Wednesday, March 26, 2025

 SUSTAINABLE DEVELOPMENT GOAL (SDG)

The Frontiers of Knowledge Award goes to Avelino Corma, John Hartwig and Helmut Schwarz for their foundational work on the catalysts that are enabling a more efficient, sustainable chemistry



The BBVA Foundation Frontiers of Knowledge Award in Basic Sciences recognizes fundamental advances in the catalysis field that have improved efficiency and reduced energy consumption in multiple industrial processes



BBVA Foundation

Avelino Corma, winner of the BBVA Foundation Frontiers of Knowledge Award in Basic Sciences. 

image: 

Avelino Corma, winner of the BBVA Foundation Frontiers of Knowledge Award in Basic Sciences

view more 

Credit: BBVA Foundation.




The BBVA Foundation Frontiers of Knowledge Award in Basic Sciences has gone in this seventeenth edition to Avelino Corma (Institute of Chemical Technology, Universitat Politècnica de València-CSIC, Spain), John F. Hartwig (University of California, Berkeley, United States) and Helmut Schwarz (Technical University of Berlin, Germany) for fundamental advances in the catalysis field, in the words of the committee, that have made it possible to “control and accelerate chemical reactions” and obtain products across multiple industrial processes, thereby “improving efficiency and reducing energy consumption.”

Working independently, the new laureates “have led global thinking in the three main research areas devoted to understanding and applying catalysis, covering the entire spectrum of this fundamental field,” said committee member Hongkun Park, Mark Hyman Jr Professor of Chemistry and Professor of Physics at Harvard University (United States). Their combined output has paved the way for a more efficient, sustainable chemistry.

Corma spearheaded the development of solid catalysts from porous materials and holds more than 100 patents with applications that are now being used to improve the efficiency of chemical processes and cut back on pollutant emissions in the production of fuels, plastics, cosmetics and food.

The metal-based catalysts developed by Hartwig, active in the liquid phase, have been game changers in the manufacture of drug treatments for numerous conditions ranging from leukemia to HIV or depression. And new applications are now being sought for plastic waste recycling.

Schwarz has succeeded in analyzing gas-phase chemical reactions atom by atom, elucidating their function with an unprecedented level of detail, a fundamental advance that has already served to cut back on waste production in industrial processes while opening the door to new catalysis applications in multiple domains.

“Avelino Corma is a researcher who starts from fundamental, basic science, then works outwards to apply his results to social challenges like sustainability. The fact that the committee considers him deserving of an internationally prestigious award like the Frontiers of Knowledge is a testament to his scientific stature. And in truth he fits perfectly with the name of the scheme, because his foremost concern is to move the frontiers of knowledge,” said José Capilla, the Rector of the Universitat Politècnica de València (UPV), who nominated the Valencian researcher.

“They say that science is full of researchers who do good things, but very few who actually do new things. John Hartwig not only does new things but he does so time and time again. He is one of those people who carve out paths the rest can only follow,” said his nominator Pedro J. Pérez, Professor of Inorganic Chemistry at the University of Huelva and Head of the Center for Research in Sustainable Chemistry (CIQSO). “I believe the committee made the right decision in distinguishing him alongside professors Corma and Schwarz. Bringing the three together extends this recognition to the whole field of chemistry, and catalysis in particular.”

“This award is extremely well judged given the importance of catalysis research, which accounts for 90 percent of all chemical industry production processes and 30 percent of the world’s GDP. Helmut Schwarz has done real basic science, but has also proved it experimentally. It is to him we owe the insight of incorporating elements of quantum mechanics into basic knowledge of catalytic reactions,” said Jesús Ugalde, Professor of Physical Chemistry at the University of the Basque Country and a collaborator of Professor Schwarz’s.

Porous materials for the production of greener fuels

Avelino Corma has pioneered the field of heterogeneous catalysis, so called because the catalyst is in a different phase of matter from the agents of the chemical reaction the researcher is seeking to accelerate. In his work, concretely, as he explains it, “the catalyst is a solid and the reactants could be gases or liquids.” In the last 35 years, since co-founding the Institute of Chemical Technology (ITQ) at the Universitat Politècnica de València back in 1990, Corma has led the conception and synthesis of microporous materials that act as solid catalysts, where the reactions unfold inside molecule-sized cavities. “We found that by controlling the size of these cavities and channels, we could select not only what molecules penetrated and therefore reacted, but those whose access and reaction we wanted to avoid,” he explains.

His breakthroughs in this field were described in two papers published in Nature in 1998 and 2006, and a later one published in Science in 2017, where he demonstrated the potential of these microporous materials to efficiently accelerate and control chemical reactions, opening the door to a more sustainable, less polluting chemistry. “In these studies, we showed that by controlling the cavities in these solid catalysts, we could control the reactions that ensued. So we could, for instance, reduce their acidity and thus achieve a lower environmental impact.”

Corma’s influence, as the committee remarked, stretches even further than these basic research findings, which have had a major international impact in the catalysis field. He is also the inventor of over 100 patents with industrial applications that are now being rolled out to improve efficiency and sustainability in the production of fuels, plastics, cosmetics and food. For example, “more than 22 plants around the world now produce gasoline more efficiently, with greater energy efficiency, thanks to a catalyst developed in my research.” In addition, many industrial chemical processes are starting to replace fossil fuels with biomass – obtained, for example, from municipal, agricultural or forestry organic waste – through reactions achieved with solid catalysts derived from advances led by Corma. “We are making great strides towards a more sustainable chemistry thanks to this technology, with catalysts that allow us to reduce the use of fossil hydrocarbons and also prevent the release of pollutants through vehicle combustion and factory chimneys.”

For the laureate, moreover, this is just the start of a technological revolution that in coming years could be a powerful transformative tool in the fight against climate change: “I believe catalysts will enable us to capture CO2 from the atmosphere or biomass on the way to developing fuels and chemical processes with far less environmental impact.”

Catalysts to produce medicines against cancer, HIV and hepatitis

The metal-based catalysts developed by John Hartwig have changed the way drugs are manufactured for conditions ranging from leukemia to HIV or depression. He has excelled in the development of homogeneous catalysis, in which both the catalyst and the molecules undergoing the chemical reaction are in the liquid phase, dissolved in a solution. This enables reactions to occur at relatively low temperatures and at very precise sites within the molecule. “There’s a whole series of medicines approved by the Food and Drug Administration (FDA) for diseases like hepatitis C, HIV, depression, psoriasis and leukemia, that rely on the availability of molecules created from reactions developed in my lab,” the new laureate explains.

Hartwig has spent much of his career working on organometallic catalysts, formed by molecules containing both an organic carbon fragment and a transition metal such as platinum. It is precisely the metal-carbon bond that supports chemical reactions by providing a platform on which they can occur.

The awardee has also modified certain enzymes – which, within biological organisms, act as catalysts – by exchanging the naturally occurring metal for another, in order to change their reactivity. Recently, Hartwig was able to insert these “bionic enzymes” into a microorganism and have it make the reagents, the chemicals that react with that enzyme. The chemical reaction, in other words, takes place inside the cells, creating artificial products through a biosynthetic pathway.

Among the reactions Hartwig has focused on most are those occurring at the site of carbon-hydrogen bond cleavage. “These are very strong bonds that are mostly unreactive,” explains the Berkeley chemist, who has developed catalysts that can help break the bond so it accommodates the desired chemical reaction. These catalysts have already been put to work in the production of a key compound for anti-cancer pharmaceuticals and another two against HIV. “It’s really exciting to watch things progress from the very, very fundamental discovery of cleaving a carbon-hydrogen bond to being able to develop large-scale reactions, with thousands of pounds of molecules.”

Another of the awardee’s lauded contributions concerns the formation of the carbon-nitrogen bond; “a reaction – he explains – that doesn’t occur in the absence of a catalyst.” The catalyst he and his team developed to create this bond has led to drugs for depression, HIV and hepatitis C.

Hartwig has since turned his attention to the polymers making up the plastics we use daily, trying to deconstruct their bonds and isolate their components so that they can serve to make new plastic. “Right now plastic is recycled mechanically,” he points out, “but this new method would be chemical recycling, perhaps a future solution to manage the huge amount of plastic waste we generate.”

“The smallest test tube in the world” to observe chemical reactions atom by atom

“My contribution is in many ways unusual,” remarks Helmut Schwarz, “because I have been concerned mainly with basic research but have employed quite unorthodox techniques.” The combination of advanced experiment with advanced computational tools has allowed him to elucidate the functioning of chemical reactions atom by atom, with an unprecedented level of detail. “In most cases there are millions of atoms involved in bringing about a reaction. But what we need to know is which of them are actually doing the business – the aristocratic atoms as we call them.”

Methane, for instance, is known for being very unreactive, but why it is so difficult to activate remains among the big unanswered questions in chemistry. “Millions of tons of methane are released into the atmosphere yearly, and it is a major greenhouse gas. So the question is, can’t we find a better use for it?” The key would lie in finding a way to selectively cleave the carbon-hydrogen bond, a fundamental problem in chemistry which Schwarz set out to probe using the instruments of catalysis.

“Conventional catalysis research is usually done in the condensed phase. But we decided to run our experiment in the gas phase, to avoid uncontrolled side effects that might influence the outcome,” the awardee recalls. They accordingly isolated the atoms one at a time, controlling the reaction environment in such a way that each result could be traced to a single atom rather than the collective effort of thousands – “something people thought for decades was impossible to achieve.”

The means to isolate atoms to observe their individual behavior was provided by the mass spectrometer, a tool invented over 100 years ago but never before used for this purpose. “The mass spectrometer gives us a microscopic view of details which is not available when you look at the average behavior of millions of atoms. It is the world’s smallest test tube.”

Despite his basic science approach, Schwarz’s discoveries have ended up transforming major industrial processes. A case in point is the German factory Degussa, a precious metal refinery that produces a hydrogen, carbon and nitrogen compound used in a large number of industrial applications. The factory developed a way to produce the compound, coupling methane with ammonia by means of a catalyst. But the coal by-product fouled the catalyst and eventually deactivated it. Schwarz was able to uncover key details of how the reaction worked and propose a modification to the catalyst to prevent soot from forming. “So there we have a practical example of how basic research ended up helping a company to substantially improve a process,” says Schwarz.

Having had the experience of his research being dismissed by the more orthodox currents in academia, the awardee’s advice to the new generations is: “Don’t give up too early. Spot where the truly challenging problems are and have the courage to tackle them. Above all, try to excite your co-workers to join the field and see what can be achieved with an enthusiasm for basic research.”

Laureate bio notes

Avelino Corma (Moncófar, Castellón, Spain, 1951) earned a BSc in Chemistry from the University of Valencia in 1973, and just three years later completed his doctorate at the Complutense University of Madrid (UCM). He began his professional career as a scientific researcher for the Spanish National Research Council (CSIC) and is currently a Research Professor at the Institute of Chemical Technology (CSIC/UPV), a mixed center which he co-founded in 1990. For the last fifty years he has researched in heterogeneous catalysis. Author of more than 1,400 papers in international journals, he has also written three books and numerous reviews and served on the editorial boards of leading titles in the catalysis field. Corma holds over 200 invention patents, over 20 of them applied industrially in commercial processes.


John Hartwig,, winner of the BBVA Foundation Frontiers of Knowledge Award in Basic Sciences

John Hartwig (Elmhurst, Illinois, United States, 1964) completed a degree in chemistry at Princeton University, then went on to earn a PhD from the University of California, Berkeley in 1990. That same year he began a postdoctoral fellowship for the American Cancer Society at the Massachusetts Institute of Technology. He moved to Yale University in 1992, rising through the ranks to become Professor of Chemistry and finally Irénée DuPont Chair in Chemistry. In 2006, he joined the faculty at the University of Illinois-Champaign, where he was Kenneth L. Rinehart Jr. Professor of Chemistry until 2011. He then returned to U.C. Berkeley, where he is currently Henry Rapoport Professor of Chemistry. The author of over 400 papers, he has also garnered more than 98,000 citations, holds more than 20 patents and in 2010 published the book Organotransition Metal Chemistry – From Bonding to Catalysis.


Helmut Schwarz, winner of the BBVA Foundation Frontiers of Knowledge Award in Basic Sciences.

Helmut Schwarz (Nickenich, Rhineland-Palatinate, Germany, 1943) graduated in chemistry in 1971 after working in industry. He received his PhD degree a year later from the Technical University of Berlin (Germany), which would become his academic home and where he was appointed Professor of Chemistry in 1978. A member of the German Academy of Natural Sciences Leopoldina, serving as its president from 2010 to 2015, the Academia Europaea, and the Göttingen Academy of Sciences, among others, Schwarz was also a co-founder of the Berlin-Brandeburg Academy of Sciences, where he was vice-president from 1998 to 2003. He holds honorary doctorates from several universities, including the Israel Institute of Technology, the University of Innsbruck and ETH Zurich. As well as authoring over 1,000 papers, he has participated in over 1,000 conferences and served on the editorial boards of various journals. From 2001 to 2007 he was vice-president of the German Research Foundation (DFG).

Nominators

A total of 94 nominations were received in this edition. The awardee researchers were nominated by José E. Capilla, Rector and Professor of Applied Physics at the Universitat Politècnica de València (UPV) (Spain); Pedro J. Pérez, Professor of Inorganic Chemistry at the University of Huelva (Spain); and Geraldine Rauch, President and Professor of Medical Biometry at the Technical University of Berlin (Germany).

Basic Sciences committee and evaluation support panel

The committee in this category was chaired by Theodor Hänsch, Emeritus Director of the Division of Laser Spectroscopy at the Max Planck Institute of Quantum Optics (Germany) and the 2005 Nobel Laureate in Physics, with Aitziber López Cortajarena, Ikerbasque Research Professor, Scientific Director and Biomolecular Nanotechnology Group Leader at CIC biomaGUNE, Center for Cooperative Research in Biomaterials (Spain)acting as secretary.

Remaining members were Emmanuel Candès, Barnum-Simons Professor of Mathematics and Statistics at Stanford University (United States); María José García Borge, Research Professor at the Institute for the Structure of Matter (IEM), CSIC (Spain): Nigel Hitchin, Emeritus Savilian Professor of Geometry in the Mathematical Institute at the University of Oxford (United Kingdom); Hongkun Park, Mark Hyman Jr. Professor of Chemistry and Professor of Physics at Harvard University (United States); Martin Quack, Professor and Head of the Molecular Kinetics and Spectroscopy Group at ETH Zurich (Switzerland); and Sandip Tiwari, Charles N. Mellowes Professor in Engineering, Emeritus at Cornell University (United States) and Distinguished Visiting Professor at the Indian Institute of Technology, Kanpur (India).

The evaluation support panel charged with nominee pre-evaluation was coordinated by Dr. Elena Cartea, Deputy Vice-President of Scientific-Technical Areas at the Spanish National Research Council (CSIC,) and organized into three groups. The Physics Group was coordinated by María José Calderón Prieto, Deputy Coordinator of the Materia Global Area and Scientific Researcher at the Institute of Materials Science of Madrid (ICMM, CSIC) and formed by Alberto Casas González, Research Professor at the Institute for Theoretical Physics (IFT, CSIC-UAM); Pere Colet Rafecas, Research Professor at the Institute for Cross-Disciplinary Physics and Complex Systems (IFISC, CSIC-UIB); Lourdes Fábrega Sánchez, Tenured Scientist at the Institute of Materials Science of Barcelona (ICMAB, CSIC); and Alejandro Luque Estepa, Tenured Scientist at the Institute of Astrophysics of Andalusia (IAA, CSIC). The Chemistry Group was coordinated by José M. Mato, General Director of CIC bioGUNE and CIC biomaGUNE, and formed by Miguel Ángel Bañares González, Research Professor at the Institute of Catalysis and Petrochemistry (ICP, CSIC); Antonio Chica Lara, Coordinator of the Materia Global Area and Scientific Researcher at the Institute of Chemical Technology (ITQ, CSIC-UPV); Jesús Jiménez-Barbero, Scientific Director of CIC bioGUNE and Ikerbasque Research Professor in the Chemical Glycobiology Lab; Gonzalo Jiménez-Osés, Principal Investigator in the Computational Chemistry Lab at CIC bioGUNE; Luis Liz-Marzán, Principal Investigator in the Bionanoplasmonics Lab at CIC biomaGUNE; Aitziber López Cortajarena, Ikerbasque Research Professor, Scientific Director and Principal Investigator in the Biomolecular Nanotechnology Lab at CIC biomaGUNE; and María Luz Sanz Murias, Scientific Researcher at the Institute of General Organic Chemistry (IQOG, CSIC). The Mathematics Group was coordinated by José María Martell Berrocal, CSIC Vice-President for Scientific and Technical Research, and formed by María Jesús Carro Rosell, Professor of Mathematical Analysis at the Complutense University of Madrid (UCM); Alberto Enciso Carrasco, Research Professor at the Institute of Mathematical Sciences (ICMAT, CSIC); Francisco Martín Serrano, Professor of Differential Geometry at the University of Granada; and Rosa María Miró Roig, Professor in the Department of Algebra and Geometry at the University of Barcelona.

About the BBVA Foundation Frontiers of Knowledge Awards

The BBVA Foundation centers its activity on the promotion of world-class scientific research and cultural creation, and the recognition of talent.

The BBVA Foundation Frontiers of Knowledge Awards, funded with 400,000 euros in each of their eight categories, recognize and reward contributions of singular impact in basic sciences, biomedicine, environmental sciences and climate change, information and communication technologies, social sciences, economics, humanities and music. The goal of the awards, established in 2008, is to celebrate and promote the value of knowledge as a global public good, the best instrument to confront the great challenges of our time and expand individual worldviews. Their eight categories are congruent with the knowledge map of the 21st century.

The BBVA Foundation is partnered in these awards by the Spanish National Research Council (CSIC), the country’s premier public research organization. CSIC appoints evaluation support panels made up of leading experts in the corresponding knowledge area, who are charged with undertaking an initial assessment of candidates and drawing up a reasoned shortlist for the consideration of the award committees. CSIC is also responsible for designating each committee’s chair across the eight prize categories and participates in the selection of remaining members, helping to ensure objectivity in the recognition of innovation and scientific excellence. The presidency of CSIC also has a prominent role in the awards ceremony held each year in Bilbao, the permanent home of the BBVA Foundation Frontiers of Knowledge Awards.


 

Basketball analytics investment is key to NBA wins and other successes



Investment in analytics may also benefit college teams and fields beyond sports, a new study shows



Massachusetts Institute of Technology

NBA Analytics 

image: 

MIT scientists quantified the impact of various factors on winning one additional game in a team’s regular season, according to the model based on historical NBA data.

view more 

Credit: Courtesy of Henry Wang, Anette "Peko" Hosoi, et al



If you filled out a March Madness bracket this month, you probably faced the same question with each college match-up: What gives one team an edge over another? Is it a team’s record through the regular season? Or the chemistry among its players? Maybe it’s the experience of its coaching staff or the buzz around a top scorer. 

All of these factors play some role in a team’s chance to advance. But according to a new study by MIT researchers, there’s one member who consistently boosts their team’s performance: the data analyst. 

The new study, which was published this month in the Journal of Sports Economics, quantifies the influence of basketball analytics investment on team performance. The study’s authors looked in particular at professional basketball and compared the  investment in data analytics on each NBA team with the team’s record of wins over 12 seasons. They found that indeed, teams that hired more analytics staff, and invested more in data analysis in general, tended to win more games. 

Analytics department headcount had a positive and statistically significant effect on team wins even when accounting for other factors such as a team’s roster salary, the experience and chemistry among its players, the consistency of its coaching staff, and player injuries through each season. Even with all of these influences, the researchers found that the depth of a team’s data analytics bench, so to speak, was a consistent predictor of the team’s wins. 

What’s more, they were able to quantify basketball analytics’ value, based on their impact on team wins. They found that for every four-fifths of one data analyst, a team gains one additional win in a season. Interestingly, a team can also gain one additional win by increasing its roster salary by $9.6 million. One way to read this is that one data analyst’s impact is worth at least $9 million. 

“I don’t know of any analyst who’s being paid $9 million,” says study author Henry Wang, a graduate student in the MIT Sports Lab. “There is still a gap between how the player is being valued and how the analytics are being valued."

While the study focuses on professional basketball, the researchers say the findings are relevant beyond the NBA. They speculate that college teams that make use of data analytics may have an edge over those who don’t. (Take note, March Madness fans.) And the same likely goes for sports in general, along with any competitive field. 

“This paper hits nicely not just in sports but beyond, with this question of: What is the tangible impact of big data analytics?” says co-author Arnab Sarker PhD ’25, a recent doctoral graduate of MIT’s Institute for Data, Systems and Society (IDSS). “Sports are a really nice, controlled place for analytics. But we’re also curious to what extent we can see these effects in general organizational performance.”

The study is also co-authored by Anette “Peko” Hosoi, the Pappalardo Professor of Mechanical Engineering at MIT. 

Data return

Across the sports world, data analysts have grown in number and scope over the years. Sports analytics’ role in using data and stats to improve team performance was popularized in 2011 with the movie “Moneyball,” based on the 2003 book “Moneyball: The Art of Winning an Unfair Game” by Michael Lewis, who chronicled the 2002 Oakland Athletics and general manager Billy Beane’s use of baseball analytics to win games against wealthier Major League Baseball teams. 

Since then, data analysis has expanded to many other sports, in an effort to make use of the varied and fast-paced sources of data, measurements, and statistics available today. In basketball, analysts can take on many roles, using data, for instance, to optimize a player’s health and minimize injury risk, and to predict a player’s performance to inform draft selection, free agency acquisition, and contract negotiations. 

A data analyst’s work can also influence in-game strategy. Case in point: Over the last decade, NBA teams have strategically chosen to shift to shooting longer-range three-pointers, since Philadelphia 76ers President of Basketball Operations Daryl Morey SM ’00 determined that statistically, shooting more three-pointers wins more games. Today, each of the 30 NBA teams employs at least one basketball analytics staffer. And yet, while a data analyst’s job is entirely based on data, there is not much data on the impact of analysts themselves. 

“Teams and leagues are spending millions of dollars on embracing analytical tools without a real sense of return-on-investment,” Wang notes. 

Numbers value

The MIT researchers aimed in their new study to quantify the influence of NBA team analysts, specifically on winning games. To do so, they looked to major sources of sports data such as ESPN.com, and NBAstuffer.com, a website that hosts a huge amount of stats on NBA games and team stats, including hired basketball analytics staff, that the website’s managers compile based on publicly available data, such as from official team press releases and staff directories, as well as LinkedIn and X profiles, and news and industry reports.

For their new study, Wang and his colleagues gathered data on each of the 30 NBA teams, over a period from 2009 to 2023, 2009 being the year that NBAstuffer.com started compiling team data. For every team in each season during this period, the researchers recorded an “analyst headcount,” meaning the number of basketball operations analytics staff employed by a team. They considered an analyst to be data analysts, software engineers,  sports scientists, directors of research, and other technical positions by title, but also staff members who aren’t formally analysts but may be known to be particularly active in the basketball analytics community. In general, they found that in 2009, a total of 10 data analysts were working across the NBA. In 2023, that number ballooned to 132, with some teams employing more analysts than others. 

“What we’re trying to measure is a team’s level of investment in basketball analytics,” Wang explains. “The best measure would be if every team told us exactly how much money they spent every year on their R&D and data infrastructure and analysts. But they’re not going to do that. So headcount is the next best thing.”

In addition to analytics headcount, the researchers also compiled data on other win-influencing variables, such as roster salary (Does a higher-paid team win more games?), roster experience (Does a team with more veterans win more games?), consistent coaching (Did a new coach shake up a team’s win record?) and season injuries (How did a team’s injuries affect its wins?). The researchers also noted “road back-to-backs,” or the number of times a team had to play consecutive away games (Does the wear and tear of constant travel impact wins?). 

The researchers plugged all this data into a “two-way fixed effects” model to estimate the relative effect that each variable has on the number of additional games a team can win in a season. 

“The model learns all these effects, so we can see, for instance, the tradeoff between analyst and roster salary when contributing to win total,” Wang explains.

Their finding that teams with a higher analytics headcount tended to win more games wasn’t entirely surprising.

“We’re still at a point where the analyst is undervalued,” Wang says. “There probably is a sweet spot, in terms of headcount and wins. You can’t hire 100 analysts and expect to go in 82-and-0 next season. But right now a lot of teams are still below that sweet spot, and this competitive advantage that analytics offers has yet to be fully harvested.” 

###

Written by Jennifer Chu, MIT News

 

How Zika virus knocks out our immune defenses



LJI and UC San Diego scientists make striking discovery as they work to combat Zika and related viral threats




La Jolla Institute for Immunology

LJI Professor Sujan Shresta, Ph.D. 

image: 

Sujan Shresta, Ph.D., Professor at La Jolla Institute for Immunology

view more 

Credit: La Jolla Institute for Immunology




LA JOLLA, CA—Zika virus and dengue virus are very close relatives. Both are mosquito-borne flaviviruses, and both specialize in infecting a host's dendritic cells.

But a new Nature Communications study, led by scientists at La Jolla Institute for Immunology (LJI) and UC San Diego shows that these two viruses have vastly different ways of making us sick. 

Zika virus uses stealth. Zika virus slips into dendritic cells and blocks the dendritic cells from alerting nearby T cells to danger. It's the classic horror movie cliche—the creeper is already in the house, and the phone lines have been cut.

Dengue virus prefers shock-and-awe. Dengue virus pushes dendritic cells to churn out molecules called pro-inflammatory cytokines, which send the immune system into overdrive. The virus spreads to new host cells as the body grapples with this overwhelming immune response.

Understanding these different infection strategies is key for developing life-saving vaccines, says LJI Professor Sujan Shresta, Ph.D. Her team is working to develop vaccines that harness virus-fighting T cells to combat Zika virus, dengue virus, and other flaviviruses with pandemic potential.

"Our ultimate goal is to develop vaccines against these very difficult viruses," says Shresta, who co-led the new study with UC San Diego Professor Aaron Carlin, M.D., Ph.D. "Understanding how these viruses manipulate the immune response can help guide the development of the best vaccine approach."

Why Zika-infected dendritic cells can't call for help

This new collaboration is the first to show exactly how Zika virus accomplishes its sneak attack. Using a technique pioneered by Carlin during his postdoctoral work at UC San Diego and LJI, the researchers isolated only Zika- or dengue-infected dendritic cells derived from human blood samples. Then they examined gene expression in these cells to see how they responded to the infection.

The Zika-infected dendritic cells did very little—and the researchers could finally see why. They found that Zika virus actively suppresses an important molecule in cells, called NF-κB p65. Without NF-κB p65, dendritic cells get stuck in an immature state and cannot promote T cells to fight the infection.

In contrast, dengue virus really stimulates dendritic cells to make lots of pro-inflammatory cytokines and respond aggressively to the presence of the virus.

This discovery helps explain why many people develop a weaker immune response to Zika virus versus dengue virus, says Ying-Ting Wang, Ph.D, former LJI postdoctoral fellow and first author of the current study. The new research also provides a clue to how Zika virus manages to break past immune defenses in the placenta to infect developing fetuses.

"Zika virus inhibits any kind of productive dendritic cell response," says Carlin. "We think that's a key to its pathogenesis, its ability to spread silently and persist within humans that it infects."

Right now, there are no effective vaccines or therapeutics against Zika virus or dengue virus. The new findings may help scientists outsmart these viruses. 

"Looking at these human cell cultures helps us understand what's going on in people," says Shresta. "Our findings inform how we might develop vaccines and antivirals that manipulate these cellular pathways."

Why Zika and dengue vaccines are critical

Shresta and Carlin are eager to move forward with flavivirus research. They know there's no time to lose.

Many mosquito-borne viruses are spreading rapidly as disease-carrying Aedes mosquitoes expand into new habitats. In fact, last year was the worst on record for reported dengue virus cases. Dengue virus infected between 100 million and 400 million people in 2024, according to the World Health Organization (WHO). These cases included the first-ever cases of locally transmitted dengue virus infection in San Diego County.

Many flaviviruses also have pandemic potential. In a 2024 report, WHO listed Zika virus, dengue virus, West Nile virus, tick-borne encephalitis virus, and yellow fever virus among the top pathogens for research “prioritization” in preparation for the next pandemic.

Shresta has monitored the spread of these viruses in recent years. As she explains, many of these viruses overlap in the same regions. As a result, millions of people are at risk of infection from a variety of flaviviruses that attack dendritic cells from different angles.

Shresta is leading efforts at LJI to develop a "pan-flavivirus" vaccine that might combat many flaviviruses at once. "Our challenge is to develop vaccines that are both safe and effective against not just one virus, but all these closely related flaviviruses," says Shresta.

At the same time, Carlin is looking to develop antivirals that might interfere with Zika's ability to suppress NF-κB p65. He'd also like to investigate exactly how dengue virus over-stimulates the immune system. 

"Understanding how dengue virus stimulates that shock-like phenotype in people would allow for precision guided therapies that prevent death and hospitalization without inhibiting our immune system’s ability to clear the virus," says Carlin.

Additional authors of the study, "Zika but not Dengue Virus Infection Limits NF-κB Activity in Human Monocyte-Derived Dendritic Cells and Suppresses their Ability to Activate T Cells," included Ying-Ting Wang, Emilie Branche, Jialei Xie, Rachel E. McMillan, Fernanda Ana-Sosa-Batiz, Hsueh-Han Lu, Qin Hui Li, Alex E. Clark, Joan M. Valls Cuevas, Karla M. Viramontes, Aaron F. Garretson, Rubens Prince dos Santos Alves, Sven Heinz, and Christopher Benner.

This study was supported by a Career Award for Medical Scientists from the Burroughs Wellcome Fund, a fellowship from the Ministry of Science and Technology of Taiwan (108-2917-I-564-032), an American Association of Immunologists Career Reentry Fellowship, and the National Institutes of Health (grants K08 AI130381, R01 AI116813, R01 AI153500, and R01 AI163188.)

DOI: 10.1038/s41467-025-57977-2