their perspectives. Here is what they had to say.
Sample preparation
“I sound like a broken record because I can’t stop talking about the importance of sample prep in multiomics work,” says Michael Easterling, PhD, vice president of MALDI/Imaging at Bruker Daltonics.
Easterling stresses challenges such as section-to-section variability, internal standards, FFPE samples, and long sample runs that complicate downstream algorithms. “For multiomics imaging, these issues are not as well defined as some of the bulk methods that have been around much longer,” he notes.
Scott Jelinsky, PhD, senior director of R&D at Thermo Fisher Scientific, agrees. “Different molecular classes have different requirements for sample collection, storage, and preparation,” he says. “Therefore, careful experimental design and standardization are essential.”
Easterling mentions the consequences of inadequate freezing during biopsies, which can disrupt cell structures and lead to ice crystal artifacts. “It is important to really make sure that you have a solid workflow to correctly harvest tissue and provide a good chain of custody from the point that it’s harvested all the way to the analyzer.”
What are some tips for multiomics researchers hoping to prepare their samples in an optimal way? “Community networking is key here,” argues Easterling. “I would say get involved with the overall spatial imaging community and network and find out exactly how to do these things.”
Another practical consideration, according to Jelinsky, is planning the workflow from the beginning so that sample collection, aliquoting, storage, and analytical requirements are compatible across different assays. “Decisions made early in the study can have a significant impact on what can be measured and how confidently the different datasets can be interpreted together,” he notes.
Data integration and analysis
Multiomics technologies generate vast amounts of high-resolution data across modalities that often behave differently from a statistical perspective, notes Najiba Mammadova, PhD, associate director of product management at 10x Genomics. “Multiomics assays have advanced incredibly quickly, and now the analysis and interpretation tools need to keep pace,” she notes.
Mammadova specifically highlights the challenges of computationally aligning multiple omics from different cells or tissues. After all, how can researchers be certain that they are measuring the same cells and biological features?
The 10x Genomics MultiPro Human Discovery Panel, which integrates into existing Flex scRNA-seq workflows, is the largest antibody-based, single-cell protein panel, enabling integrated analysis of 326 protein targets. [10x Genomics]
“That’s why I think measuring multiple modalities from the same cell or tissue is so important,” she adds. “It reduces the need to reconstruct the biology after the fact and gives researchers a more direct view of what’s happening in the sample.”
Vanee Pho-Conners, PhD, vice president of global marketing at Mission Bio, agrees that data integration is often a major hurdle with multiomics work. “Each omics layer has its own data structure, distributions, and variabilities, so combining them isn’t plug-and-play,” she explains. Multiomics analysis also often requires cross-disciplinary expertise in biostatistics, machine learning, and biology—capabilities many labs lack in-house.
“It’s important to ask how you can combine these data sets in a clean way where you preserve all the information, reduce the noise, and start to make biological inferences,” adds Easterling. “It’s not something that’s routine today, but the situation is changing rapidly, and new ways to integrate these datasets of varying dimensionality are starting to appear.”
Timing is yet another important consideration, notes Jelinsky. Proteins, RNA, and metabolites may exhibit different kinetics and respond on different timescales, so measurements collected at the same time may not always align. “Understanding those temporal relationships is essential when integrating and interpreting the results,” he says.
Thermo Fisher’s multiomics solutions include services as well as products for sample preparation, separation, acquisition, and analysis. [Thermo Fisher]
AI and multiomics
“I think the rate-limiting multiomics questions are shifting from ‘Can we measure this?’ to ‘Can we interpret it?’ And that’s where AI has enormous potential,” notes Mammadova. “We’re generating increasingly rich, high-dimensional datasets, and AI can help researchers identify patterns, interpret those data more quickly, and ultimately build models that can predict things like disease progression or treatment response.”
However, Easterling warns that even the most advanced AI technologies often cannot overcome challenges associated with inadequate sample preparation. “Unfortunately, if a model’s trained on an inconsistently prepared section, it’ll give you a confident biological story that’s completely wrong. And the reader of this data may have no way to tell.”
The DNA, RNA, and protein workflow on Tapestri’s single-cell platform. Each cell is encapsulated in its own droplet, and a unique molecular barcode (specific to each cell) gets attached to each DNA, RNA, and protein molecule. [Mission Bio]
As an example of recent AI advances, Easterling highlights multiomic workflows pioneered at the Medical University of South Carolina for single-cell analysis. The group has developed an AI algorithm that assists lasers in targeting individual cells rather than clusters of cells.4 Pho-Conners also emphasizes how Mission Bio is using machine learning to jointly cluster DNA, RNA, and protein—referred to as triomics—from the same cell. “We are using a combination of triomics and AI-driven integration to establish disease resistance. This really goes beyond correlations using a single omics layer,” she says.
Although Jelinsky is generally optimistic about AI advances in multiomics, he foresees fundamental limitations. “I see AI as a tool that can help researchers navigate complexity and generate better hypotheses rather than as a replacement for scientific judgment. AI does not remove the need for rigorous experimental design or biological validation,” he stresses.
Challenges with extracellular vesicles
Distinct multiomics challenges also exist in analyzing extracellular vesicles (EVs), small membrane spheres released by cells that contain multiple omics (DNA, RNA, protein, metabolites, and lipids).
“EVs are how cells talk to each other, and a living cell sends up to ten thousand a day. This makes them good biomarkers,” says Pierre Arsène, founder and CEO of Mursla Bio.
However, with traditional EV analysis, each potential omics layer is measured from EVs derived from an unknown blend of cells. There is usually no way to know whether a protein signal and an RNA signal came from the same tissue, for instance.
Mursla’s biomarker discovery workflow for tissue-specific extracellular vesicles. Antibody-coated magnetic beads capture hepatocyte-derived vesicles from under two milliliters of plasma, leaving behind extracellular vesicles from other tissues. [Mursla Bio]
“Tissue-specific extracellular vesicles (TS-EVs) are how we recover that record,” explains Arsène. Mursla’s technology begins with a blood draw. Liver-specific EVs are then captured using antibodies against proprietary surface markers (more specifically, hepatocyte-EV markers). Finally, proteomics and RNA sequencing are performed on two milliliters of plasma for biomarker discovery.
“The great thing about TS-EVs is that they arrive addressed, carrying surface proteins specific to the sending cell and sealed behind a membrane that shields proteins and RNA from the enzymes that would destroy them in blood.”
EvoLiver, Mursla’s blood test for liver cancer surveillance in cirrhotic patients, holds an FDA Breakthrough Device Designation. It analyzes three proteins and five microRNAs derived from hepatocytes. Proteins provide information about tumor surface phenotype and metabolic reprogramming, while microRNAs reveal the regulatory programs driving that phenotype.
As with so many other multiomics platforms, Arsène stresses the importance of TS-EV sample preparation. “Blood handling standards for EVs lag well behind standard liquid biopsy, so our clinical work relied mostly on prospective collection under a common protocol rather than using legacy biobanks.”
The future of multiomics
Mammadova highlights the potential for cost-related challenges in multiomics, particularly as the field moves toward larger studies. “Making these technologies more scalable and cost-effective will be critical to expanding their use across research,” she adds.
“However, I see more overall challenges than roadblocks in multiomics work,” she concludes. “They’re the kind of problems the field works through as technologies mature.”
Detection of the whole transcriptome along with over 64 proteins in a human breast cancer FFPE tissue section using Bruker’s CosMx spatial molecular imager. [Bruker Spatial Biology]
Spatial multiomic layers will also become increasingly critical for decoding the complexity of disease biology, predicts Prajan Divakar, PhD, Bruker Spatial Biology vice president of product management. “Investigators continue to demonstrate the need for more complete spatial datasets, and we are seeing clear applications and momentum for clinical translation,” he says. Divakar highlights Bruker’s CosMx® spatial molecular imager, which measures the whole transcriptome and over 64 proteins.
Finally, Arsène argues that simply adding more layers of analysis without biological resolution is unlikely to advance multiomics research in the future. For instance, in the largest study of a blood-based cancer test ever run (involving around 50,000 participants), incorporating an additional protein layer in advanced adenoma increased the sensitivity only modestly—from about 15% to 16%.5 “More and more layers allow you to gain dimensions, but you end up losing coherence. And no cohort in the world is large enough to train that coherence back computationally.”
Jelinsky agrees that the value of multiomics will lie not in generating more data, but in selecting complementary measurements that address a specific biological question. “I think the future of multiomics will be less about generating the largest possible number of measurements and more about determining which combination of measurements provides the most meaningful biological insight,” he says.
References
Behrens LMP, Fernandes GDS, Gonçalves GF, et al. Limitations and opportunities in multi-omics integration for neurodevelopmental, neurodegenerative and psychiatric disorders: A systematic review. Neuroscience. 2026;599:76-93. doi: 10.1016/j.neuroscience.2026.01.019.
Hayes CN, Nakahara H, Ono A, Tsuge M, Oka S. Genes (Basel). From Omics to Multi-Omics: A Review of Advantages and Tradeoffs. 2024;15(12):1551. doi: 10.3390/genes15121551.
Baião AR, Cai Z, Poulos RC, et al. A technical review of multi-omics data integration methods: from classical statistical to deep generative approaches. Brief Bioinform. 2025;26(4):bbaf355. doi: 10.1093/bib/bbaf355.
Dressman JW, Bayram MF, Angel PM, Drake RR, Mehta AS. Single-Cell Multiomic MALDI-MSI Analysis of Lipids and N-Glycans through Affinity Array Capture. Anal Chem. 2025;97(24):12493-12502. doi: 10.1021/acs.analchem.4c06233.
Shaukat A, Burke CA, Chan AT, et al. Clinical Validation of a Circulating Tumor DNA-Based Blood Test to Screen for Colorectal Cancer. JAMA. 2025;334(1):56-63. doi: 10.1001/jama.2025.7515.
Detection of the whole transcriptome along with over 64 proteins in a human breast cancer FFPE tissue section using Bruker’s CosMx spatial molecular imager. [Bruker Spatial Biology]