Think fast — or not: Mathematics behind decision making

New research from a Florida State University professor and colleagues explains the mathematics behind how initial predispositions and additional information affect decision making.

The research team’s findings show that when decision makers quickly come to a conclusion, the decision is more influenced by their initial bias, or a tendency to err on the side of one of the choices presented. If decision makers wait to gather more information, the slower decision will be less biased. The work was published today in Physical Review E.

“The basic result might seem sort of intuitive, but the mathematics we had to employ to prove this was really non-trivial,” said co-author Bhargav Karamched, an assistant professor in the FSU Department of Mathematics and the Institute of Molecular Biophysics. “We saw that for the first decider in a group, the trajectory of their belief is almost a straight line. The last decider hovers around, going back and forth for a while before making a decision. Even though the underlying equation for each agent’s belief is the same except for their initial bias, the statistics and behavior of each individual is very different.”

The researchers built a mathematical model that represented a group of agents required to decide between two conclusions, one which was correct and one which was incorrect. The model assumed each actor within a group was acting rationally, that is, deciding based off their initial bias and the information they are presented, rather than being swayed by the decisions of individuals around them.

Even with evidence and assuming perfect rationality, bias toward a particular decision caused the earliest deciders in the model to make the wrong conclusion 50% of the time. The more information actors gathered, the more likely they were to behave as if they weren’t biased and to arrive at a correct conclusion.

Of course, in the real world, people are swayed by all sorts of inputs, such as their emotions, the decisions their friends made and other variables. This research offers a metric showing how individuals within a group should make decisions if they are acting rationally. Future research could compare real-world data against this metric to see where people are diverting from optimally rational choices and consider what might have caused their divergence.

The researchers’ model is known as a drift diffusion model, so called because it combines two concepts: individual actor’s tendency to “drift,” or move toward an outcome based on evidence, and the random “diffusion,” or variability of the information presented.

The work could be used, for example, to understand when people are being unduly swayed by early decisions or falling victim to groupthink. It even helps describe other complex scenarios with many individual actors, such as the immune system or the behavior of neurons.

“There is still a lot of work to do to understand decision making in more complicated situations, such as cases where more than two alternatives are presented as choices, but this is a good starting point,” Karamched said.

This research was a multi-institution collaboration involving doctoral candidate Samantha Linn and Associate Professor Sean D. Lawley of the University of Utah, Associate Professor Zachary P. Kilpatrick of the University of Colorado, and Professor Krešimir Josic of the University of Houston.

This research was supported by the National Science Foundation and the National Institutes of Health.

Share Button

Girl died drinking Costa hot chocolate, inquest told

The 13-year-old had a dairy allergy went into anaphylactic shock, an inquest hears

Share Button

New vaccine for respiratory disease rolls out in Scotland

The vaccination programme is aimed at protecting newborn babies and older adults against a dangerous disease.

Share Button

Doctor warned Nottingham attacker could kill

The concern that Valdo Calocane could “end up killing someone” appears in a summary of medical records shared with BBC Panorama.

Share Button

The threat of mpox has returned, but public knowledge about it has declined

It has been two years since the World Health Organization declared a global health emergency over an outbreak of mpox, a disease endemic to Africa that had spread to scores of countries. Now, in the summer of 2024, a deadlier version of the infectious disease has spread from the Democratic Republic of Congo to other African nations, the strain that originally hit the United States has shown signs of a resurgence, and this week the Centers for Disease Control and Prevention (CDC) issued a new alert on mpox to health care providers.

But while the American public quickly learned about the disease during the summer of 2022, as the number of cases declined and media attention waned, much of that knowledge appears to have been lost, according to new survey data from the Annenberg Public Policy Center of the University of Pennsylvania.

In a nationally representative survey of about 1,500 U.S. empaneled adults conducted in July 2024, the policy center finds that knowledge about mpox — which increased from July to August 2022 — has declined, along with fear of the disease (which was previously called monkeypox). This wave of the Annenberg Science and Public Health (ASAPH) knowledge survey finds that:

  • Only 1 in 20 Americans (5%) are worried about contracting mpox in the next three months, down from 21% in August 2022. In addition, fewer than 1 in 10 (9%) are worried that they or their families will contract mpox.
  • Fewer than 1 in 5 people (17%) know that mpox is less contagious than Covid-19, down from 41% in August 2022. Nearly two-thirds (63%) are not sure.
  • Just a third of people (34%) know that men who have sex with men are at a higher risk of infection with mpox, down from nearly two-thirds (63%) in August 2022.
  • Less than half (45%) know that a vaccine for mpox exists, down from 61% in August 2022.
  • Fewer people (58%) know that it’s false to say that getting a Covid-19 vaccine increases your chances of getting mpox, down from 71%.

“The speed with which the public learned needed information about mpox in the summer of 2022 was a tribute to effective communication by the public health community,” said Kathleen Hall Jamieson, director of the Annenberg Public Policy Center (APPC) and director of the survey. “That same expertise should now be deployed to ensure that those at risk remember mpox’s symptoms, modes of transmission, and the protective power of vaccination.”

Mpox outbreaks in 2024 and 2022

Discovered in 1958, mpox is a rare disease caused by an orthopox virus, and is a less deadly member of the family of viruses that cause smallpox, according to the CDC. Mpox may cause fever, chills, headaches, muscle aches, swollen lymph nodes, and painful rashes, particularly on the hands, feet, face, chest, mouth, or near the genitals. According to the CDC, the disease can spread through contact with infected wild animals, close (including sexual) contact with an infected individual, including contact with scabs or body fluids, or contact with contaminated materials such as towels or bedding.

The current outbreak involves an mpox strain known as clade I, which is especially virulent and dangerous to infants and children under the age of 5, according to the World Health Organization (WHO), whose director general announced this week that he was convening a panel of experts to advise him whether the outbreak should be declared a global health emergency. (The WHO called an end to the 2022 mpox global health emergency in May 2023.) The WHO says there have been over 14,000 cases this year, with at least 511 deaths, according to STAT News. In the Democratic Republic of Congo (DRC), 62% of the deaths involved children under age 5. The current subtype appears to be spread through routine close contact between individuals, though in November 2023 the WHO confirmed that this strain was also being sexually transmitted.

This deadlier strain of monkeypox has not been reported outside central and east Africa, the CDC said.

A different strain of mpox in the 2022 outbreak, known as the clade II subtype, which spread across the United States, was less deadly and largely transmitted through sexual contact, and men who have sex with men were at higher risk of the disease. That earlier strain never disappeared entirely, though new cases are at a much lower level, according to the CDC. The majority of cases are in people who are not vaccinated against mpox or have received only one of the two recommended doses, the CDC reported.

Vaccination against mpox

While knowledge concerning mpox has declined significantly, there has been a less pronounced drop in people’s intentions to get vaccinated against the disease. The CDC has urged individuals to be vaccinated with two doses of the vaccine Jynneos four weeks apart — both for people who have been exposed to mpox virus to help prevent its spread and for people with risk factors for mpox, including men who have sex with men.

An earlier APPC survey, in October 2022, found that 76% of respondents said they were “very likely” or “somewhat likely” to get an mpox vaccine if they were exposed to mpox. The current survey, in July 2024, found a slight decline — 70% of respondents reported that they were either very/somewhat likely to get the vaccine (68%) or were already vaccinated against mpox (2%). However, 3 in 10 (30%) said they were “not too likely” or “not at all likely” to get vaccinated against mpox if exposed to the virus. In addition, 70% reported in July 2024 that they thought the benefits of vaccination against mpox outweighed the risks.

APPC’s ASAPH survey

The survey data come from the 20th wave of a nationally representative panel of 1,496 U.S. adults, first empaneled in April 2021, conducted for the Annenberg Public Policy Center by SSRS, an independent market research company. This wave of the Annenberg Science and Public Health Knowledge (ASAPH) survey was fielded July 11-18, 2024, and has a margin of sampling error (MOE) of ± 3.6 percentage points at the 95% confidence level. All figures are rounded to the nearest whole number and may not add to 100%.

Share Button

A new mechanism for shaping animal tissues

A key question that remains in biology and biophysics is how three-dimensional tissue shapes emerge during animal development. Research teams from the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany, the Excellence Cluster Physics of Life (PoL) at the TU Dresden, and the Center for Systems Biology Dresden (CSBD) have now found a mechanism by which tissues can be “programmed” to transition from a flat state to a three-dimensional shape. To accomplish this, the researchers looked at the development of the fruit fly Drosophila and its wing disc pouch, which transitions from a shallow dome shape to a curved fold and later becomes the wing of an adult fly.

The researchers developed a method to measure three-dimensional shape changes and analyze how cells behave during this process. Using a physical model based on shape-programming, they found that the movements and rearrangements of cells play a key role in shaping the tissue. This study, published in Science Advances, shows that the shape programming method could be a common way to show how tissues form in animals.

Epithelial tissues are layers of tightly connected cells and make up the basic structure of many organs. To create functional organs, tissues change their shape in three dimensions. While some mechanisms for three-dimensional shapes have been explored, they are not sufficient to explain the diversity of animal tissue forms. For example, during a process in the development of a fruit fly called wing disc eversion, the wing transitions from a single layer of cells to a double layer. How the wing disc pouch undergoes this shape change from a radially symmetric dome into a curved fold shape is unknown.

The research groups of Carl Modes, group leader at the MPI-CBG and the CSBD, and Natalie Dye, group leader at PoL and previously affiliated with MPI-CBG, wanted to find out how this shape change occurs. “To explain this process, we drew inspiration from “shape-programmable” inanimate material sheets, such as thin hydrogels, that can transform into three-dimensional shapes through internal stresses when stimulated,” explains Natalie Dye, and continues: “These materials can change their internal structure across the sheet in a controlled way to create specific three-dimensional shapes. This concept has already helped us understand how plants grow. Animal tissues, however, are more dynamic, with cells that change shape, size, and position.”

To see if shape programming could be a mechanism to understand animal development, the researchers measured tissue shape changes and cell behaviors during the Drosophila wing disc eversion, when the dome shape transforms into a curved fold shape. “Using a physical model, we showed that collective, programmed cell behaviors are sufficient to create the shape changes seen in the wing disc pouch. This means that external forces from surrounding tissues are not needed, and cell rearrangements are the main driver of pouch shape change,” says Jana Fuhrmann, a postdoctoral fellow in the research group of Natalie Dye. To confirm that rearranged cells are the main reason for pouch eversion, the researchers tested this by reducing cell movement, which in turn caused problems with the tissue shaping process.

Abhijeet Krishna, a doctoral student in the group of Carl Modes at the time of the study, explains: “The new models for shape programmability that we developed are connected to different types of cell behaviors. These models include both uniform and direction-dependent effects. While there were previous models for shape programmability, they only looked at one type of effect at a time. Our models combine both types of effects and link them directly to cell behaviors.”

Natalie Dye and Carl Modes conclude: “We discovered that internal stress brought on by active cell behaviors is what shapes the Drosophila wing disc pouch during eversion. Using our new method and a theoretical framework derived from shape-programmable materials, we were able to measure cell patterns on any tissue surface. These tools help us understand how animal tissue transforms their shape and size in three dimensions. Overall, our work suggests that early mechanical signals help organize how cells behave, which later leads to changes in tissue shape. Our work illustrates principles that could be used more widely to better understand other tissue-shaping processes.”

Share Button

As temperatures break records, many are unaware of symptoms of heat-related illnesses

With NASA data showing that July 22, 2024, was the hottest day on record and indications that July may have been the hottest month, an Annenberg Public Policy Center survey conducted in mid-July found that most people know three of the symptoms of a heat-related illness but do not know the location of their nearest cooling center. At the same time, increasing numbers of people think that heat waves are becoming more frequent and intense and affecting their daily activities.

Knowledge of cooling centers in the case of extreme heat

Although the locations of cooling centers, or indoor air-conditioned facilities such as libraries, community and senior centers, schools are publicized by city governments on hot days, many of those surveyed report being unaware of where to find one. Two-thirds of respondents (67%) say they do not know the location of a cooling center to which they could go to in case of extreme heat, a number statistically unchanged from last November. “Communities must do a better job of making the public, especially the most vulnerable, aware of these centers,” said Ken Winneg, managing director of survey research at APPC.

More today see link between extreme heat and climate change.

When compared with an APPC survey in November 2023, significantly more people now say that climate change is increasing the risk of heat-related illnesses, respiratory diseases, and insect-borne diseases. Two-thirds (67%) hold this view vs. just under 6 in 10 (58%) in November 2023.

More people indicate that heat waves in the United States are becoming more frequent and intense than in the past. About two-thirds (65%) believe heat waves are becoming more frequent and intense. Fifty-eight percent (58%) felt this way in November 2023, when we last asked the question. About a quarter (24%) believe heat waves are about as frequent and intense as they have always been, statistically unchanged from our earlier survey.

At the same time, the proportion of people who say extreme heat has often or frequently affected their typical daily activities in the past year has increased significantly. Forty-three percent (43%) say extreme outdoor heat has often (22%) or frequently (21%) affected their daily activities, an 8-point increase compared with November 2023 (35% in total said either “often” or “frequently”).

Signs of heat-related illnesses

Notably, most people also know three of the telltale signs of heat-related illnesses:

  • Dizziness (89% compared to 86% in August 2022)
  • Nausea (83% compared to 79% in August 2022)
  • Hot, red, dry, or damp skin (72%, statistically unchanged from August 2022)
  • Cold, pale, and clammy skin (42%, statistically unchanged from August 2022).

Public understands some extreme heat risks better than others

Thinking about the next 10 years, just under 6 in 10 (58%) think that people in their community will be more likely to experience heat stroke caused by extreme heat waves. This is significantly higher than in November 2023 when just over half (52%) said they thought people in their community would be more likely to experience heat stroke caused by extreme heat waves in the next 10 years.

However, only 3 in 10 (30%) know that a pregnant person in the U.S. who is exposed to extreme heat is more likely to deliver their baby early than a pregnant person who is not exposed to extreme heat. About a quarter (23%) incorrectly say that a pregnant person in the U.S. is either less or just as likely to deliver a baby early. Forty-seven percent (47%) are unsure which is correct.

Broad awareness that heat-related deaths are most common among seniors

Two-thirds (67%) know that heat-related deaths are most common among older adults, aged 65 or older, slightly but significantly higher than in August 2022 (62%).

Preventing heat-related illnesses

Nearly all (92%) know that drinking water is better to prevent heat-related illnesses than drinking sugary drinks.

APPC’s ASAPH survey

The survey data come from the 20th wave of a nationally representative panel of 1,496 U.S. adults, first empaneled in April 2021, conducted for the Annenberg Public Policy Center by SSRS, an independent market research company. This wave of the Annenberg Science and Public Health Knowledge (ASAPH) survey was fielded July 11-18, 2024, and has a margin of sampling error (MOE) of ± 3.6 percentage points at the 95% confidence level. All figures are rounded to the nearest whole number and may not add to 100%. Combined subcategories may not add to totals in the topline and text due to rounding.

Share Button

Millions of years for plants to recover from global warming

Scientists often seek answers to humanity’s most pressing challenges in nature. When it comes to global warming, geological history offers a unique, long-term perspective. Earth’s geological history is spiked by periods of catastrophic volcanic eruptions that released vast amounts of carbon into the atmosphere and oceans. The increased carbon triggered rapid climate warming that resulted in mass extinctions on land and in marine ecosystems. These periods of volcanism may also have disrupted carbon-climate regulation systems for millions of years.

Ecological imbalance

Earth and environmental scientists at ETH Zurich led an international team of researchers from the University of Arizona, University of Leeds, CNRS Toulouse, and the Swiss Federal Institute for Forest Snow and Landscape Research (WSL) in a study on how vegetation responds and evolves in response to major climatic shifts and how such shifts affect Earth’s natural carbon-climate regulation system.

Drawing on geochemical analyses of isotopes in sediments, the research team compared the data with a specially designed model, which included a representation of vegetation and its role in regulating the geological climate system. They used the model to test how the Earth system responds to the intense release of carbon from volcanic activity in different scenarios. They studied three significant climatic shifts in geological history, including the Siberian Traps event that caused the Permian-Triassic mass extinction about 252 million years ago. ETH Zurich professor, Taras Gerya points out, “The Siberian Traps event released some 40,000 gigatons (Gt) of carbon over 200,000 years. The resulting increase in global average temperatures between 5 — 10°C caused Earth’s most severe extinction event in the geologic record.”

Move, adapt, or perish

“The recovery of vegetation from the Siberian Traps event took several millions of years and during this time Earth’s carbon-climate regulation system would have been weak and inefficient resulting in long-term climate warming,” explains lead author, Julian Rogger, ETH Zurich.

Researchers found that the severity of such events is determined by how fast emitted carbon can be returned to Earth’s interior — sequestered through silicate mineral weathering or organic carbon production, removing carbon from Earth’s atmosphere. They also found that the time it takes for the climate to reach a new state of equilibrium depended on how fast vegetation adapted to increasing temperatures. Some species adapted by evolving and others by migrating geographically to cooler regions. However, some geological events were so catastrophic that plant species simply did not have enough time to migrate or adapt to the sustained increase in temperature. The consequences of which left its geochemical mark on climate evolution for thousands, possibly millions, of years.

Today’s human-induced climate crisis

What does this mean for human induced climate change? The study found that a disruption of vegetation increased the duration and severity of climate warming in the geologic past. In some cases, it may have taken millions of years to reach a new stable climatic equilibrium due to a reduced capacity of vegetation to regulate Earth’s carbon cycle.

“Today, we find ourselves in a major global bioclimatic crisis,” comments Loïc Pellissier, Professor of Ecosystems and Landscape Evolution at ETH Zurich and WSL. “Our study demonstrates the role of a functioning of vegetation to recover from abrupt climatic changes. We are currently releasing greenhouse gases at a faster rate than any previous volcanic event. We are also the primary cause of global deforestation, which strongly reduces the ability of natural ecosystems to regulate the climate. This study, in my perspective, serves as ‘wake-up call’ for the global community.”

Share Button

Potential new approach to enhancing stem-cell transplants

A discovery by a three-member Albert Einstein College of Medicine research team may boost the effectiveness of stem-cell transplants, commonly used for patients with cancer, blood disorders, or autoimmune diseases caused by defective stem cells, which produce all the body’s different blood cells. The findings, made in mice, were published today in the journal Science.

“Our research has the potential to improve the success of stem-cell transplants and expand their use,” explained Ulrich Steidl, M.D., Ph.D., professor and chair of cell biology, interim director of the Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine, and the Edward P. Evans Endowed Professor for Myelodysplastic Syndromes at Einstein, and deputy director of the National Cancer Institute-designated Montefiore Einstein Comprehensive Cancer Center (MECCC).

Dr. Steidl, Einstein’s Britta Will, Ph.D., and Xin Gao, Ph.D., a former Einstein postdoctoral fellow, now at the University of Wisconsin in Madison, are co-corresponding authors on the paper.

Mobilizing Stem Cells

Stem-cell transplants treat diseases in which an individual’s hematopoietic (blood-forming) stem cells (HSCs) have become cancerous (as in in leukemia or myelodysplastic syndromes) or too few in number (as in bone marrow failure and severe autoimmune disorders). The therapy involves infusing healthy HSCs obtained from donors into patients. To harvest those HSCs, donors are given a drug that causes HSCs to mobilize, or escape, from their normal homes in the bone marrow and enter the blood, where HSCs can be separated from other blood cells and then transplanted. However, drugs used to mobilize HSCs often don’t liberate enough of them for the transplant to be effective.

“It’s normal for a tiny fraction of HSCs to exit the bone marrow and enter the blood stream, but what controls this mobilization isn’t well understood,” said Dr. Will, associate professor of oncology and of medicine, and the Diane and Arthur B. Belfer Faculty Scholar in Cancer Research at Einstein, and the co-leader of the Stem Cell and Cancer Biology research program at MECCC. “Our research represents a fundamental advance in our understanding, and points to a new way to improve HSC mobilization for clinical use.”

Tracking Trogocytosis

The researchers suspected that variations in proteins on the surface of HSCs might influence their propensity to exit the bone marrow. In studies involving HSCs isolated from mice, they observed that a large subset of HSCs display surface proteins normally associated with macrophages, a type of immune cell. Moreover, HSCs with these surface proteins largely stayed in the bone marrow, while those without the markers readily exited the marrow when drugs for boosting HSCs mobilization were given.

After mixing HSCs with macrophages, the researchers discovered that some HSCs engaged in trogocytosis, a mechanism whereby one cell type extracts membrane fractions of another cell type and incorporates them into their own membranes. Those HSCs expressing high levels of the protein c-Kit on their surface were able to carry out trogocytosis, causing their membranes to be augmented with macrophage proteins — and making them far more likely than other HSCs to stay in the bone marrow. The findings suggest that impairing c-Kit would prevent trogocytosis, leading to more HSCs being mobilized and made available for transplantation.

“Trogocytosis plays a role in regulating immune responses and other cellular systems, but this is the first time anyone has seen stem cells engage in the process. We are still seeking the exact mechanism for how HSCs regulate trogocytosis,” said Dr. Gao, assistant professor of pathology and laboratory medicine at the University of Wisconsin-Madison, Madison, WI.

The researchers intend to continue their investigation into this process: “Our ongoing efforts will look for other functions of trogocytosis in HSCs, including potential roles in blood regeneration, eliminating defective stem cells and in hematologic malignancies,” added Dr. Will.

The study originated in the laboratory of the late Paul S. Frenette, M.D., a pioneer in hematopoietic stem cell research and founding director of the Ruth L. and David S. Gottesman Institute for Stem Cell Biology and Regenerative Medicine Research at Einstein. Other key contributors include Randall S. Carpenter, Ph.D., and Philip E. Boulais, Ph.D., both postdoctoral scientists at Einstein.

The Science paper is titled, “Regulation of the hematopoietic stem cell pool by c-Kit-associated trogocytosis.” Additional authors are Huihui Li, Ph.D., and Maria Maryanovich, Ph.D., both at Einstein, Christopher R. Marlein, Ph.D., at Einstein and FUJIFILM Diosynth Biotechnologies, Wilton, England, and Dachuan Zhang, Ph.D., at Einstein and Shanghai Jiao Tong University School of Medicine, Shanghai, China, Matthew Smith at the University of Wisconsin-Madison, and David J. Chung, M.D., Ph.D., at Memorial Sloan Kettering Cancer Center, New York, NY.

The study was funded by grants from the National Institutes of Health (U01DK116312, R01DK056638, R01DK112976, R01HL069438, DK10513, CA230756, R01HL157948 and R35CA253127).

Share Button

Largest protein yet discovered builds algal toxins

While seeking to unravel how marine algae create their chemically complex toxins, scientists at UC San Diego’s Scripps Institution of Oceanography have discovered the largest protein yet identified in biology. Uncovering the biological machinery the algae evolved to make its intricate toxin also revealed previously unknown strategies for assembling chemicals, which could unlock the development of new medicines and materials.

Researchers found the protein, which they named PKZILLA-1, while studying how a type of algae called Prymnesium parvum makes its toxin, which is responsible for massive fish kills.

“This is the Mount Everest of proteins,” said Bradley Moore, a marine chemist with joint appointments at Scripps Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences and senior author of a new study detailing the findings. “This expands our sense of what biology is capable of.”

PKZILLA-1 is 25% larger than titin, the previous record holder, which is found in human muscles and can reach 1 micron in length (0.0001 centimeter or 0.00004 inch).

Published today in Science and funded by the National Institutes of Health and the National Science Foundation, the study shows that this giant protein and another super-sized but not record-breaking protein — PKZILLA-2 — are key to producing prymnesin — the big, complex molecule that is the algae’s toxin. In addition to identifying the massive proteins behind prymnesin, the study also uncovered unusually large genes that provide Prymnesium parvum with the blueprint for making the proteins.

Finding the genes that undergird the production of the prymnesin toxin could improve monitoring efforts for harmful algal blooms from this species by facilitating water testing that looks for the genes rather than the toxins themselves.

“Monitoring for the genes instead of the toxin could allow us to catch blooms before they start instead of only being able to identify them once the toxins are circulating,” said Timothy Fallon, a postdoctoral researcher in Moore’s lab at Scripps and co-first author of the paper.

Discovering the PKZILLA-1 and PKZILLA-2 proteins also lays bare the alga’s elaborate cellular assembly line for building the toxins, which have unique and complex chemical structures. This improved understanding of how these toxins are made could prove useful for scientists trying to synthesize new compounds for medical or industrial applications.

“Understanding how nature has evolved its chemical wizardry gives us as scientific practitioners the ability to apply those insights to creating useful products, whether it’s a new anti-cancer drug or a new fabric,” said Moore.

Prymnesium parvum, commonly known as golden algae, is an aquatic single-celled organism found all over the world in both fresh and saltwater. Blooms of golden algae are associated with fish die offs due to its toxin prymnesin, which damages the gills of fish and other water breathing animals. In 2022, a golden algae bloom killed 500-1,000 tons of fish in the Oder River adjoining Poland and Germany. The microorganism can cause havoc in aquaculture systems in places ranging from Texas to Scandinavia.

Prymnesin belongs to a group of toxins called polyketide polyethers that includes brevetoxin B, a major red tide toxin that regularly impacts Florida, and ciguatoxin, which contaminates reef fish across the South Pacific and Caribbean. These toxins are among the largest and most intricate chemicals in all of biology, and researchers have struggled for decades to figure out exactly how microorganisms produce such large, complex molecules.

Beginning in 2019, Moore, Fallon and Vikram Shende, a postdoctoral researcher in Moore’s lab at Scripps and co-first author of the paper, began trying to figure out how golden algae make their toxin prymnesin on a biochemical and genetic level.

The study authors began by sequencing the golden alga’s genome and looking for the genes involved in producing prymnesin. Traditional methods of searching the genome didn’t yield results, so the team pivoted to alternate methods of genetic sleuthing that were more adept at finding super long genes.

“We were able to locate the genes, and it turned out that to make giant toxic molecules this alga uses giant genes,” said Shende.

With the PKZILLA-1 and PKZILLA-2 genes located, the team needed to investigate what the genes made to tie them to the production of the toxin. Fallon said the team was able to read the genes’ coding regions like sheet music and translate them into the sequence of amino acids that formed the protein.

When the researchers completed this assembly of the PKZILLA proteins they were astonished at their size. The PKZILLA-1 protein tallied a record-breaking mass of 4.7 megadaltons, while PKZILLA-2 was also extremely large at 3.2 megadaltons. Titin, the previous record-holder, can be up to 3.7 megadaltons — about 90-times larger than a typical protein.

After additional tests showed that golden algae actually produce these giant proteins in life, the team sought to find out if the proteins were involved in making the toxin prymnesin. The PKZILLA proteins are technically enzymes, meaning they kick off chemical reactions, and the team played out the lengthy sequence of 239 chemical reactions entailed by the two enzymes with pens and notepads.

“The end result matched perfectly with the structure of prymnesin,” said Shende.

Following the cascade of reactions that golden algae uses to make its toxin revealed previously unknown strategies for making chemicals in nature, said Moore. “The hope is that we can use this knowledge of how nature makes these complex chemicals to open up new chemical possibilities in the lab for the medicines and materials of tomorrow,” he added.

Finding the genes behind the prymnesin toxin could allow for more cost effective monitoring for golden algae blooms. Such monitoring could use tests to detect the PKZILLA genes in the environment akin to the PCR tests that became familiar during the COVID-19 pandemic. Improved monitoring could boost preparedness and allow for more detailed study of the conditions that make blooms more likely to occur.

Fallon said the PKZILLA genes the team discovered are the first genes ever causally linked to the production of any marine toxin in the polyether group that prymnesin is part of.

Next, the researchers hope to apply the non-standard screening techniques they used to find the PKZILLA genes to other species that produce polyether toxins. If they can find the genes behind other polyether toxins, such as ciguatoxin which may affect up to 500,000 people annually, it would open up the same genetic monitoring possibilities for a suite of other toxic algal blooms with significant global impacts.

In addition to Fallon, Moore and Shende from Scripps, David Gonzalez and Igor Wierzbikci of UC San Diego along with Amanda Pendleton, Nathan Watervoort, Robert Auber and Jennifer Wisecaver of Purdue University co-authored the study.

Share Button