In a new study in Nature Communications, an international team including scientists from the Marine Biological Laboratory (MBL) and the University of Chicago identified a new mobile DNA element in Wolbachia, which may contribute to improved control strategies for mosquito vectors of disease.

Led by Julie Reveillaud of INRA, France, and Sarah Bordenstein of Vanderbilt University, the researchers reconstructed near-complete genomes of Wolbachia isolated from individual ovaries of four Culex pipiens mosquitoes. In the process, they identified a novel plasmid — a circular piece of DNA that can replicate independently of the chromosomes. A plasmid is a mobile DNA element, meaning it can transfer from one cell to another and can have great implications for the fitness and evolution of a microbial species. Due to the ability of mobile genetic elements to spread through different Wolbachia cells, and thus across a Wolbachia population, they hold promise for controlling mosquito populations that may carry disease.

“Our data show that this novel plasmid is widespread across natural Wolbachia populations that infect C. pipiens mosquitoes throughout the world, which implies it has an essential role. The idea that it may enable transformation of the Wolbachia populations is simply very exciting,” says the senior author of the study, A. Murat Eren (Meren), an assistant professor of medicine at the University of Chicago and an MBL Fellow.

Wolbachia is transmitted from mother to offspring and can influence the reproductive behavior of its mosquito host. Wolbachia can modify sperm so if an infected male mates with an uninfected female, or with one that carries a different strain of Wolbachia, embryos cannot develop. The mechanism behind this embryonic killing lies within another mobile genetic element in the Wolbachia genome.

“Wolbachia populations do not lend themselves to direct genetic modification. While a natural plasmid sounds very promising to bypass those limitations, we do not yet have any evidence to suggest the possibility or efficacy of any transformation through this plasmid,” Meren says. “We just discovered its existence, and the time will tell how useful it is.”

“Other exciting questions for which we do not have yet clear answers include whether there is an ancestral relationship between the plasmid and other mobile genetic elements of Wolbachia, and whether these interact or not,” adds Reveillaud.

This collaboration began at MBL in 2011, when Meren and Reveillaud brought their computational and molecular evolution backgrounds together to explore questions in microbial ecology in the MBL’s Bay Paul Center.  Years later, they began examining Wolbachia genomic diversity by focusing on individual mosquitoes captured in the wild, rather than using laboratory mosquito strains. With the help of former MBL scientists Sarah Bordenstein and Seth Bordenstein of Vanderbilt University, who have expertise in Wolbachia, they began unraveling the intricacies of the Wolbachia genome.

“Wolbachia is particularly difficult to study because, unlike free-living bacteria, it cannot be cultured in cell-free media. Through this interdisciplinary collaboration, we were able to tease apart the genomes of the mosquito host, Wolbachia, and its mobile elements,” says Sarah Bordenstein.

While fragments of this novel plasmid had appeared in previous Wolbachia sequencing studies, these fragments had never been assembled into a complete circular piece and its extrachromosomal nature was not recognized, most likely due to computational limitations. The team was able to overcome these limitations by employing a combination of cutting-edge strategies, such as genome-resolved metagenomics and long-read sequencing.

“The key bioinformatics platform that enabled us to study mosquito metagenomes and Wolbachia pangenomes in this study, and the connections between scientists with distinct skills that made this discovery possible, were developed at the MBL,” Meren says. “Almost everyone in this paper is somehow linked to the MBL.”

A toilet-seat based cardiovascular monitoring system created by a team of Rochester Institute of Technology researchers aims to lower the hospital readmission rates of patients with congestive heart failure. The toilet seats, which will be brought through the FDA clearance process by the researchers’ company Heart Health Intelligence, would be purchased by hospitals and issued to heart failure patients after discharge. The toilet seats are equipped to measure the electrical and mechanical activity of the heart, and can monitor heart rate, blood pressure, blood oxygenation levels, and the patient’s weight and stroke volume, which is the amount of blood pumped out of the heart at every beat. Algorithms analyze the data, and with further development, will alert advanced practice providers of a deteriorating condition. A report will be passed along to cardiologists who will then determine if intervention is necessary.

Nicholas Conn, a postdoctoral fellow at RIT and founder and CEO of Heart Health Intelligence, is part of the university team that developed the toilet seats.

“Typically, within 30 days of hospital discharge, 25 percent of patients with congestive heart failure are readmitted,” said Conn. “After 90 days of hospital discharge, 45 percent of patients are readmitted. And the Centers for Medicare and Medicaid Services is penalizing hospitals for readmitting patients for heart failure.”

Conn, the company’s chief executive officer, further explains that using the national average for readmission rates, the penalty alone for readmitting 150 patients is approximately $500,000 annually. The total cost of providing 150 patients with their own monitored toilet seats from HHI is $200,000. With that investment, he says, hospital systems will save more than double their initial investment within one year.

According to Conn, who earned three degrees from RIT — a bachelor’s degree and a master’s degree in electrical engineering in 2011 and 2013, respectively, and a doctoral degree in microsystems engineering in 2016 — the system will pick up deteriorating conditions before the patients even realize they are symptomatic. And with the rapid data analysis, interventions can be as simple as a drug change or short office visit, instead of an admission to the hospital.

HHI, which joined RIT’s Venture Creations business incubator earlier this year, is now focused on moving the product forward. The team is heavily involved in writing grants for additional funding and networking, and human-subject testing and pre-clinical studies are well underway. Conn and his team are working on approving the product with the FDA and rolling it out across the country.

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Current robots are usually self-contained entities made of interdependent subcomponents, each with a specific function. If one part fails, the robot stops working. In robotic swarms, each robot is an independently functioning machine.

In a new study published today in Nature, researchers at Columbia Engineering and MIT Computer Science & Artificial Intelligence Lab (CSAIL), demonstrate for the first time a way to make a robot composed of many loosely coupled components, or “particles.” Unlike swarm or modular robots, each component is simple, and has no individual address or identity. In their system, which the researchers call a “particle robot,” each particle can perform only uniform volumetric oscillations (slightly expanding and contracting), but cannot move independently.

The team, led by Hod Lipson, professor of mechanical engineering at Columbia Engineering, and CSAIL Director Daniela Rus, discovered that when they grouped thousands of these particles together in a “sticky” cluster and made them oscillate in reaction to a light source, the entire particle robot slowly began to move forward, towards the light.

“You can think of our new robot as the proverbial “Gray Goo,” says Lipson. “Our robot has no single point of failure and no centralized control. It’s still fairly primitive, but now we know that this fundamental robot paradigm is actually possible. We think it may even explain how groups of cells can move together, even though individual cells cannot.”

Researchers have been building autonomous robots for more than a century, but these have been non-biological machines that cannot grow, heal, or recover from damage. The Columbia Engineering/MIT team has been focused on developing robust, scalable robots that can function even when individual components fail.

“We’ve been trying to fundamentally rethink our approach to robotics, to discover if there is a way to make robots differently,” says Lipson who directs the Creative Machines lab. “Not just make a robot look like a biological creature but actually construct it like a biological system, to create something that is vast in complexity and abilities yet composed of fundamentally simple parts.”

Rus, who is also the Andrew (1956) and Erna Viterbi Professor of Electrical Engineering and Computer Science at MIT, adds, “All creatures in nature are made of cells that combine in different ways to make organisms. In developing particle robots, the question we ask is, can we have robotic cells that can be composed in different ways to make different robots? The robot could have the best shape required by the task — a snake to crawl through a tunnel or a three-handed machine for a factory floor. We could even give these particle robots the ability to make themselves. Suppose, for example, that a robot needs a screw driver from the table — the screw driver is too far to reach. What if the robot could reshuffle its cells to grow an extra long arm? As its goals change, its body can change too.”

The team, working with Chuck Hoberman at Harvard’s Wyss Institute and other researchers at Cornell, used many identical components, or particles, that could perform a simple motion like expansion and contraction. In simulations, they demonstrated robots comprising 100,000 particles. Experimentally, they demonstrated a system comprising two dozen particles.

“The particles closer to the light source experience brighter light and thus start their cycle earlier,” explains Shuguang Li, co-first author of the paper who conducted the physical experiments. Li, who was a postdoctoral fellow in Lipson’s former lab at Cornell and is currently a postdoc with Rus at CSAIL, continues. “That movement creates a sort of wave throughout the cluster, from the ones closer to the light to the ones further away, and that wave makes the entire cluster move towards the light. The movement toward light creates a global motion, even though the individual particles cannot move independently.”

Modeling this behavior in simulations, they explored obstacle avoidance and object transport at greater scales, with hundreds and thousands of particles. They were also able to demonstrate the resilience of their particle robot paradigm both to noisy components and to individual failure.

“We found that our particle robots maintained approximately half of their fully functioning speed even when 20 percent of the particles are dead,” says Richa Batra, co-first author of the paper and Lipson’s PhD student who led the simulation studies.

The team is already testing their system with a larger number of cm-scale particles. They are also exploring other forms of particle robots, such as vibrating microspeheres.

“We think it will be possible one day to make these kinds of robots from millions of tiny particles, like microbeads that respond to sound or light or chemical gradient,” says Lipson. “Such robots could be used to do things like clean up areas or explore unknown terrains/structures.”

Video: https://www.youtube.com/watch?v=wrDdqjQvaoA