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Wednesday, October 23rd, 2019
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Event |
| 10:55a |
MIT announces framework to guide negotiations with publishers The MIT Libraries, together with the MIT Committee on the Library System and the Ad Hoc Task Force on Open Access to MIT’s Research, announced that it has developed a principle-based framework to guide negotiations with scholarly publishers. The framework emerges directly from the core principles for open science and open scholarship articulated in the recommendations of the Task Force on Open Access to MIT’s Research, which released its final report to the MIT community on Oct. 17.
The framework affirms the overarching principle that control of scholarship and its dissemination should reside with scholars and their institutions. It aims to ensure that scholarly research outputs are openly and equitably available to the broadest possible audience, while also providing valued services to the MIT community.
“The value of scholarly content primarily comes from researchers, authors, and peer reviewers — the people who are creating knowledge and reviewing and improving it,” says Roger Levy, associate professor of brain and cognitive sciences and chair of the Committee on the Library System. “We think authors should have considerable rights to their own intellectual outputs.”
In MIT’s model, institutions and scholars maintain the rights to share their work openly via institutional repositories, and publishers are paid for the services valued by authors and readers, such as curation and peer-review management.
“The MIT Framework gives us a starting point for imagining journals as a service,” says Chris Bourg, director of the MIT Libraries.
The framework was developed by members of the Open Access Task Force, the Committee on the Library System, and MIT Libraries staff, and vetted by faculty groups across the Institute.
“The ideas in the framework are not new for MIT, which has been a leader in sharing its knowledge with the world,” says Bourg. “This is a clear articulation by the MIT faculty of what they want in scholarly communications — a scholar-led, open, and equitable environment that promises to advance knowledge and its applications. It is also a model that we think will be appealing for a diverse range of scholarly institutions, from private research-intensive universities like MIT to small liberal arts colleges and large public universities.”
“The six core principles of the MIT Framework free researchers and research institutions to follow their own lights in sharing their research, and help ensure that scholarly communities will retain control of scholarly communication,” says Peter Suber, director of the Harvard University Library Office for Scholarly Communication.
While MIT intends to rely on this framework as a guide for relationships with publishers regardless of the actions of any peer institutions or other organizations, institutions ranging from large research universities to liberal arts colleges have decided to endorse the framework in recognition of its potential to advance open scholarship and the public good.
“The MIT Framework values the labor and rights of authors, while respecting a role for journals and publishers,” says Janelle Wertzberger, assistant dean and director of scholarly communications at Gettysburg College. “It balances author rights with user benefits by ensuring that published research will reach the widest possible audience. This approach aims to realign the current publishing system with the needs of all stakeholders within the system, and thereby creates positive change for all.”
A full list of endorsers is available at libraries.mit.edu/scholarly/publishing/framework. Additional institutions are also invited to add their endorsement on this page.
MIT originally passed its Faculty Open Access Policy in 2009; it was one of the first in the country and the first to be adopted university-wide. Today close to 50 percent of MIT faculty-authored journal articles are freely available in DSpace@MIT, the Institute’s repository. | | 1:00p |
Biologists build proteins that avoid crosstalk with existing molecules Inside a living cell, many important messages are communicated via interactions between proteins. For these signals to be accurately relayed, each protein must interact only with its specific partner, avoiding unwanted crosstalk with any similar proteins.
A new MIT study sheds light on how cells are able to prevent crosstalk between these proteins, and also shows that there remains a huge number of possible protein interactions that cells have not used for signaling. This means that synthetic biologists could generate new pairs of proteins that can act as artificial circuits for applications such as diagnosing disease, without interfering with cells’ existing signaling pathways.
“Using our high-throughput approach, you can generate many orthogonal versions of a particular interaction, allowing you to see how many different insulated versions of that protein complex can be built,” says Conor McClune, an MIT graduate student and the lead author of the study.
In the new paper, which appears today in Nature, the researchers produced novel pairs of signaling proteins and demonstrated how they can be used to link new signals to new outputs by engineering E. coli cells that produce yellow fluorescence after encountering a specific plant hormone.
Michael Laub, an MIT professor of biology, is the senior author of the study. Other authors are recent MIT graduate Aurora Alvarez-Buylla and Christopher Voigt, the Daniel I.C. Wang Professor of Advanced Biotechnology.
New combinations
In this study, the researchers focused on a type of signaling pathway called two-component signaling, which is found in bacteria and some other organisms. A wide variety of two-component pathways has evolved through a process in which cells duplicate genes for signaling proteins they already have, and then mutate them, creating families of similar proteins.
“It’s intrinsically advantageous for organisms to be able to expand this small number of signaling families quite dramatically, but it runs the risk that you’re going to have crosstalk between these systems that are all very similar,” Laub says. “It then becomes an interesting challenge for cells: How do you maintain the fidelity of information flow, and how do you couple specific inputs to specific outputs?”
Most of these signaling pairs consist of an enzyme called a kinase and its substrate, which is activated by the kinase. Bacteria can have dozens or even hundreds of these protein pairs relaying different signals.
About 10 years ago, Laub showed that the specificity between bacterial kinases and their substrates is determined by only five amino acids in each of the partner proteins. This raised the question of whether cells have already used up, or are coming close to using up, all of the possible unique combinations that won’t interfere with existing pathways.
Some previous studies from other labs had suggested that the possible number of interactions that would not interfere with each other might be running out, but the evidence was not definitive. The MIT researchers decided to take a systematic approach in which they began with one pair of existing E. coli signaling proteins, known as PhoQ and PhoP, and then introduced mutations in the regions that determine their specificity.
This yielded more than 10,000 pairs of proteins. The researchers tested each kinase to see if they would activate any of the substrates, and identified about 200 pairs that interact with each other but not the parent proteins, the other novel pairs, or any other type of kinase-substrate family found in E. coli.
“What we found is that it’s pretty easy to find combinations that will work, where two proteins interact to transduce a signal and they don’t talk to anything else inside the cell,” Laub says.
He now plans to try to reconstruct the evolutionary history that has led to certain protein pairs being used by cells while many other possible combinations have not naturally evolved.
Synthetic circuits
This study also offers a new strategy for creating new synthetic biology circuits based on protein pairs that don’t crosstalk with other cellular proteins, the researchers say. To demonstrate that possibility, they took one of their new protein pairs and modified the kinase so that it would be activated by a plant hormone called trans-zeatin, and engineered the substrate so that it would glow yellow when the kinase activated it.
“This shows that we can overcome one of the challenges of putting a synthetic circuit in a cell, which is that the cell is already filled with signaling proteins,” Voigt says. “When we try to move a sensor or circuit between species, one of the biggest problems is that it interferes with the pathways already there.”
One possible application for this new approach is designing circuits that detect the presence of other microbes. Such circuits could be useful for creating probiotic bacteria that could help diagnose infectious diseases.
“Bacteria can be engineered to sense and respond to their environment, with widespread applications such as ‘smart’ gut bacteria that could diagnose and treat inflammation, diabetes, or cancer, or soil microbes that maintain proper nitrogen levels and eliminate the need for fertilizer. To build such bacteria, synthetic biologists require genetically encoded ‘sensors,’” says Jeffrey Tabor, an associate professor of bioengineering and biosciences at Rice University.
“One of the major limitations of synthetic biology has been our genetic parts failing in new organisms for reasons that we don't understand (like cross-talk). What this paper shows is that there is a lot of space available to re-engineer circuits so that this doesn't happen,” says Tabor, who was not involved in the research.
If adapted for use in human cells, this approach could also help researchers design new ways to program human T cells to destroy cancer cells. This type of therapy, known as CAR-T cell therapy, has been approved to treat some blood cancers and is being developed for other cancers as well.
Although the signaling proteins involved would be different from those in this study, “the same principle applies in that the therapeutic relies on our ability to take sets of engineered proteins and put them into a novel genomic context, and hope that they don’t interfere with pathways already in the cells,” McClune says.
The research was funded by the Howard Hughes Medical Institute, the Office of Naval Research, and the National Institutes of Health Pre-Doctoral Training Grant. | | 4:00p |
New process could make hydrogen peroxide available in remote places Hydrogen peroxide, a useful all-purpose disinfectant, is found in most medicine cabinets in the developed world. But in remote villages in developing countries, where it could play an important role in health and sanitation, it can be hard to come by.
Now, a process developed at MIT could lead to a simple, inexpensive, portable device that could produce hydrogen peroxide continuously from just air, water, and electricity, providing a way to sterilize wounds, food-preparation surfaces, and even water supplies.
The new method is described this week in the journal Joule in a paper by MIT students Alexander Murray, Sahag Voskian, and Marcel Schreier and MIT professors T. Alan Hatton and Yogesh Surendranath.
Even at low concentrations, hydrogen peroxide is an effective antibacterial agent, and after carrying out its sterilizing function it breaks down into plain water, in contrast to other agents such as chlorine that can leave unwanted byproducts from its production and use.
Hydrogen peroxide is just water with an extra oxygen atom tacked on — it’s H2O2, instead of H2O. That extra oxygen is relatively loosely bound, making it a highly reactive chemical eager to oxidize any other molecules around it. It’s so reactive that in high concentrations it can be used as rocket fuel, and even concentrations of 35 percent require very special handling and shipping procedures. The kind used as a household disinfectant is typically only 3 percent hydrogen peroxide and 97 percent water.
Because high concentrations are hard to transport, and low concentrations, being mostly water, are uneconomical to ship, the material is often hard to get in places where it could be especially useful, such as remote communities with untreated water. (Bacteria in water supplies can be effectively controlled by adding hydrogen peroxide.) As a result, many research groups around the world have been pursuing approaches to developing some form of portable hydrogen peroxide production equipment.
Most of the hydrogen peroxide produced in the industrialized world is made in large chemical plants, where methane, or natural gas, is used to provide a source of hydrogen, which is then reacted with oxygen in a catalytic process under high heat. This process is energy-intensive and not easily scalable, requiring large equipment and a steady supply of methane, so it does not lend itself to smaller units or remote locations.
“There’s a growing community interested in portable hydrogen peroxide,” Surendranath says, “because of the appreciation that it would really meet a lot of needs, both on the industrial side as well as in terms of human health and sanitation.”
Other processes developed so far for potentially portable systems have key limitations. For example, most catalysts that promote the formation of hydrogen peroxide from hydrogen and oxygen also make a lot of water, leading to low concentrations of the desired product. Also, processes that involve electrolysis, as this new process does, often have a hard time separating the produced hydrogen peroxide from the electrolyte material used in the process, again leading to low efficiency.
Surendranath and the rest of the team solved the problem by breaking the process down into two separate steps. First, electricity (ideally from solar cells or windmills) is used to break down water into hydrogen and oxygen, and the hydrogen then reacts with a “carrier” molecule. This molecule — a compound called anthroquinone, in these initial experiments — is then introduced into a separate reaction chamber where it meets with oxygen taken from the outside air, and a pair of hydrogen atoms binds to an oxygen molecule (O2) to form the hydrogen peroxide. In the process, the carrier molecule is restored to its original state and returns to carry out the cycle all over again, so none of this material is consumed.
The process could address numerous challenges, Surendranath says, by making clean water, first-aid care for wounds, and sterile food preparation surfaces more available in places where they are presently scarce or unavailable.
“Even at fairly low concentrations, you can use it to disinfect water of microbial contaminants and other pathogens,” Surendranath says. And, he adds, “at higher concentrations, it can be used even to do what’s called advanced oxidation,” where in combination with UV light it can be used to decontaminate water of even strong industrial wastes, for example from mining operations or hydraulic fracking.
So, for example, a portable hydrogen peroxide plant might be set up adjacent to a fracking or mining site and used to clean up its effluent, then moved to another location once operations cease at the original site.
In this initial proof-of-concept unit, the concentration of hydrogen peroxide produced is still low, but further engineering of the system should lead to being able to produce more concentrated output, Surendranath says. “One of the ways to do that is to just increase the concentration of the mediator, and fortunately, our mediator has already been used in flow batteries at really high concentrations, so we think there’s a route toward being able to increase those concentrations,” he says.
“It’s kind of an amazing process,” he says, “because you take abundant things, water, air and electricity, that you can source locally, and you use it to make this important chemical that you can use to actually clean up the environment and for sanitation and water quality.”
“The ability to create a hydrogen peroxide solution in water without electrolytes, salt, base, etc., all of which are intrinsic to other electrochemical processes, is noteworthy,” says Shannon Stahl, a professor of chemistry at the University of Wisconsin, who was not involved in this work. Stahl adds that “Access to salt-free aqueous solutions of H2O2 has broad implications for practical applications.”
Stahl says that “This work represents an innovative application of ‘mediated electrolysis.’ Mediated electrochemistry provides a means to merge conventional chemical processes with electrochemistry, and this is a particularly compelling demonstration of this concept. … There are many potential applications of this concept.” |
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