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Drilling down on treatment-resistant fungi with molecular machines

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Drilling down on treatment-resistant fungi with molecular machines

Newly developed molecular drills may be able to fight treatment-resistant fungal infections like Candida auris.
Dr_Microbe/iStock via Getty Images

Ana L. Santos, Rice University; Jacob Beckham, Rice University, and James Tour, Rice University

Fungi are present on the skin of around 70% of the population, without causing harm or benefit. Some fungal infections, like athlete’s foot, are minor. Others, like Candida albicans, can be deadly – especially for individuals with weakened immune systems.

Fungal infections are on the rise because of an aging population and an increased prevalence of chronic diseases. At the same time, fungi are becoming more resistant to treatment. As a result, fungal infections could soon become a serious public health threat.

In 2022, the World Health Organization released its first-ever “Fungal Priority Pathogen List,” calling for improved surveillance, public health interventions and the development of new antifungal drugs.

We are an interdisciplinary team of chemists and biologists charting a new path to tackle drug-resistant infections. We are using tiny nanoscale drills that combat harmful pathogens at the molecular level. As the traditional antimicrobial research pipeline struggles, our approach has the potential to rejuvenate the fight against these stubborn infections.

Molecular machines as alternative antifungals

While doctors urgently need new antifungal drugs, developing them is challenging. First, it is difficult to develop drugs that selectively kill fungi without harming human cells because of their many similarities.

Second, fungi can rapidly develop resistance to multiple antifungal drugs at once when medications are misused or overused. As such, developing antifungal drugs is much less rewarding for drug companies than developing medications for chronic conditions like diabetes and hypertension that require long-term use.

One solution to this problem could lie in a Nobel Prize-winning technology: molecular machines.

Molecular machines are synthetic compounds that rapidly rotate their components at about 3 million times per second when exposed to light. Doctors can use a light-tipped probe to activate these molecular machines to treat internal infections, or a lamp for skin infections. The light starts the machines spinning, and that rotational motion pushes them to drill through and puncture the cell’s membranes and organelles, which results in cell death.

Our group first used this technology to kill cancer cells in 2017. To target the right cells, molecular machines can be linked to specific peptides that bind only to the desired cells, allowing, for instance, the targeting of specific cancer types. Since then, we have used these molecules to kill bacteria, destroy tissue and stimulate muscle contraction. These properties make molecular machines an enticing candidate technology to address the growing fungal threat.

A diagram showing the structure of a molecular machine as gray lines connected in the shape of several hexagons
The 3D structure of a molecular machine. The molecular machine consists of rotor (top) and stator (bottom) portions connected by a central axle. Following light activation, molecular machines rotate rapidly, drilling into fungal cells.
Tour Lab, Rice University

Testing antifungal molecular machines

Researchers first tested the ability of light-activated molecular machines to kill fungi in Candida albicans. This yeastlike fungus can cause life-threatening infections in immunocompromised people. Compared with conventional drugs, molecular machines killed C. albicans much faster.

Subsequent studies found that molecular machines could also kill other fungi, including molds like Aspergillus fumigatus and species of dermatophytes, the types of fungi that cause skin, scalp and nail infections. Molecular machines even eliminated fungal biofilms, which are slimy, antimicrobial-resistant communities of microorganisms that stick together on surfaces and commonly cause medical device-associated infections.

Unlike conventional antifungals, which target the fungal cell membrane or cell wall, molecular machines localize to the fungal mitochondria. Often referred to as the “powerhouses of the cell,” mitochondria produce energy to power other cellular activities. When activated with visible light, molecular machines destroy the fungal mitochondria. Once the fungal cell’s mitochondria stop working, the cell loses its energy supply and dies.

Two black-and-white electron microscopy images of a fungal cell. The left image shows a large, round, healthy cell, while the cell on the right is shrunken following treatment with light-activated molecular machines.
Candida albicans before and after being exposed to light-activated molecular machines. Molecular machines puncture C. albicans‘ cell wall and intracellular organelles, eventually killing the fungal cell.
Matthew Meyer/Rice University.

At the same time, molecular machines also disrupt the tiny pumps that remove antifungal agents from the cell, thus preventing the cell from fighting back. Because these molecular machines act by a mechanical instead of a chemical mechanism, fungi are unlikely to develop defenses against this treatment.

In lab experiments, combining light-activated molecular machines with conventional antifungal drugs also reduced the amount of fungi in C. albicans-infected worms and in pig nails infected with Trichophyton rubrum, the most common cause of athlete’s foot.

New frontiers for fighting fungal infections

These results suggest that combining molecular machines with conventional antifungals can improve existing therapies and provide new options for treating resistant fungal strains. This strategy could also help reduce the side effects of traditional antifungals, such as gastrointestinal upset and skin reactions.

Fungal infection rates will likely continue to rise. As such, the need for new treatments will only become more urgent. Climate change is already causing new human pathogenic fungi to emerge and spread, including Candida auris. C. auris is often resistant to treatment and spread rapidly in health care facilities during the COVID-19 pandemic. According to the Centers for Disease Control and Prevention, strained health care systems, overuse of immunosuppressants and misuse of antibiotics have all been implicated in outbreaks of C. auris.

In the future, researchers could use artificial intelligence to create better antifungal molecular machines. By using AI to predict how different molecular machines will interact with fungi and human cells, we can develop safer and more effective antifungal molecules that specifically kill fungi without harming healthy cells.

Antifungal molecular machines are still in the early stages of development and are not yet available for routine clinical use. However, continuing research gives hope that these machines could one day provide better treatments for fungal infections and other infectious diseases.The Conversation

Ana L. Santos, Postdoctoral Fellow in Microbiology, Rice University; Jacob Beckham, Graduate Student in Chemistry, Rice University, and James Tour, Professor of Chemistry, Rice University

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Commerce oversees everything from weather and salmon to trade and census − here are 3 challenges awaiting new secretary

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theconversation.com – Linda J. Bilmes, Daniel Patrick Moynihan Senior Lecturer in Public Policy and Public Finance, Harvard Kennedy School – 2025-01-28 14:05:00

Commerce oversees everything from weather and salmon to trade and census − here are 3 challenges awaiting new secretary

Howard Lutnick, left, is President Donald Trump’s nominee to run the Commerce Department.
AP Photo/Evan Vucci

Linda J. Bilmes, Harvard Kennedy School

The U.S. secretary of commerce oversees the smallest but arguably most complex of all Cabinet-level departments.

Established as a distinct entity in 1913, it has evolved into a sprawling organization with 13 bureaus spanning a wide variety of critical areas that include weather forecasting, conducting the census, estimating gross domestic product, managing fisheries, promoting U.S. exports, setting standards for new technology and allocating radio frequency spectrum. It is even home to one of America’s eight uniformed military services, the NOAA Commissioned Officer Corps with its own fleet of ships, aircraft and 321 commissioned officers. Its main mission is to monitor oceans, waterways and the atmosphere in support of the National Oceanographic and Atmospheric Administration.

As a result, there is no other Cabinet position that has to engage with lawmakers in Congress across so many disparate technical issues, committees and stakeholders. This medley reflects both the historical evolution of the U.S. economy and a degree of political happenstance.

I served at the Commerce Department in several roles, including as chief financial officer and assistant secretary for administration, management and budget, and have watched several administrations attempt to craft an overarching strategic narrative around this diverse set of missions.

Besides the difficult job of formulating a unifying strategy for the department’s many activities, I believe there are three specific challenges in particular that await the next secretary, a position that requires Senate confirmation.

A male coho salmon with red gills emerges from a creek
The Commerce Department manages salmon as part of its National Marine Fisheries Service.
AP Photo/Manuel Valdes

Commerce: A sprawling bureauocracy

From its earliest days, the Commerce Department has collected trade statistics, overseen lighthouses and issued patents and trademarks. But since then, its portfolio has expanded significantly.

In 1970, NOAA was placed inside Commerce, partly as a result of a feud between President Richard Nixon and his interior secretary, Wally Hickel, over the Vietnam War. NOAA now accounts for more than half the department’s US$11 billion budget and has created some peculiar departmental overlaps.

As President Barack Obama joked in his 2011 State of the Union speech, “The Interior Department is in charge of salmon while they’re in freshwater, but the Commerce Department handles them when they’re in saltwater.”

While the joke wasn’t quite accurate – a division of Commerce manages salmon in both fresh and saltwater, though Interior does restore their habitat – it does reflect some odd situations. For example, when it comes to sea turtles, Interior oversees their nests on shore, whereas Commerce protects them in the open sea.

Due to the department’s broad interests, the commerce secretary has a role in nearly every important issue facing the country.

He or she needs to be a quick study who is able to multitask, respond to congressional inquiries on a myriad of topics, as well as manage a 50,000-strong workforce including economists, scientists, statisticians, meteorologists and other experts.

One example of the caliber of experts Commerce oversees is the National Institute for Standards and Technology, which does cutting-edge research in bioscience, artificial intelligence, materials science and industrial measurement standards. The institute currently has five Nobel laureates in physics and chemistry on its staff and is on the front lines on cybersecurity and national defense.

While it’s unclear how Trump nominee Howard Lutnick plans to unify Commerce’s work, the previous secretary, Gina Raimondo, outlined five strategic goals for her department, including driving U.S. global competitiveness, using data to find new opportunities and modernizing its services and capabilities.

The Senate Committee on Commerce, Science and Transportation is holding a hearing on Jan. 29, 2025, to consider Lutnick’s nomination.

Challenge No. 1: Another census is just around the corner

The incoming secretary’s biggest challenge will be the decennial census due on April 1, 2030.

The census counts every person living in the U.S. and five U.S. territories. Census data is used to apportion the number of seats each state has in the House of Representatives and to adjust or redraw electoral districts, as well as to apportion federal funding allotted to each district. Consequently, the census receives huge attention in Congress. It will be an especially hot topic because the data collected in the 2020 census had errors due to the pandemic.

Conducting the census is highly labor intensive and takes many years of planning and preparation, which ramp up now.

The Commerce Department must hire 500,000 temporary workers, open local offices and run large-scale field tests, award billions of dollars in contracts, and work with every state, local, county and tribal government in the country to map where people live. This includes dorms, homeless shelters, nursing homes, prisons, oil rigs, boats, tents, hospitals and mobile homes as well as houses and apartments.

The Census Bureau says it began planning for 2030 as far back as 2019 and is preparing to do a test census in 2026.

Trump administration policies, such as ongoing efforts to round up and deport undocumented migrants, will make it even more challenging to count immigrants and other historically hard-to-reach groups. During his first term, President Donald Trump sought to prevent unauthorized immigrants from being counted at all – but ran out of time.

a group of people wearing identical blue suits and some wearing hats stand and talk in the hull of a plane
A NOAA crew on a reconnaissance flight into the eye of Hurricane Milton in October 2024.
Sim Aberson/NOAA via AP

Challenge No. 2: NOAA on the front lines of climate change fight

Second, NOAA is likely to be in the political crosshairs, due to its role as a global leader in studying oceans, climate and coastal ecosystems.

It tracks rising sea levels, ocean acidification and extreme weather events, and forecasts their impact on fisheries, shipping, marine protected areas and habitats. It also runs the National Weather Service and issues severe storm warnings. These and many other NOAA activities are vital to monitoring the pace of climate change and helping Americans adapt.

NOAA’s mission and its budget are sure to be scrutinized by the Trump administration, which has already reversed a variety of policies meant to slow the pace of climate change. Trump himself has called climate change a “hoax.” That and policy proposals that seek to break up or privatize NOAA suggest many of NOAA’s climate-related activities could be under threat.

Challenge No. 3: The patent problem

A third challenge the incoming secretary will face is an ongoing crisis at the Patent and Trademark Office.

Unlike most federal agencies, the Patent and Trademark Office is funded by user fees collected from applicants rather than from tax revenue. This is supposed to make it more efficient and easier to hire staff quickly, but the model is under stress due to a shortage of patent examiners with skills in assessing science, technology, engineering and math applications. The agency currently has a backlog of over 800,000 unexamined patent applications – near an all-time high.

The backlog is likely to continue to grow as artificial intelligence and other state-of-the-art technologies accelerate the discovery cycle, but the slow process of patent approval – two years on average – can throw a wrench in it.

Patents and trademarks are critical to U.S. competitiveness because they reward innovation and discovery and help inventors attract investors.

The Trump administration’s broad federal hiring freeze is likely to worsen the Patent and Trademark Office’s staffing issues, while the back-to-office mandate may make it harder to recruit patent examiners, who often work remotely.

On top of this, Elon Musk, whose companies hold large numbers of patents and who already holds tremendous sway in the Trump administration, says “patents are for the weak” and compared them with landmines in warfare. “They don’t actually help advance things,” he said. “They just stop others from following you.”

In addition to these three areas, Commerce’s roles in international trade, telecommunications, industrial security and other matters could also become epicenters of any global crisis.

This all adds up to an uncomfortable mix of political and operational challenges for the next secretary.

This story is part of a series of profiles explaining Cabinet and high-level administration positions.The Conversation

Linda J. Bilmes, Daniel Patrick Moynihan Senior Lecturer in Public Policy and Public Finance, Harvard Kennedy School

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Students in this course use systems thinking to help solve human rights, disease and homelessness

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theconversation.com – Raúl Ordóñez, Professor of Electrical and Computer Engineering, University of Dayton – 2025-01-28 07:51:00

Engineering the social: Students in this course use systems thinking to help solve human rights, disease and homelessness

An engineering education can equip students to work on broader social issues.
Photosomnia/E+ via Getty Images

Raúl Ordóñez, University of Dayton

Uncommon Courses is an occasional series from The Conversation U.S. highlighting unconventional approaches to teaching.

Title of course:

Engineering Systems for the Common Good

What prompted the idea for the course?

As a control systems researcher, I have long felt that control systems – and systems science in general – have much to contribute to solving social problems.

Control systems make other systems behave in some desired manner. Think of the cruise control in a car, which keeps its speed constant, or the thermostat in a house that regulates temperature.

I wanted to know whether engineers could treat society and social phenomena as systems in the engineering sense. That way, students and researchers could mathematically model and even simulate these phenomena using computers.

Control systems engineering offers a set of powerful analysis and design tools. I wanted to know whether my students and I could apply these methods to things such as policymaking to help address societal problems.

What does the course explore?

In this course, students learn fundamental systems theory concepts, such as block diagrams, feedback loops and discrete-time dynamics. They apply these concepts to mathematically model and analyze social systems.

In the class, I talk with the students about human rights. We think about how this powerful idea applies to social systems. This systems framework helps us approach social justice issues in a methodical, mathematical manner.

A professor standing in the front of a classroom, pointing at a screen projector.
In Raúl Ordóñez’s class at the University of Dayton, students take engineering concepts and apply them to societal issues.
Shawn Robinson/University of Dayton

Students use simulation software to model systems such as disease epidemics, the viral spread of ideas, the tragedy of the commons and homelessness, among others.

Importantly, they learn that some social phenomena can be methodically studied and engineered, in a quantifiable manner. For example, they can use numbers and data to experiment and evaluate how introducing vaccines affects disease spread.

By the end of the course, students gain a deeper understanding of the connection between engineering principles and tools and human rights and society.

Why is this course relevant now?

This course helps bridge the gap between engineering and social sciences by bringing concepts from human rights and social justice to engineering students. It teaches them how the powerful engineering tools they learn throughout the engineering curriculum can directly serve the common good.

What’s a critical lesson from the course?

The course is a concrete step toward teaching engineering and science students that engineering has more to offer to society than its direct applications. Students learn that a partnership between the humanities and engineering is not only possible but strongly desirable for the advancement of the common good.

What materials does the course feature?

There is no one textbook that deals with all the topics in this course, although the book “Humanitarian Engineering: Advancing Technology for Sustainable Development,” third edition, by Kevin M. Passino, is a very useful resource. I have mostly developed my own materials, including my set of lecture notes, projects and numerical simulation code.

Many engineers use tools in engineering to help people and communities.

What will the course prepare students to do?

The course aims to prepare students to apply common engineering tools such as differential equations, signals and systems, systems analysis, mathematical models and numerical simulation to the analysis of social problems, with an emphasis on human rights implications.

It also introduces social modeling as a powerful method for understanding social issues and assessing how various policies affect human rights.

My goal is to produce engineering students who can meaningfully contribute to policymaking by using engineering tools to assess the consequences of social and economic policies.The Conversation

Raúl Ordóñez, Professor of Electrical and Computer Engineering, University of Dayton

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Medical research depends on government money – even a day’s delay in the intricate funding process throws science off-kilter

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theconversation.com – Aliasger K. Salem, Associate Vice President for Research and Professor of Pharmaceutical Sciences, University of Iowa – 2025-01-28 07:51:00

Medical research depends on government money – even a day’s delay in the intricate funding process throws science off-kilter

Of the tens of thousands of grant applications submitted to the National Institutes of Health, only around 1 in 5 is funded.
Sean Gladwell/Moment via Getty Images

Aliasger K. Salem, University of Iowa

In the early days of the second Trump administration, a directive to pause all public communication from the Department of Health and Human Services created uncertainty and anxiety among biomedical researchers in the U.S. This directive halted key operations of numerous federal agencies like the National Institutes of Health, including those critical to advancing science and medicine.

These operations included a hiring freeze, travel bans and a pause on publishing regulations, guidance documents and other communications. The directive also suspended the grant review panels that determine which research projects receive funding.

As a result of these disruptions, NIH staff has reported being unable to meet with study participants or recruit patients into clinical trials, delays submitting research findings to science journals, and rescinded job offers.

Shorter communication freezes in the first few days of a new administration aren’t uncommon. But the consequences of a freeze lasting weeks or potentially longer underscore the critical role the federal government plays in supporting biomedical research. It also brings the intricate processes through which federal research grants are evaluated and awarded into the spotlight.

I am a member of a federal research grant review panel, as well as a scientist whose own projects have undergone this review process. My experience with the NIH has shown me that these panels come to a decision on the best science to fund through rigorous review and careful vetting.

How NIH study sections work

At the heart of the NIH’s mission to advance biomedical research is a careful and transparent peer review process. Key to this process are study sections – panels of scientists and subject matter experts tasked with evaluating grant applications for scientific and technical merit. Study sections are overseen by the Center for Scientific Review, the NIH’s portal for all incoming grant proposals.

A typical study section consists of dozens of reviewers selected based on their expertise in relevant fields and with careful screening for any conflicts of interest. These scientists are a mix of permanent members and temporary participants.

I have had the privilege of serving as a permanent chartered member of an NIH study section for several years. This role requires a commitment of four to six years and provides an in-depth understanding of the peer review process. Despite media reports and social media posts indicating that many other panels have been canceled, a section meeting I have scheduled in February 2025 is currently proceeding as planned.

Person wearing glasses reviewing a stack of papers, surrounded by other stacks of papers on a desk
Evaluating projects for their scientific merit and potential impact is an involved process.
Center for Scientific Review

Reviewers analyze applications using key criteria, including the significance and innovation of the research, the qualifications and training of the investigators, the feasibility and rigor of the study design, and the environment the work will be conducted in. Each criterion is scored and combined into an overall impact score. Applications with the highest scores are sent to the next stage, where reviewers meet to discuss and assign final rankings.

Because no system is perfect, the NIH is constantly reevaluating its review process for potential improvements. For example, in a change that was proposed in 2024, new submissions from Jan. 25, 2025, onward will be reviewed using an updated scoring system that does not rate the investigator and environment but takes these criteria into account in the overall impact score. This change improves the process by increasing the focus of the review on the quality and impact of the science.

From review to award

Following peer review, applications are passed to the NIH’s funding institutes and centers, such as the National Institute of Allergy and Infectious Diseases or the National Cancer Institute, where program officials assess the applications’ alignment with the priorities and budgets of institutes’ relevant research programs.

A second tier of review is conducted by advisory councils composed of scientists, clinicians and public representatives. In my experience, study section scores and comments typically carry the greatest weight. Public health needs, policy directives and ensuring that one type of research is not overrepresented relative to other areas are also considered in funding decisions. These factors can change with shifts in administrative priorities.

Grant awards are typically announced several months after the review process, although administrative freezes or budgetary uncertainties can extend this timeline. Last year, approximately US$40 billion was awarded for biomedical research, largely through almost 50,000 competitive grants to more than 300,000 researchers at over 2,500 universities, medical schools and other research institutions across the U.S.

Getting federal funding for research is a highly competitive process. On average, only 1 in 5 grant applications is funded.

Scientist looking into microscope, surrounded by other lab equipment
Medical research often follows a strict timeline.
gorodenkoff/iStock via Getty Images Plus

Consequences of an administrative freeze

The Trump administration’s initial freeze paused some of the steps in the federal research grant review process. Some study section meetings have been postponed indefinitely, and program officials faced delays in processing applications. Some research groups relying on NIH funding for ongoing projects can face cash flow challenges, potentially resulting in a need to scale back research activities or temporarily reassign staff.

Because my own study section meeting is still scheduled to take place in February, I believe these pauses are temporary. This is consistent with a recent follow-up memo from acting HHS Secretary Dorothy Fink, stating that the directive would be in effect through Feb. 1.

Importantly, the pause underscores the fragility of the research funding pipeline and the cascading effects of administrative uncertainty. Early-career scientists who often rely on timely grant awards to establish their labs are particularly vulnerable, heightening concerns about workforce sustainability in biomedical research.

As the NIH and research community navigate these pauses, this chapter serves as a reminder of the critical importance of stable and predictable funding systems. Biomedical research in the U.S. has historically maintained bipartisan support. Protecting the NIH’s mission of advancing human health from political or administrative turbulence is critical to ensure that the pursuit of scientific innovation and public health remains uncompromised.The Conversation

Aliasger K. Salem, Associate Vice President for Research and Professor of Pharmaceutical Sciences, University of Iowa

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