Malaria: Newly identified “crown” stage controls parasite reproduction

The Hebrew University of Jerusalem

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Research Team

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Credit: Tomer Shamay

Researchers studying the malaria parasite Plasmodium falciparum have discovered a previously unknown stage in its life cycle that appears to be crucial for reproduction. This is important because malaria depends on the parasite’s rapid ability to multiply inside the human body, so stopping its reproduction could help prevent severe disease and save lives. Using a new live-imaging method, the team found that before the parasite can divide, a key structure inside the cell must reshape into a “Crown” form and connect to the cell’s nucleus. This step helps ensure that essential parts of the parasite are properly passed on to its new daughter cells. The findings point to a promising new target for future malaria treatments: interrupting the signals that control this “Crown” stage could potentially stop the parasite from multiplying.

A new study has uncovered a hidden step that helps the deadliest malaria parasite survive and multiply inside the human body. Researchers studying Plasmodium falciparum found that the parasite relies on a brief but essential stage, nicknamed the “Crown” stage, to make sure a crucial internal structure is passed on correctly when it divides. The discovery offers a fresh look at how the parasite reproduces and could point to new ways to stop malaria by disrupting this process.

Malaria remains one of the world’s most devastating infectious diseases, causing hundreds of thousands of deaths each year, most of them among young children in sub-Saharan Africa.

The research, published in the Journal of Cell Biology, was led by Dr. Anat Florentin of The Kuvin Center for the Study of Infectious and Tropical Diseases and the Department of Microbiology and Molecular Genetics in the Faculty of Medicine at Hebrew University. The team focused on a tiny structure inside the parasite called the apicoplast. While humans don’t have this organelle, malaria parasites depend on it to survive. Although the apicoplast originally came from a photosynthetic ancestor, it now functions as a kind of mini chemical factory, producing essential molecules, including fatty acids and isoprenoids, that the parasite needs to grow inside human red blood cells.

“By tracking both DNA replication and apicoplast development in real time, we found the details of these events and what controls them,” says Dr. Florentin. “There are both signals from the nucleus and intrinsic organelle cues at play. These mechanisms could provide a new opportunity for drug development: if, for example, we can interrupt the communication between the nucleus and the apicoplast, we will stop the parasite from multiplying.”

To observe what happens inside the parasite as it grows, the researchers developed an advanced live-imaging system that follows subcellular structures in high resolution across the parasite’s full 48-hour life cycle. Using this approach, they identified four stages in apicoplast development: Elongation, Branching, Crown, and Division.

The study highlights the importance of the Crown stage, a short one-hour period just before the parasite divides. During this phase, the apicoplast stretches across multiple nuclei and attaches to structures known as centriolar plaques, the parasite’s equivalent of the machinery that helps cells organize division. This connection acts like a distribution checkpoint, helping ensure that when the parasite splits, every new daughter cell receives one complete, working apicoplast.

To understand how this process is controlled, the researchers used drugs that block specific steps in the parasite’s replication:

• Blocking nuclear DNA replication: When the researchers stopped the parasite from copying its nuclear DNA using aphidicolin, apicoplast development stalled almost immediately. This showed that the apicoplast cannot grow properly unless the parasite has entered the DNA-copying phase of its cycle.
• Blocking apicoplast DNA replication: In contrast, when the team blocked the apicoplast’s own DNA replication using ciprofloxacin (CIP), the organelle still grew and formed branches but it failed to form the Crown structure.

Without the Crown stage, the apicoplast could not attach to the centriolar plaques, and daughter cells were produced without it. This leads to a phenomenon known as “delayed death.” The first generation of parasites may survive, but the next generation cannot, because without the apicoplast, the parasite is missing a structure it needs to make essential molecules and stay alive.

Overall, the findings challenge the idea that the apicoplast functions independently inside the parasite. Instead, the study suggests that the apicoplast’s development and inheritance depend on carefully timed signals from the parasite’s nucleus, especially during the newly identified Crown stage.

According to the researchers, this newly uncovered dependency may represent a promising vulnerability. By targeting the signaling mechanisms that coordinate the parasite’s DNA replication and apicoplast development, future therapies could disrupt parasite reproduction and help stop malaria by preventing the parasite from multiplying in the first place.

Coordination between organelles in the Plasmodium cell facilitates its unique cell division. The multiple nuclei (red), are connected to the apicoplast (green) by centriolar plaques (pink). This interaction happens only during the “Crown” stage and it is critical to from multiple daughter cells, each with a complete set of organelles. This image was prepared using a technique called expansion microscopy and visualized by a Confocal microscope.

A Plasmodium parasite engulfed within a red blood cell showing its nuclei (turquoise) and the apicoplast (magenta). Total protein labelling outlines the boundaries of the parasite and the host red blood cell. Coordinated alignment of the apicoplast with dividing nuclei is critical for organelle inheritance and malaria parasite reproduction. This image was prepared using a technique called expansion microscopy and visualized by a Confocal microscope.

Credit

Michal Shahar

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Journal

Journal of Cell Biology

DOI

10.1083/jcb.202504052 

Method of Research

Experimental study

Subject of Research

Cells

Article Title

Independent nuclear and organellar mechanisms determine apicoplast fate in malaria parasites

 

Norwegian prime minister Støre Presents the Mohn Prize to Canadian researcher

Professor John P. Smol was today given the Mohn Prize by Prime Minister Jonas Gahr Støre. "You are a true leader and an important contributor," said the Prime Minister to the prize winner.

UiT The Arctic University of Norway

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Price winner John Smol (centre) sorrounded by Prime Minister Jonas Gahr Støre (left) and Rector Dag Rune Olsen (right).

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Credit: David Jensen / Arctic Frontiers

John P. Smol, a professor at Queen's University in Canada, received the prize for his role in identifying the factors driving environmental changes in the Arctic. The international Mohn Prize is awarded every two years for outstanding research related to the Arctic. 

 "Professor Smol’s career illustrates the role that science can and should play: solving global challenges and communicating them to decision-makers so they can act," said Støre in his speech. 

Smol emphasised that science is a team effort, comparing himself to an ice hockey coach when receiving awards. "It’s the team that wins, but I get to lift the trophy," he said. 

"I have always had excellent teams of students and collaborators. Their contributions to our research have been remarkable," Smol added. 

Støre praised Smol for his ability to collaborate and nurture new talent: 

"By continuously highlighting and supporting everyone you work with, you demonstrate true leadership in research. For that, we all thank you," said Støre. 

Why Did Smol Receive the Prize?

The awarding of the Mohn Prize to Smol is more than an academic recognition—it is a tribute to a method that unlocks the past, enabling us to navigate the future. 

Smol is a scientific detective. His crime scene: Arctic lakes. His clues: microscopic remnants of life, preserved in sediment layers at the bottom of lakes. By reading these layers—some hundreds of thousands of years old—like the pages of a history book, he reveals how ecosystems have responded to changes over centuries. 

His work has provided methods to identify early warning signs of ecological disruptions. By studying diatoms and other microscopic organisms, he can precisely document when a lake became more acidic, when pollution first appeared, or how aquatic life changed as the climate warmed. 

This is not just academic curiosity—it is knowledge with immense practical value. Smol’s research has delivered concrete findings that have led to action against acid rain and pollution, with impacts far beyond local communities. He provides decision-makers with what they need most: a solid, scientific foundation for action. 

 

Smol has a unique ability to bridge the past and the present. He shows us that lakes have a memory. This memory is our best reference for assessing the changes we see today. Without a clear picture of what an ecosystem looked like before industrial impact, we are fumbling in the dark when setting goals for management, restoration, and conservation. 

 

When Prime Minister Jonas Gahr Støre presented the prize to Professor John P. Smol today at Arctic Frontiers, it was because Smol has shaped his field and inspired scientists worldwide. He has shown us that the small, often overlooked lakes of the Arctic are sensitive archives of the planet’s health. 

 

His work also carries a profound societal dimension. The knowledge he generates informs national and international negotiations. It is relevant to discussions on sustainable development, Indigenous rights, and the management of the fragile northern regions. 

About the Mohn Prize

• The international Mohn Prize for Outstanding Research Related to the Arctic was established in collaboration between Academia Borealis – The Academy of Sciences and Letters of Northern Norway, Tromsø Research Foundation, and UiT The Arctic University of Norway.
• The prize, worth 2 million NOK, is awarded every two years at Arctic Frontiers.
• John Smol is the fifth laureate, after Eddy Carmac (2018), Dorthe Dahl-Jensen (2020), John Walsh (2022) and Oran Young (2024).
• 
  

The laureate spoke to a packed room at Arctic Frontiers.

Credit

David Jensen / Arctic Frontiers

Prime Minister Støre emphasised Smol's contriburion to giving decicion makers a solid foundation.

Credit

Kjetil Rydland / UiT

 

Timing is everything. Why the US gets some drugs faster than other countries

Researchers find that differences in drug availability are driven more by when companies submit drugs for approval than review speed, especially for medicines that offer little added benefit to patients.

Brown University

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As Washington debates how to rein in soaring prescription drug prices, including proposals that would tie U.S. prices to those paid abroad, a new study led by researchers at the Brown University School of Public Health is challenging the long-held assumption about why Americans get new medicines sooner than patients in other countries.

For years, drug companies and industry allies have argued that the U.S. gets faster and wider access because its government moves quicker than foreign regulators, but the new analysis suggests the U.S. advantage in drug access is driven less by faster government review and more by when companies apply for review and the type of drugs they submit.

The study, published in Health Affairs, looked at every new prescription drug approved between 2014 and 2018 in the U.S., and Europe, and then tracked submission delays and review times for these products across regulators in Canada, Japan and Australia through the end of 2022. The analysis assessed the speed of the review process and the timing of submissions for approval, with results broken down by drug characteristics, including therapeutic value of the drugs. 

Specifically, the researchers explored whether different patterns in submission and review times emerged for drugs that offered little added medical benefit over drugs that were already on the market.

“Some commentators have argued that foreign regulators take too long to review drugs and should do more to ensure timely access to new therapies, often pointing to limited availability of new cancer therapies in Europe and other rich markets relative to what’s on the market in the United States, as evidence that regulatory red tape is getting in the way of timely patient access,” said lead author Irene Papanicolas, a professor of health services, policy and practice at the Brown University School of Public Health. “Where we're coming at this from is saying that broader availability of new medicines is generally a great thing — we want patients to get access to new meds — but not all new medications are equally important from a medical standpoint.”

In fact, what stood out most was how companies handled drugs that provide little therapeutic advantage over existing treatments, which the authors referred to as “low-value” drugs in their analysis. The researchers found these drugs were typically submitted to U.S. regulators months or even years before companies sought approval in other high-income countries, giving Americans earlier and wider access to expensive drugs that may not significantly improve patient outcomes.

The findings likely reflect a mix of business incentives and policy choices, according to the research team which along with Papanicolas and other Brown co-authors Olivier Wouters and Tania Sawaya also includes health policy experts from Vanderbilt University and the London School of Economics and Political Science.

The U.S. is the world’s largest drug market, and manufacturers can generally set prices freely when a drug launches. In contrast, many other countries evaluate how much a new drug improves health compared with existing treatments and use that information to negotiate prices or limit coverage, said Wouters, an associate professor in the Department of Health Services, Policy, and Practice.

“There are many drugs that enter the U.S. market that frankly aren’t much better than what’s already available,” Wouters said. “Companies generally seem to submit these lower-value products for approval  earlier in the United States than in other markets. This may reflect the fact that governments in other countries tend to drive a tougher bargain than U.S. payers, which could influence companies’ decisions about where and when to seek approval.”

The study also showed that drugs offering clear medical benefits over existing treatments tended to reach most high-income countries at roughly the same time. This is because drugmakers typically submit those products for approval simultaneously across the high-income countries the researchers looked at. The Food and Drug Administration was only slightly faster than its counterparts abroad in approving the drugs by a few weeks or a month on average, the researchers said.

“Historically, yes, the U.S. gets more new drugs and gets them faster than other countries but a lot of what is driving this pattern aren’t the drugs that have this meaningful therapeutic gain for patients,” Papanicolas said. “Everybody's getting those important new drugs quickly.”

Overall, the study helps add nuance to the question of why the U.S. spends far more on prescription drugs than other high-income countries without consistently better health outcomes. It also paints a more complicated picture as policymakers debate proposals such as the “most favored nation” approach, to bring down drug spending, which proposes linking U.S. drug prices to those paid in peer countries.

“It's not clear how this is going to work,” Papanicolas said. “How will the US authorities handle products that haven’t yet been marketed abroad? Will the policy affect where and when companies decide to submit drugs abroad? No one really knows yet.”

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Journal

Health Affairs

DOI

10.1377/hlthaff.2025.00595 

Article Title

Review Times For New Drugs And Submission Delays Among The FDA And 4 International Regulators, 2014–22

Article Publication Date

2-Feb-2026

 

What's the ROI on R&D in aging? New simulation tool, silverlingings.bio, explores geroscience's impact on US GDP growth and individual health

American Federation for Aging Research

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New York, NY — The American Federation for Aging Research (AFAR) is pleased to announce the release of silverlinings.bio, an interactive report and simulation tool developed by AFAR Scholar-in-Residence Raiany Romanni-Klein, PhD, with support from AFAR, the Amaranth Foundation, and the Methuselah Foundation.

Dr. Romanni-Klein spent the last two years working with a team of economists from Harvard, the Abundance Institute, and the University of Southern Carolina to develop an interactive simulation tool with returns on investments (ROI) for specific research & development (R&D) advancements in aging science — from slowing ovarian and brain aging to running what is likely to be the first-ever clinical trial with aging as an endpoint. 

At silverlinings.bio, users can input their own timelines and assumptions for specific scientific breakthroughs in aging biology, then see the ROI in terms of US lives saved & GDP growth. Through interactive data and illustrations by acclaimed design firm Pentagram, silverlinings.bio explores a wide range of the economic gains and social returns of advancing geroscience such as: 

• How could small advancements in the science of aging change U.S. GDP and population growth? 
• What would be the economic and demographic value of making 41 the new 40, or 65 the new 60? 
• How many lives could we create or save if we could slow reproductive or brain aging by just 1 year? 
• What would billions of healthier hours be worth to the economy?

For this project, Dr. Romanni-Klein interviewed 102 scientists to map expected timelines for specific advancements in aging science; funding amounts required; and to document research opportunities with low commercial incentives but potential for high social and/or economic returns. Among the scientists and stakeholders who lent insights were AFAR President Tom Rando, MD, PhD; Board members Nir Barzilai, MD, Alex Coville, PhD, and Michael Ringel, JD, PhD; as well as AFAR grantees Anne Brunet, PhD, Kristen Fortney, PhD, Jennifer Garrison, PhD, Vera Gorbunova, PhD, and Matthew Kaeberlein, PhD. AFAR Vincent Cristofalo Rising Star Award in Aging Research recipients Daniel Belsky, PhD, and Jamie Justice, PhD, were also interviewed for this project.     

Dr. Romanni-Klein shares: "My ambition is for silverlinings.bio to serve as a connective tissue between scientists, economists, policymakers, and even taxpayers. Science doesn’t advance in a vacuum, and I’m thrilled to have brought together world-class researchers from across disciplines to think through how to outline, quantify, and communicate progress in aging biology."

Dr. Romanni-Klein's tool and research compliments research on the socioeconomic impact of extending healthspan, often referred to as the longevity dividend, published by AFAR-supported scholars over the past two decades. AFAR Irving S. Wright Award recipient, S. Jay Olshansky, PhD, co-authored the foundational article, "Substantial Health Economic Returns From Delayed Aging May Warrant A New Focus For Medical Research" in Health Affairs in 2013. Along with global economist Andrew J. Scott, DPhil, AFAR grantee David A. Sinclair, AO, PhD, published "The Economic Value of Targeting Aging" in Nature Aging in 2021.

"By delaying or preventing age-related diseases, geroscience fuels economic growth at local, national and global levels by reducing medical costs for people and families and helping people remain in the workforce longer," notes Stephanie Lederman, EdM, AFAR Executive Director. "We must continue to find and fund the most promising aging research today in order for these broad-reaching benefits to be realized in the near future."

Explore silverlinings.bio here.

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About AFAR - The American Federation for Aging Research (AFAR) is a national non-profit organization that supports and advances pioneering biomedical research that is revolutionizing how we live healthier and longer. For more than four decades, AFAR has served as the field’s talent incubator, providing $225,316,000 to 4,539 investigators at premier research institutions to date—and growing. A trusted leader and strategist, AFAR also works with public and private funders to steer high quality grant programs and inter-disciplinary research networks. AFAR-funded researchers are finding that modifying basic cellular processes can delay—or even prevent—many chronic diseases, often at the same time. They are discovering that it is never too late—or too early—to improve health. This groundbreaking science is paving the way for innovative new therapies that promise to improve and extend our quality of life—at any age. Learn more at www.afar.org.