Wednesday, May 07, 2025

 

Research collaboration takes ‘one health’ approach to study Chagas disease exposure, treatment effectiveness


Supported by almost $4 million in new funding, researchers in the Texas A&M College of Veterinary Medicine and Biomedical Sciences and University of Georgia are working to develop interventions that will impact both canine and human health



Texas A&M University

Chagas disease 

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Dr. Ashley Saunders and Dr. Sarah Hamer from Texas A&M University’s College of Veterinary Medicine and Biomedical Sciences will be working with a professor from the University of Georgia to gain a better understanding of Chagas disease, which affects both people and dogs.

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Credit: Texas A&M University




A team of researchers at Texas A&M University and the University of Georgia (UGA) has received more than $4 million from federal and non-governmental organizations to support research on Chagas disease prevalence, diagnostics and treatment to benefit both dogs and humans.

Chagas disease is a tropical illness caused by the parasite Trypanosoma cruzi, which is most commonly spread by the fecal matter of triatomine bugs — also known as “kissing bugs” because they bite their hosts to feed on blood. The disease — common in humans and dogs — often goes unnoticed in early stages, but a chronic infection can lead to serious heart and digestive system problems, making early diagnosis important.

Dr. Sarah Hamer, a professor in the Texas A&M College of Veterinary Medicine and Biomedical Sciences’ (VMBS) Department of Veterinary Integrative Biosciences; Dr. Ashley Saunders, a professor and cardiologist in the VMBS’ Department of Small Animal Clinical Sciences; and Dr. Rick Tarleton, UGA Regents Professor and UGA Athletic Association Distinguished Professor, are leading the projects.  

“These projects will advance Chagas disease research to understand the process of natural infections, disease and effect of treatments,” Hamer said. “These projects combine many aspects of biomedical research. We’re conducting field and laboratory research, treating dogs, measuring clinical outcomes and studying ecological factors. It’s truly a ‘One Health’ approach.”

Both privately owned and working dogs in Texas provide an important source of data for Chagas disease because they often encounter kissing bugs.

“Unfortunately, Texas has emerged as a hotspot of infected kissing bugs, infected wildlife and infected dogs across the landscape,” Hamer said. “We think dogs are getting infected when they eat the insects.”

“Dogs that work in customs and border protection and for the Transportation Security Administration can be exposed to Chagas disease,” Saunders said. “Some of our work will be a continuation of previous studies of the clinical impacts of the disease on canine cardiac health, as well as how the dogs are exposed to the parasite so we can help minimize their risk.”

Advancing Human Health By Studying Dogs 

Although most human cases of Chagas disease are reported from South and Central America and Mexico, there are established kissing bug populations across the southern United States, including Texas. The infection and disease is notoriously difficult to detect and treat.

To address these issues, one project, funded by the National Institutes of Health, will use innovative diagnostic and treatment strategies to establish optimal protocols for detection and treatment of the infection, so as to optimally prevent the development of cardiac disease. 

“There are a number of important questions related to treatment efficacy and the protection that cured subjects have from future infection that cannot be easily addressed in humans, but can be in these dog populations that are under intense transmission pressure in Texas,” Tarleton said.

Currently, diagnosis of Chagas disease is complicated by several factors — some diagnostic tests work by looking for the parasite’s DNA in the host’s blood, but if an individual has very low levels of parasite DNA or the test isn’t sensitive enough to detect the DNA, the test may return a negative result. In addition, T. cruzi’s life cycle includes parasites that are dormant, and thus resistant to treatment.

To address these issues, the new study will track infected individuals using a combination approach with sensitive tests to detect both the parasite DNA and the body’s response to infection, while treating with an antiparasitic drug in a modified regimen. 

Because the disease presents similarly in dogs as in humans, dogs are a good model for examining the effectiveness of the treatment, and because the researchers will be working with dogs who already have Chagas disease, owners are highly motivated to support the work.

“The drug we’re using is an existing treatment for Chagas disease in humans,” Saunders said. “But Dr. Tarleton has shown that the parasites aren’t susceptible to this drug when they’re dormant. By changing the drug delivery protocol to dosing over a longer period of time, when the dormant parasites become active again, they are killed by the drug.”

“The project is unique because we are studying privately owned hunting dogs in large kennel environments that have, unfortunately, become naturally infected with T. cruzi,” Hamer said. “Many of these owners have had other dogs die from the disease, so they want to help us solve the problem.”

Fighting Chagas Disease In Government Working Dogs

In another project, funded by the United States Department of Homeland Security (DHS), the researchers will monitor DHS-owned working dogs that are often trained in areas where Chagas disease is prevalent to understand how they are exposed to the disease as well as the impacts it can have on heart health.

This project also includes Dr. Heather Manley Lillibridge, the executive director of Texas A&M’s Cross-Border Threat Screening and Supply Chain Defense, a Center of Excellence in partnership with the DHS, through which the project is being run. 

“One of the reasons that monitoring dogs is so helpful is because Chagas disease can produce so many different subsets of health problems,” Saunders said. “Some dogs end up with a heart abnormality, but a large number continue living and working happily for many years. Others will die quite suddenly, before anyone knew they had the disease.” 

“Recording health information from such a large population of dogs will hopefully help us understand why the disease develops in different ways,” Hamer said.

Government working dogs are commonly trained in Texas to detect things such as explosives or drugs, but they may perform their jobs for customs, border patrol and transportation systems anywhere in the U.S. As such, dogs could acquire an infection in the South — where kissing bugs occur — and later be transported to other regions of the country where the disease hasn’t traditionally occurred and where there is little veterinary awareness.   

Advancing Canine Chagas Disease Management 

In a third project, with continued support from the American Kennel Club Canine Health Foundation, the team will treat and monitor individual pet dogs brought to Texas A&M’s Small Animal Teaching Hospital while developing a staging system for Chagas disease in dogs. 

“The staging system we develop will help us to categorize the severity of disease, making it easier to determine which dogs will benefit most from drug treatment,” Saunders said. “This scoring system will work hand-in-hand with our improved diagnostic and treatment plan.”

These projects are among Hamer’s, Saunders’ and Tarleton’s ongoing efforts to better understand, diagnose and treat Chagas disease. One of those, the Kissing Bug Community Science Program, has been accepting and testing kissing bugs submitted from around the U.S. for more than a decade. Kissing bugs are most commonly encountered by people and animals in the southern U.S. in summer months. 

For more information on these and Texas A&M’s other Chagas disease-related studies, visit vetmed.tamu.edu/chagas

By Texas A&M University College of Veterinary Medicine and Biomedical Sciences

 

Cracking the code: deciphering how concrete can heal itself



Dr. Congrui Grace Jin and her team have unlocked a novel way for concrete to mend its own cracks, potentially preventing structural failures and saving lives



Texas A&M University




Imagine concrete healing its own cracks like human skin recovering from a cut. That’s the vision behind the latest research of Dr. Congrui Grace Jin, published in Materials Today Communications

Addressing one of the most persistent and expensive problems in construction, Jin, an assistant professor in the Department of Engineering Technology and Industrial Distribution, has taken inspiration from nature to develop a synthetic lichen system to enable concrete to self-repair.

Concrete is the most widely used building material on Earth, yet it suffers from the dangerous flaw of cracking easily. These cracks, big or small, can lead to catastrophic structural failure, as witnessed in the collapse of a building, bridge or highway.

The key to overcoming this critical challenge lies in understanding how concrete forms and how to exploit that process. Concrete is made by mixing crushed stone and sand with powdered clay and limestone. When water is added, the combination hardens through a chemical reaction called hydration. Once set, it becomes strong enough to support everything from 18-wheelers crossing bridges to people living in towering skyscrapers. However, natural forces like freeze-thaw cycles, drying shrinkage and heavy loads cause cracks. Even those barely visible to the naked eye can allow liquids and gasses to reach embedded steel reinforcements, causing corrosion and weakening structures. 

Discovering cracks before they endanger lives is a high-stakes and costly challenge, with the U.S. annually spending tens of billions of dollars repairing concrete infrastructure. Locating cracks in bridges and highways that are constantly in use is especially difficult.

“Microbe-mediated self-healing concrete has been extensively investigated for more than three decades”, says Jin, “but it still suffers from one important limitation — none of the current self-healing approaches are fully autonomous since they require an external supply of nutrients for the healing agents to continuously produce repair materials.” For example, after inspectors go through the laborious process of locating a crack, they may then have to inject or spray nutrients into the crack, which is not practical.

Jin’s solution? Harness the power of lichen systems to allow concrete to heal itself without outside intervention. 

Lichen is an understated presence in our everyday world, often found clinging to trees and rocks. Its true beauty lies in its unique symbiotic system of fungi and algae, or cyanobacteria, that form a self-sustaining partnership, allowing it to thrive in even the harshest conditions.

With that inspiration, Jin and her researchers, Dr. Richard Wilson, Nisha Rokaya and Erin Carr of the University of Nebraska-Lincoln, with funding by the Young Faculty Award program of DARPA, created a synthetic lichen system that collaborates like natural lichens. 

Their system uses cyanobacteria, which turns air and sunlight into food, and filamentous fungi, which produces minerals that seal the cracks. Working together, these microbes survive on nothing more than air, light and water. The autonomy of this system sets it apart from previous self-healing concrete endeavors.

In lab tests, these microbe pairs were able to grow and produce crack-filling minerals even in challenging environments such as concrete.

Jin takes her work beyond the lab to consider wider implications. She is collaborating with professors from Texas A&M University’s social science departments to develop a better understanding of the public’s perception about using living organisms in construction and the ethical, social, environmental and legal issues involved.

This groundbreaking research has far-reaching potential and applications. Concrete that can heal itself could significantly reduce maintenance costs, extend its longevity and even protect lives through increased safety. It can also have a dramatic impact in all areas of sustainable construction, including space infrastructure.

By Jennifer Nichols, Texas A&M University College of Engineering

 

A faster route to eliminating parasitic infection endemic to Africa



In a clinical trial, researchers find moxidectin, a new medicine for river blindness, also works for lymphatic filariasis




WashU Medicine

A faster route to eliminating parasitic infection endemic to Africa 

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Philip Budge, MD, PhD (center), an associate professor in the Division of Infectious Diseases at WashU Medicine, speaks with collaborators Benjamin Koudou of the Centre Suisse de Recherches Scientifiques (CSRS) in Côte d'Ivoire (left) and Catherine Bjerum, MD, of Case Western Reserve University. Their recent clinical trial finds the anti-parasitic drug moxidectin – currently approved to treat river blindness, another tropical disease caused by parasitic worms – is also more effective for lymphatic filariasis than the current gold standard, ivermectin.

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Credit: Matt Miller




Tens of millions of people in Africa are infected by parasitic worms that cause lymphatic filariasis (also called elephantiasis), a disease that leads to severe swelling and deformities of the limbs and genitals. Despite widespread treatment programs that have successfully reduced the risk of contracting lymphatic filariasis, hundreds of millions of people remain vulnerable to the infection.

A small clinical trial in Cote d’Ivoire, led by researchers at Washington University School of Medicine in St. Louis, shows that the anti-parasitic drug moxidectin – currently approved to treat river blindness, another tropical disease caused by parasitic worms – is also more effective for lymphatic filariasis than the current gold standard, ivermectin. Moreover, because moxidectin has a persistent effect in most treated individuals, it may need fewer rounds of treatment, compared with annual treatment for at least five years for ivermectin, pointing to the possibility of accelerating the elimination of the infection in Africa.

This study appears May 6 in The Lancet Infectious Diseases.

“Moxidectin really works much better than the drugs that we’re currently using against lymphatic filariasis,” said Philip Budge, MD, PhD, an associate professor of medicine in the Division of Infectious Diseases at WashU Medicine and the senior author of the study. “The fact is, in most of Africa, lymphatic filariasis and onchocerciasis, or river blindness, are co-endemic and you really need a drug that is going to work well for both of them.”

The trial was conducted in collaboration with the Centre Suisse de Recherches Scientifique in Côte d’Ivoire. Lymphatic filariasis is endemic to many African countries, and more than 26 million people are estimated to be at risk for infection in Cote d’Ivoire alone. The parasite that causes the disease, Wuchereria bancrofti, is spread by mosquitoes.

River blindness, which causes itching, rashes, skin nodules and vision impairment (which, left untreated, can lead to permanent blindness) is endemic in many of the same countries as lymphatic filariasis. Both diseases have been targeted for elimination by global programs enacted by the World Health Organization (WHO). For lymphatic filariasis, the administration of anti-parasitic medications to nearly 1 billion people so far represents the largest mass drug administration initiative for any infectious disease. In addition to limb swelling, lymphatic filariasis may increase the risks of patients contracting other diseases such as malaria, tuberculosis and HIV/AIDS.

Typically, people must receive annual doses of ivermectin and another anti-parasitic drug, albendazole, for five years to fully clear the infection. The aim of this study was to determine whether moxidectin, a new medicine for river blindness, shown to be superior to ivermectin in combatting that disease, could be a better option in combination therapies for treating lymphatic filariasis.

Participants in the trial – all adults ages 18 to 70 – had high blood concentrations of microfilaria, the larvae of adult worms. Those with high concentrations are considered infectious, contributing to the continued spread of this disease.

The study involved four treatment groups, each of which received combinations of either moxidectin or ivermectin with one or two other drugs commonly used to treat parasitic worm infections.

After 12 months, 18 out of 19 participants in the group that received moxidectin and another drug (albendazole) had cleared their infections, compared to 8 out of 25 in the ivermectin plus albendazole group. At 24 months, 14 out of 16 participants in the moxidectin group continued to remain microfilaria-free.

Among participants who received either ivermectin or moxidectin in combination with two other drugs, 21 out of 23 people in the moxidectin group were parasite-free after 24 months while 20 out of 22 participants in the ivermectin group cleared their infections over that same time period. The finding suggests that one dose of moxidectin and another drug is just as effective as moxidectin or ivermectin combined with two other drugs.

“If you treat someone with moxidectin, they are more likely to clear their parasites for longer,” said Budge. “With ivermectin, people must be treated multiple times. So, maybe the right place for moxidectin in the global elimination program is in people who are hard to reach repeatedly.”

Budge explained that many people who are missed by mass drug administration programs are difficult to re-dose because they live in remote villages.

Medicines Development for Global Health, a not-for-profit pharmaceutical company in collaboration with the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) developed moxidectin for human use.

“The best possible outcome for this work long-term would be for moxidectin to be used in mass drug administration programs,” Budge said. “That would shorten the number of years we need to achieve lymphatic filariasis elimination. There are hundreds of millions of people who won’t have this disease in the future if we can eliminate it, and moxidectin may be able to help accelerate that process.”

Koudou GB, Bjerum CM, Ouattara FA, Gabo TK, Goss CW, Lew D, Dje N’GN, King CL, Fischer PU, Weil GJ, Budge PJ. Moxidectin combination therapies for lymphatic filariasis: an open label, observer-masked, randomised controlled trial. The Lancet Infectious Diseases. May 6, 2025. DOI: 10.1016/S1473-3099(25)00111-2

This publication is based on research funded by (or in part by) the Gates Foundation. The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Gates Foundation.

About Washington University School of Medicine

WashU Medicine is a global leader in academic medicine, including biomedical research, patient care and educational programs with 2,900 faculty. Its National Institutes of Health (NIH) research funding portfolio is the second largest among U.S. medical schools and has grown 56% in the last seven years. Together with institutional investment, WashU Medicine commits well over $1 billion annually to basic and clinical research innovation and training. Its faculty practice is consistently within the top five in the country, with more than 1,900 faculty physicians practicing at 130 locations and who are also the medical staffs of Barnes-Jewish and St. Louis Children’s hospitals of BJC HealthCare. WashU Medicine has a storied history in MD/PhD training, recently dedicated $100 million to scholarships and curriculum renewal for its medical students, and is home to top-notch training programs in every medical subspecialty as well as physical therapy, occupational therapy, and audiology and communications sciences.

 

Biologists create a one-stop shop for world’s most charismatic plants




Florida Museum of Natural History
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The Florida Museum of Natural History has partnered with 35 herbarium collections across the United States to create a web portal for ferns.

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Credit: Photo by Michael Sundue




The Florida Museum of Natural History has partnered with 35 herbarium collections across the United States to create a web portal for ferns.

Wait! Hear me out. You’re probably thinking, “Ferns? The plants with the curly leaves that grow in shady places? Why should I care?”

I’m glad you asked. Ferns — and a related group called lycophytes — have been around in one form or another for more than 400 million years. This group of plants, collectively called pteridophytes, was the first to develop roots and leaves, which it did long before dinosaurs were even a gleam in evolution’s eye. They were the first plants to evolve the botanical equivalent of a circulatory system, which allowed them to grow into the first trees.

Ferns, lycophytes and other early offshoots altered Earth’s previously barren landscapes, breaking up bare rock with their roots and dissolving it in acid, a process that pulls carbon dioxide from the atmosphere. They did this so thoroughly that it caused an ice age, resulting in the second mass extinction of life on Earth. And that’s only the first 50 million years of their evolutionary history. It only gets more interesting from there. But in the interest of time, we’ll skip to the present.

Today, there are more than 10,000 species of ferns and lycophytes, making them the second-most diverse group of vascular plants (the ones with a circulatory system, which includes anything that produces seeds).

“You can’t understand plant diversity without including ferns,” said Michael Sundue, an integrative taxonomist at the Royal Botanic Garden Edinburgh in Scotland and co-author of a new paper announcing the fern portal and describing its various applications.

The project was funded by the National Science Foundation and had two main goals. The first was to create an online repository to store information about fern specimens stored in museums around the world. That was the easy part. Next came the daunting task of getting all that information digitized and uploaded to the portal. Many museums have plant specimens collected over hundreds of years that haven’t yet made their way online, primarily because the process of digitizing specimens takes a lot of time and money. The NSF grant helped pay for some of that.

“There were hundreds of thousands of records that were digitized specifically for this project,” said co-author Lucas Majure, curator for the University of Florida herbarium, which has uploaded more than 14,000 of its own specimens to the portal.

Museums are using the same digitization process for all plant and animal specimens, not just ferns. The result is an online catalogue of life, and if you’re a biologist who studies diversity, this tool has become indispensable.

“The availability of digitized resources has fundamentally changed how we do science,” Sundue said.

In the paper, the authors list three examples of how the online database, called the PteridoPortal, has already contributed to our understanding of the natural world. Among them is an effort to inventory the fern and lycophyte diversity of Colombia, a country that straddles the equator and is home to some of the most diverse ecosystems on Earth. Beginning in 1964 and lasting several decades, Colombia was also embroiled in civil strife that left little room for active participation in the natural sciences.

“Colombia is one of the most biodiverse countries on Earth, but it is very undersampled,” said Sundue, who is one of the primary scientists working on the inventory.

Conducting a biological survey for an entire country can quickly become a logistical nightmare. Even the first step of figuring out what’s already been documented can be despairingly difficult.

Before museums began digitizing specimen data, researchers had to physically travel to those institutions and locate specimens spread throughout the collections to verify they’d been correctly identified and record when and where they’d been found. If they made it to the next step, they’d conduct field expeditions to fill in any gaps by collecting new specimens. All this information would be compiled in a notebook or a spreadsheet, and eventually, after years of hard work, researchers would share what they’d learned by publishing a book.

Notably absent from these books were the many thousands of specimen records that were used to write it, as these would have taken up an obscene amount of space. If you wanted to do a follow-up study on someone’s work, you either had to contact the people who wrote the book and hope they’d share their data, or you had to start from scratch.

Instead of doing that, Sundue and his colleagues used the fern portal. Before embarking on expeditions to Colombia, they searched the portal for ferns from the areas they planned to visit, which they used to create a list — complete with images — of what to look for. Information about the specimens they collect goes directly into the fern portal, where it’s immediately available to other users. They can still publish a book if they want to, but the critical information is already online.

The NSF grant only supported digitization at 17 nonfederal institutions, but the PteridoPortal is open to everyone, and others agreed to share their data, including the Smithsonian National Museum of Natural History, the Naturalis Biodiversity Center in the Netherlands and the ETH Zurich in Switzerland. While working on the separate Colombia project, Sundue also collaborated with institutions in the area to help supplement and jump-start their own digitization programs.

We helped the botanical garden of Medellín to get all their data online, and we’re going to try to do that with the University of Antioquia as well,” he said.

Lucas Majure is also working with colleagues to implement the portal for collections at the Jardín Botánico Nacional in the Dominican Republic. Future collaborative efforts like these are likely to follow.

The portal has enough bells and whistles to make the average biologist lightheaded with excitement, but the real utility of the application, and others like it, is the boost it gives to biodiversity monitoring. Biologists are a long way from taking full stock of what lives on our planet, and species throughout the tree of life are disappearing before they’ve even been discovered.

As we continue into what’s widely referred to as Earth’s sixth mass extinction event (this one caused by humans, not ferns), it’s imperative for scientists to deploy every tool they have to document what’s left and, ideally, prevent the worst of future losses.

“If we don’t continue to learn and teach people about biodiversity, no one will notice when it disappears,” Sundue said.

 

Why bumbling bees prefer yellow flowers to red – and why it matters for biodiversity




John Innes Centre
Bumble 

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Curious and colourful example of biodiversity - Yellow and Red Mimulus cardinalis 

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Credit: Dr Katie Wenzell




Some years ago, scientists examining wild plants in a western corner of the United States encountered a curiously colourful example of biodiversity. 

Two species of red Mimulus (monkeyflowers) normally pollinated by hummingbirds (Mimulus cardinalis and Mimulus verbenaceus) have unusual, yellow-flowered populations at the edge of their ranges. 

The researchers found that these rarer yellow forms seemed to be favoured by pollinating bees, but there was little information on whether other traits such as floral scent or shape were attracting them. 

Decades on, Dr Kelsey Byers’ research group at the John Innes Centre (JIC) has revisited this research using modern genomic and biochemical resources in controlled lab environments. 

The aim was to explain the genetic and biochemical basis of the colour change and to investigate how traits such as floral colour, scent and shape might be involved in an apparent pollinator shift from hummingbird to bumblebee.   

The results offer us a fascinating glimpse into the workings of biodiversity in nature and may help us engineer better pollinated, higher yielding crops. 

The experiments, in controlled conditions, showed that bumblebees did indeed prefer yellow to red flowers and were twice as likely to visit them. The study also found that both types of yellow morphs had increased scent emission which could reflect selection from pollinators such as bees, which use scent to forage unlike hummingbirds. 

Intriguingly, however, the shape of the flowers presented the bees with problems to the extent that they were not good pollinators for the plant itself!  

Bumblebees were ill-fitted to the flowers, causing damage while attempting to access nectar and poorly contacting floral organs which would be a hindrance to efficient pollen transfer.  

The study suggests that these yellow flowers represent a possible early stage in the evolutionary transition, the “adaptive walk” from hummingbird to bee pollination. 

It also sheds light on the order in which floral traits may evolve in a pollinator shift, and how mutations of larger effect, in this case colour, might precede smaller changes, in scent and morphology. 

A key question, which was not answerable at the time of the previous research, was whether the yellow forms in the species M. cardinalis and M. verbenaceous had evolved convergently - that is, if their characteristics were underpinned by the same genetic differences or if they had arrived by different routes. The answer from this study is both. 

This study showed that some of these changes were indeed convergent, the yellow morphs resulting from an increase in the production of carotenoids (red-orange-yellow pigments) which were increased using the same genes in both species. 

Other traits had emerged independently by separate means - for example red pigment regulators and floral scent compounds. 

Dr Kelsey Byers, corresponding author of the study which appears in Nature Communications, said: “Even though these species are closely related, they have followed different paths to the same endpoint for many of their traits. 

“We have identified ways that flowers can change and affect pollinator visitation, as well as some genetic pathways that can underlie these changes and how they have evolved in different but closely related species.” 

The team now plans to do some functional testing of the genes that they have found that are convergent (carotenoid pathway) or divergent (anthocyanin regulators) to see how they have evolved in this system. They are also investigating another yellow population of M.cardinalis to see whether it has followed the same convergent paths or not.  

The complex partnership between plants and pollinators is essential for biodiverse ecosystems which support cleaner environments and the production of many crops. 

“By understanding how traits evolve in the wild, we understand biodiversity better, and by understanding how these traits can be affected by plant genetics, we have the foundation of the ability to engineer traits to impact pollinator preference and thus crop yield,” added Dr Byers. 

The paper ‘Within-species floral evolution reveals convergence in adaptive walks during incipient pollinator shift’ appears in Nature Communications.  

It was co-authored by former JIC postdoctoral researcher Dr Katie Wenzell and JIC research assistant Dr Mikhaela Neequaye. JIC informatics support was provided by senior bioinformatician Dr. Pirita Paajanen, and JIC metabolomics support by metabolite service manager Dr Lionel Hill, and analytical chemist Paul Brett.