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Bacterial sensors send a jolt of electricity when triggered

HOUSTON – (Nov. 2, 2022) – When you hit your finger with a hammer, you feel the pain immediately. And you react immediately. Credit: Brandon Martin/Rice…

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HOUSTON – (Nov. 2, 2022) – When you hit your finger with a hammer, you feel the pain immediately. And you react immediately.

Credit: Brandon Martin/Rice University

HOUSTON – (Nov. 2, 2022) – When you hit your finger with a hammer, you feel the pain immediately. And you react immediately.

But what if the pain comes 20 minutes after the hit? By then, the injury might be harder to heal. 

Scientists and engineers at Rice University say the same is true for the environment. If a chemical spill in a river goes unnoticed for 20 minutes, it might be too late to remediate.

Their living bioelectronic sensors can help. A team led by Rice synthetic biologists Caroline Ajo-Franklin and Jonathan (Joff) Silberg and lead authors Josh Atkinson and Lin Su, both Rice alumni, have engineered bacteria to quickly sense and report on the presence of a variety of contaminants. 

Their study in Nature shows the cells can be programmed to identify chemical invaders and report within minutes by releasing a detectable electrical current. 

Such “smart” devices could power themselves by scavenging energy in the environment as they monitor conditions in settings like rivers, farms, industry and wastewater treatment plants and to ensure water security, according to the researchers.

The environmental information communicated by these self-replicating bacteria can be customized by replacing a single protein in the eight-component, synthetic electron transport chain that gives rise to the sensor signal.

“I think it’s the most complex protein pathway for real-time signaling that has been built to date,” said Silberg, director of Rice’s Systems, Synthetic and Physical Biology Ph.D. Program. “To put it simply, imagine a wire that directs electrons to flow from a cellular chemical to an electrode, but we’ve broken the wire in the middle. When the target molecule hits, it reconnects and electrifies the full pathway.”

“It’s literally a miniature electrical switch,” Ajo-Franklin said. 

“You put the probes into the water and measure the current,” she said. “It’s that simple. Our devices are different because the microbes are encapsulated. We’re not releasing them into the environment.” 

The researchers’ proof-of-concept bacteria was Escherichia coli, and their first target was thiosulfate, a dichlorination agent used in water treatment that can cause algae blooms. And there were convenient sources of water to test: Galveston Beach and Houston’s Brays and Buffalo bayous.

They collected water from each. At first, they attached their E. coli to electrodes, but the microbes refused to stay put. “They don’t naturally stick to an electrode,” Ajo-Franklin said. “We’re using strains that don’t form biofilms, so when we added water, they’d fall off.”

When that happened, the electrodes delivered more noise than signal. 

Enlisting co-author Xu Zhang, a postdoctoral researcher in Ajo-Franklin’s lab, they encapsulated sensors into agarosein the shape of a lollipop that allowed contaminants in but held the sensors in place, reducing the noise. 

“Xu’s background is in environmental engineering,” Ajo-Franklin said. “She didn’t come in and say, ‘Oh, we have to fix the biology.’ She said, ‘What can we do with the materials?’ It took great, innovative work on the materials side to make the synthetic biology shine.”

With the physical constraints in place, the labs first encoded E. coli to express a synthetic pathway that only generates current when it encounters thiosulfate. This living sensor was able to sense this chemical at levels less than 0.25 millimoles per liter, far lower than levels toxic to fish.

In another experiment, E. coli was recoded to sense an endocrine disruptor. This also worked well, and the signals were greatly enhanced when conductive nanoparticles custom-synthesized by Su were encapsulated with the cells in the agarose lollipop. The researchers reported these encapsulated sensors detect this contaminant up to 10 times faster than the previous state-of-the-art devices. 

The study began by chance when Atkinson and Moshe Baruch of Ajo-Franklin’s group at Berkeley Lawrence National Laboratory set up next to each other at a 2015 synthetic biology conference in Chicago, with posters they quickly realized outlined different aspects of the same idea.

“We had neighboring posters because of our last names,” said Atkinson. “We spent most of the poster session chatting about each other’s projects and how there were clear synergies in our interests in interfacing cells with electrodes and electrons as an information carrier.” 

“Josh’s poster had our first module: how to take chemical information and turn it into biochemical information,” Ajo-Franklin recalled. “Moshe had the third module: How to take biochemical information and turn it into an electrical signal.

“The catch was how to link these together,” she said. “The biochemical signals were a little different.”

“We said, ‘We need to get together and talk about this!’” Silberg recalled. Within six months, the new collaborators won seed funding from the Office of Naval Research, followed by a grant, to develop the idea.

“Joff’s group brought in the protein engineering and half of the electron transfer pathway,” Ajo-Franklin said. “My group brought the other half of the electron transport pathway and some of the materials efforts.” The collaboration ultimately brought Ajo-Franklin herself to Rice in 2019 as a CPRIT Scholar.

“We have to give so much credit to Lin and Josh,” she said. “They never gave up on this project, and it was incredibly synergistic. They would bounce ideas back and forth and through that interchange solved a lot of problems.” 

“Each of which another student could spend years on,” Silberg added.

“Both Josh and I spent several years of our Ph.D.s working on this, with the pressure of graduating and moving on to the next stage of our careers,” said Su, a visiting graduate student in Ajo-Franklin’s lab after graduating from Southeast University in China. “I had to extend my visa multiple times to stay and finish the research.”

Silberg said the design’s complexity goes far beyond the signaling pathway. “The chain has eight components that control electron flow, but there are other components that build the wires that go into the molecules,” he said. “There are a dozen-and-a-half components with almost 30 metal or organic cofactors. This thing’s massive compared to something like our mitochondrial respiratory chains.” 

All credited the invaluable assistance of co-author George Bennett, Rice’s E. Dell Butcher Professor Emeritus and a research professor in biosciences, in making the necessary connections.

Silberg said he sees engineered microbes performing many tasks in the future, from monitoring the gut microbiome to sensing contaminants like viruses, improving upon the successful strategy of testing wastewater plants for SARS-CoV-19 during the pandemic.

“Real-time monitoring becomes pretty important with those transient pulses,” he said. “And because we grow these sensors, they’re potentially pretty cheap to make.” 

To that end, the team is collaborating with Rafael Verduzco, a Rice professor of chemical and biomolecular engineering and of materials science and nanoengineering who leads a recent $2 million National Science Foundation grant with Ajo-Franklin, Silberg, bioscientist Kirstin Matthews and civil and environmental engineer Lauren Stadler to develop real-time wastewater monitoring.

“The type of materials we can make with Raphael takes this to a whole new level,” Ajo-Franklin said. 

Silberg said the Rice labs are working on design rules to develop a library of modular sensors. “I hope that when people read this, they recognize the opportunities,” he said.

Silberg is the Stewart Memorial Professor of BioSciences and a professor of bioengineering at Rice. Ajo-Franklin is a professor of biosciences. Atkinson is a visiting National Science Foundation postdoctoral fellow at Aarhus University, Denmark, and has an affiliation with the University of Southern California. Su is a postdoctoral research associate and a Leverhulme Early Career Fellow at the University of Cambridge.

The research was supported by the Office of Science, Office of Basic Energy Sciences of the U.S. Department of Energy (DE-SC0014462), the Office of Naval Research (0001418IP00037, N00014-17-1-2639, N00014-20-1-2274), the Cancer Prevention and Research Institute of Texas (RR190063), the National Science Foundation (1843556), the Department of Energy Office of Science Graduate Student Research Program (DE SC0014664), the Lodieska Stockbridge Vaughn Fellowship and the China Scholarship Council Fellowship (CSC-201606090098).

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Read the abstract at https://www.nature.com/articles/s41586-022-05356-y.

This news release can be found online at https://news.rice.edu/news/2022/bacterial-sensors-send-jolt-electricity-when-triggered.

Follow Rice News and Media Relations via Twitter @RiceUNews.

Related materials:

Rice lab grows macroscale, modular materials from bacteria: https://news.rice.edu/news/2022/rice-lab-grows-macroscale-modular-materials-bacteria

Switch-in-a-cell electrifies life: https://news2.rice.edu/2018/12/17/switch-in-a-cell-electrifies-life-2/

Bacterial ‘bully’ could improve food production: https://news.rice.edu/news/2022/bacterial-bully-could-improve-food-production

Living sensor research wins federal backing: https://news.rice.edu/news/2022/living-sensor-research-wins-federal-backing

Labs give ancient proteins new purpose: https://news2.rice.edu/2019/07/01/labs-give-ancient-proteins-new-purpose-2/

‘Bloggers’ and ‘spies’ will clarify marine processes: https://news2.rice.edu/2018/05/18/bloggers-and-spies-will-clarify-marine-processes-2/

Systems, Synthetic and Physical Biology Ph.D. Program: https://sspb.rice.edu

Silberg Lab: https://www.silberglab.org

Ajo-Franklin Lab: https://cafgroup.rice.edu

Polymer Engineering Laboratory (Verduzco): http://verduzcolab.blogs.rice.edu

Bennett Lab: http://www.bioc.rice.edu/~gbennett/

Video: 

Produced by Brandon Martin/Rice University

Images for download:

https://news-network.rice.edu/news/files/2022/10/1107_SENSORS-1-web.jpg

Pucklike bioelectronics designed at Rice University contain programmable bacteria and are attached to an electrode that delivers a signal when they detect a target contaminant, enabling real-time sensing. (Credit: Brandon Martin/Rice University)

https://news-network.rice.edu/news/files/2022/10/1107_SENSORS-2-web.jpg

Pucklike devices designed by Rice University scientists and engineers contain multitudes of programmable bacteria that can detect contaminants and report their presence in real time. The bacteria release an electrical signal when triggered. (Credit: Brandon Martin/Rice University)

https://news-network.rice.edu/news/files/2022/10/1107_SENSORS-3-web.jpg

Xu Zhang, a postdoctoral researcher at Rice University, pulls a water sample from Houston’s Buffalo Bayou for testing with engineered living microbes designed to detect contaminants. When the microbes find evidence of a target contaminant, they release an electrical signal that can be read almost immediately. (Credit: Brandon Martin/Rice University) 

https://news-network.rice.edu/news/files/2022/10/1107_SENSORS-4-web.jpg

Rice University synthetic biologists Caroline Ajo-Franklin and Joff Silberg and their labs have developed programmable bacteria that sense contaminants and release an electronic signal in real time. (Credit: Brandon Martin/Rice University)

https://news-network.rice.edu/news/files/2022/10/1107_SENSORS-5-web.jpg

Rice University postdoctoral researcher Xu Zhang prepares a water sample for testing with programmable bacteria that test for contaminants and release an electronic signal for detection in real time. (Credit: Brandon Martin/Rice University)

Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation’s top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 4,240 undergraduates and 3,972 graduate students, Rice’s undergraduate student-to-faculty ratio is just under 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is ranked No. 1 for lots of race/class interaction and No. 1 for quality of life by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger’s Personal Finance.


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The next pandemic? It’s already here for Earth’s wildlife

Bird flu is decimating species already threatened by climate change and habitat loss.

I am a conservation biologist who studies emerging infectious diseases. When people ask me what I think the next pandemic will be I often say that we are in the midst of one – it’s just afflicting a great many species more than ours.

I am referring to the highly pathogenic strain of avian influenza H5N1 (HPAI H5N1), otherwise known as bird flu, which has killed millions of birds and unknown numbers of mammals, particularly during the past three years.

This is the strain that emerged in domestic geese in China in 1997 and quickly jumped to humans in south-east Asia with a mortality rate of around 40-50%. My research group encountered the virus when it killed a mammal, an endangered Owston’s palm civet, in a captive breeding programme in Cuc Phuong National Park Vietnam in 2005.

How these animals caught bird flu was never confirmed. Their diet is mainly earthworms, so they had not been infected by eating diseased poultry like many captive tigers in the region.

This discovery prompted us to collate all confirmed reports of fatal infection with bird flu to assess just how broad a threat to wildlife this virus might pose.

This is how a newly discovered virus in Chinese poultry came to threaten so much of the world’s biodiversity.

H5N1 originated on a Chinese poultry farm in 1997. ChameleonsEye/Shutterstock

The first signs

Until December 2005, most confirmed infections had been found in a few zoos and rescue centres in Thailand and Cambodia. Our analysis in 2006 showed that nearly half (48%) of all the different groups of birds (known to taxonomists as “orders”) contained a species in which a fatal infection of bird flu had been reported. These 13 orders comprised 84% of all bird species.

We reasoned 20 years ago that the strains of H5N1 circulating were probably highly pathogenic to all bird orders. We also showed that the list of confirmed infected species included those that were globally threatened and that important habitats, such as Vietnam’s Mekong delta, lay close to reported poultry outbreaks.

Mammals known to be susceptible to bird flu during the early 2000s included primates, rodents, pigs and rabbits. Large carnivores such as Bengal tigers and clouded leopards were reported to have been killed, as well as domestic cats.

Our 2006 paper showed the ease with which this virus crossed species barriers and suggested it might one day produce a pandemic-scale threat to global biodiversity.

Unfortunately, our warnings were correct.

A roving sickness

Two decades on, bird flu is killing species from the high Arctic to mainland Antarctica.

In the past couple of years, bird flu has spread rapidly across Europe and infiltrated North and South America, killing millions of poultry and a variety of bird and mammal species. A recent paper found that 26 countries have reported at least 48 mammal species that have died from the virus since 2020, when the latest increase in reported infections started.

Not even the ocean is safe. Since 2020, 13 species of aquatic mammal have succumbed, including American sea lions, porpoises and dolphins, often dying in their thousands in South America. A wide range of scavenging and predatory mammals that live on land are now also confirmed to be susceptible, including mountain lions, lynx, brown, black and polar bears.

The UK alone has lost over 75% of its great skuas and seen a 25% decline in northern gannets. Recent declines in sandwich terns (35%) and common terns (42%) were also largely driven by the virus.

Scientists haven’t managed to completely sequence the virus in all affected species. Research and continuous surveillance could tell us how adaptable it ultimately becomes, and whether it can jump to even more species. We know it can already infect humans – one or more genetic mutations may make it more infectious.

At the crossroads

Between January 1 2003 and December 21 2023, 882 cases of human infection with the H5N1 virus were reported from 23 countries, of which 461 (52%) were fatal.

Of these fatal cases, more than half were in Vietnam, China, Cambodia and Laos. Poultry-to-human infections were first recorded in Cambodia in December 2003. Intermittent cases were reported until 2014, followed by a gap until 2023, yielding 41 deaths from 64 cases. The subtype of H5N1 virus responsible has been detected in poultry in Cambodia since 2014. In the early 2000s, the H5N1 virus circulating had a high human mortality rate, so it is worrying that we are now starting to see people dying after contact with poultry again.

It’s not just H5 subtypes of bird flu that concern humans. The H10N1 virus was originally isolated from wild birds in South Korea, but has also been reported in samples from China and Mongolia.

Recent research found that these particular virus subtypes may be able to jump to humans after they were found to be pathogenic in laboratory mice and ferrets. The first person who was confirmed to be infected with H10N5 died in China on January 27 2024, but this patient was also suffering from seasonal flu (H3N2). They had been exposed to live poultry which also tested positive for H10N5.

Species already threatened with extinction are among those which have died due to bird flu in the past three years. The first deaths from the virus in mainland Antarctica have just been confirmed in skuas, highlighting a looming threat to penguin colonies whose eggs and chicks skuas prey on. Humboldt penguins have already been killed by the virus in Chile.

A colony of king penguins.
Remote penguin colonies are already threatened by climate change. AndreAnita/Shutterstock

How can we stem this tsunami of H5N1 and other avian influenzas? Completely overhaul poultry production on a global scale. Make farms self-sufficient in rearing eggs and chicks instead of exporting them internationally. The trend towards megafarms containing over a million birds must be stopped in its tracks.

To prevent the worst outcomes for this virus, we must revisit its primary source: the incubator of intensive poultry farms.

Diana Bell does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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A major cruise line is testing a monthly subscription service

The Cruise Scarlet Summer Season Pass was designed with remote workers in mind.

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While going on a cruise once meant disconnecting from the world when between ports because any WiFi available aboard was glitchy and expensive, advances in technology over the last decade have enabled millions to not only stay in touch with home but even work remotely.

With such remote workers and digital nomads in mind, Virgin Voyages has designed a monthly pass that gives those who want to work from the seas a WFH setup on its Scarlet Lady ship — while the latter acronym usually means "work from home," the cruise line is advertising as "work from the helm.”

Related: Royal Caribbean shares a warning with passengers

"Inspired by Richard Branson's belief and track record that brilliant work is best paired with a hearty dose of fun, we're welcoming Sailors on board Scarlet Lady for a full month to help them achieve that perfect work-life balance," Virgin Voyages said in announcing its new promotion. "Take a vacation away from your monotonous work-from-home set up (sorry, but…not sorry) and start taking calls from your private balcony overlooking the Mediterranean sea."

A man looks through his phone while sitting in a hot tub on a cruise ship.

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This is how much it'll cost you to work from a cruise ship for a month

While the single most important feature for successful work at sea — WiFi — is already available for free on Virgin cruises, the new Scarlet Summer Season Pass includes a faster connection, a $10 daily coffee credit, access to a private rooftop, and other member-only areas as well as wash and fold laundry service that Virgin advertises as a perk that will allow one to concentrate on work

More Travel:

The pass starts at $9,990 for a two-guest cabin and is available for four monthlong cruises departing in June, July, August, and September — each departs from ports such as Barcelona, Marseille, and Palma de Mallorca and spends four weeks touring around the Mediterranean.

Longer cruises are becoming more common, here's why

The new pass is essentially a version of an upgraded cruise package with additional perks but is specifically tailored to those who plan on working from the ship as an opportunity to market to them.

"Stay connected to your work with the fastest at-sea internet in the biz when you want and log-off to let the exquisite landscape of the Mediterranean inspire you when you need," reads the promotional material for the pass.

Amid the rise of remote work post-pandemic, cruise lines have been seeing growing interest in longer journeys in which many of the passengers not just vacation in the traditional sense but work from a mobile office.

In 2023, Turkish cruise line operator Miray even started selling cabins on a three-year tour around the world but the endeavor hit the rocks after one of the engineers declared the MV Gemini ship the company planned to use for the journey "unseaworthy" and the cruise ship line dealt with a PR scandal that ultimately sank the project before it could take off.

While three years at sea would have set a record as the longest cruise journey on the market, companies such as Royal Caribbean  (RCL) (both with its namesake brand and its Celebrity Cruises line) have been offering increasingly long cruises that serve as many people’s temporary homes and cross through multiple continents.

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As the pandemic turns four, here’s what we need to do for a healthier future

On the fourth anniversary of the pandemic, a public health researcher offers four principles for a healthier future.

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John Gomez/Shutterstock

Anniversaries are usually festive occasions, marked by celebration and joy. But there’ll be no popping of corks for this one.

March 11 2024 marks four years since the World Health Organization (WHO) declared COVID-19 a pandemic.

Although no longer officially a public health emergency of international concern, the pandemic is still with us, and the virus is still causing serious harm.

Here are three priorities – three Cs – for a healthier future.

Clear guidance

Over the past four years, one of the biggest challenges people faced when trying to follow COVID rules was understanding them.

From a behavioural science perspective, one of the major themes of the last four years has been whether guidance was clear enough or whether people were receiving too many different and confusing messages – something colleagues and I called “alert fatigue”.

With colleagues, I conducted an evidence review of communication during COVID and found that the lack of clarity, as well as a lack of trust in those setting rules, were key barriers to adherence to measures like social distancing.

In future, whether it’s another COVID wave, or another virus or public health emergency, clear communication by trustworthy messengers is going to be key.

Combat complacency

As Maria van Kerkove, COVID technical lead for WHO, puts it there is no acceptable level of death from COVID. COVID complacency is setting in as we have moved out of the emergency phase of the pandemic. But is still much work to be done.

First, we still need to understand this virus better. Four years is not a long time to understand the longer-term effects of COVID. For example, evidence on how the virus affects the brain and cognitive functioning is in its infancy.

The extent, severity and possible treatment of long COVID is another priority that must not be forgotten – not least because it is still causing a lot of long-term sickness and absence.

Culture change

During the pandemic’s first few years, there was a question over how many of our new habits, from elbow bumping (remember that?) to remote working, were here to stay.

Turns out old habits die hard – and in most cases that’s not a bad thing – after all handshaking and hugging can be good for our health.

But there is some pandemic behaviour we could have kept, under certain conditions. I’m pretty sure most people don’t wear masks when they have respiratory symptoms, even though some health authorities, such as the NHS, recommend it.

Masks could still be thought of like umbrellas: we keep one handy for when we need it, for example, when visiting vulnerable people, especially during times when there’s a spike in COVID.

If masks hadn’t been so politicised as a symbol of conformity and oppression so early in the pandemic, then we might arguably have seen people in more countries adopting the behaviour in parts of east Asia, where people continue to wear masks or face coverings when they are sick to avoid spreading it to others.

Although the pandemic led to the growth of remote or hybrid working, presenteeism – going to work when sick – is still a major issue.

Encouraging parents to send children to school when they are unwell is unlikely to help public health, or attendance for that matter. For instance, although one child might recover quickly from a given virus, other children who might catch it from them might be ill for days.

Similarly, a culture of presenteeism that pressures workers to come in when ill is likely to backfire later on, helping infectious disease spread in workplaces.

At the most fundamental level, we need to do more to create a culture of equality. Some groups, especially the most economically deprived, fared much worse than others during the pandemic. Health inequalities have widened as a result. With ongoing pandemic impacts, for example, long COVID rates, also disproportionately affecting those from disadvantaged groups, health inequalities are likely to persist without significant action to address them.

Vaccine inequity is still a problem globally. At a national level, in some wealthier countries like the UK, those from more deprived backgrounds are going to be less able to afford private vaccines.

We may be out of the emergency phase of COVID, but the pandemic is not yet over. As we reflect on the past four years, working to provide clearer public health communication, avoiding COVID complacency and reducing health inequalities are all things that can help prepare for any future waves or, indeed, pandemics.

Simon Nicholas Williams has received funding from Senedd Cymru, Public Health Wales and the Wales Covid Evidence Centre for research on COVID-19, and has consulted for the World Health Organization. However, this article reflects the views of the author only, in his academic capacity at Swansea University, and no funding or organizational bodies were involved in the writing or content of this article.

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