#Institute for Medical Engineering and Science (IMES)

[jcmarchi]

A two-dose schedule could make HIV vaccines more effective

New Post has been published on https://thedigitalinsider.com/a-two-dose-schedule-could-make-hiv-vaccines-more-effective/

A two-dose schedule could make HIV vaccines more effective

One major reason why it has been difficult to develop an effective HIV vaccine is that the virus mutates very rapidly, allowing it to evade the antibody response generated by vaccines.

Several years ago, MIT researchers showed that administering a series of escalating doses of an HIV vaccine over a two-week period could help overcome a part of that challenge by generating larger quantities of neutralizing antibodies. However, a multidose vaccine regimen administered over a short time is not practical for mass vaccination campaigns.

In a new study, the researchers have now found that they can achieve a similar immune response with just two doses, given one week apart. The first dose, which is much smaller, prepares the immune system to respond more powerfully to the second, larger dose.

This study, which was performed by bringing together computational modeling and experiments in mice, used an HIV envelope protein as the vaccine. A single-dose version of this vaccine is now in clinical trials, and the researchers hope to establish another study group that will receive the vaccine on a two-dose schedule.

“By bringing together the physical and life sciences, we shed light on some basic immunological questions that helped develop this two-dose schedule to mimic the multiple-dose regimen,” says Arup Chakraborty, the John M. Deutch Institute Professor at MIT and a member of MIT’s Institute for Medical Engineering and Science and the Ragon Institute of MIT, MGH and Harvard University.

This approach may also generalize to vaccines for other diseases, Chakraborty notes.

Chakraborty and Darrell Irvine, a former MIT professor of biological engineering and materials science and engineering and member of the Koch Institute for Integrative Cancer Research, who is now a professor of immunology and microbiology at the Scripps Research Institute, are the senior authors of the study, which appears today in Science Immunology. The lead authors of the paper are Sachin Bhagchandani PhD ’23 and Leerang Yang PhD ’24.

Neutralizing antibodies

Each year, HIV infects more than 1 million people around the world, and some of those people do not have access to antiviral drugs. An effective vaccine could prevent many of those infections. One promising vaccine now in clinical trials consists of an HIV protein called an envelope trimer, along with a nanoparticle called SMNP. The nanoparticle, developed by Irvine’s lab, acts as an adjuvant that helps recruit a stronger B cell response to the vaccine.

In clinical trials, this vaccine and other experimental vaccines have been given as just one dose. However, there is growing evidence that a series of doses is more effective at generating broadly neutralizing antibodies. The seven-dose regimen, the researchers believe, works well because it mimics what happens when the body is exposed to a virus: The immune system builds up a strong response as more viral proteins, or antigens, accumulate in the body.

In the new study, the MIT team investigated how this response develops and explored whether they could achieve the same effect using a smaller number of vaccine doses.

“Giving seven doses just isn’t feasible for mass vaccination,” Bhagchandani says. “We wanted to identify some of the critical elements necessary for the success of this escalating dose, and to explore whether that knowledge could allow us to reduce the number of doses.”

The researchers began by comparing the effects of one, two, three, four, five, six, or seven doses, all given over a 12-day period. They initially found that while three or more doses generated strong antibody responses, two doses did not. However, by tweaking the dose intervals and ratios, the researchers discovered that giving 20 percent of the vaccine in the first dose and 80 percent in a second dose, seven days later, achieved just as good a response as the seven-dose schedule.

“It was clear that understanding the mechanisms behind this phenomenon would be crucial for future clinical translation,” Yang says. “Even if the ideal dosing ratio and timing may differ for humans, the underlying mechanistic principles will likely remain the same.”

Using a computational model, the researchers explored what was happening in each of these dosing scenarios. This work showed that when all of the vaccine is given as one dose, most of the antigen gets chopped into fragments before it reaches the lymph nodes. Lymph nodes are where B cells become activated to target a particular antigen, within structures known as germinal centers.

When only a tiny amount of the intact antigen reaches these germinal centers, B cells can’t come up with a strong response against that antigen.

However, a very small number of B cells do arise that produce antibodies targeting the intact antigen. So, giving a small amount in the first dose does not “waste” much antigen but allows some B cells and antibodies to develop. If a second, larger dose is given a week later, those antibodies bind to the antigen before it can be broken down and escort it into the lymph node. This allows more B cells to be exposed to that antigen and eventually leads to a large population of B cells that can target it.

“The early doses generate some small amounts of antibody, and that’s enough to then bind to the vaccine of the later doses, protect it, and target it to the lymph node. That’s how we realized that we don’t need to give seven doses,” Bhagchandani says. “A small initial dose will generate this antibody and then when you give the larger dose, it can again be protected because that antibody will bind to it and traffic it to the lymph node.”

T-cell boost

Those antigens may stay in the germinal centers for weeks or even longer, allowing more B cells to come in and be exposed to them, making it more likely that diverse types of antibodies will develop.

The researchers also found that the two-dose schedule induces a stronger T-cell response. The first dose activates dendritic cells, which promote inflammation and T-cell activation. Then, when the second dose arrives, even more dendritic cells are stimulated, further boosting the T-cell response.

Overall, the two-dose regimen resulted in a fivefold improvement in the T-cell response and a 60-fold improvement in the antibody response, compared to a single vaccine dose.

“Reducing the ‘escalating dose’ strategy down to two shots makes it much more practical for clinical implementation. Further, a number of technologies are in development that could mimic the two-dose exposure in a single shot, which could become ideal for mass vaccination campaigns,” Irvine says.

The researchers are now studying this vaccine strategy in a nonhuman primate model. They are also working on specialized materials that can deliver the second dose over an extended period of time, which could further enhance the immune response.

The research was funded by the Koch Institute Support (core) Grant from the National Cancer Institute, the National Institutes of Health, and the Ragon Institute of MIT, MGH, and Harvard.

[mit]

An implantable device could enable injection-free control of diabetes

The device contains encapsulated cells that produce insulin, plus a tiny oxygen-producing factory that keeps the cells healthy.

Anne Trafton | MIT News

One promising approach to treating Type 1 diabetes is implanting pancreatic islet cells that can produce insulin when needed, which can free patients from giving themselves frequent insulin injections. However, one major obstacle to this approach is that once the cells are implanted, they eventually run out of oxygen and stop producing insulin.

To overcome that hurdle, MIT engineers have designed a new implantable device that not only carries hundreds of thousands of insulin-producing islet cells, but also has its own on-board oxygen factory, which generates oxygen by splitting water vapor found in the body.

The researchers showed that when implanted into diabetic mice, this device could keep the mice’s blood glucose levels stable for at least a month. The researchers now hope to create a larger version of the device, about the size of a stick of chewing gum, that could eventually be tested in people with Type 1 diabetes.

“You can think of this as a living medical device that is made from human cells that secrete insulin, along with an electronic life support-system. We’re excited by the progress so far, and we really are optimistic that this technology could end up helping patients,” says Daniel Anderson, a professor in MIT’s Department of Chemical Engineering, a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES), and the senior author of the study.

While the researchers’ main focus is on diabetes treatment, they say that this kind of device could also be adapted to treat other diseases that require repeated delivery of therapeutic proteins.

MIT Research Scientist Siddharth Krishnan is the lead author of the paper, which appears today in the Proceedings of the National Academy of Sciences. The research team also includes several other researchers from MIT, including Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute, as well as researchers from Boston Children’s Hospital.

Replacing injections

Most patients with Type 1 diabetes have to monitor their blood glucose levels carefully and inject themselves with insulin at least once a day. However, this process doesn’t replicate the body’s natural ability to control blood glucose levels.

“The vast majority of diabetics that are insulin-dependent are injecting themselves with insulin, and doing their very best, but they do not have healthy blood sugar levels,” Anderson says. “If you look at their blood sugar levels, even for people that are very dedicated to being careful, they just can’t match what a living pancreas can do.”

A better alternative would be to transplant cells that produce insulin whenever they detect surges in the patient’s blood glucose levels. Some diabetes patients have received transplanted islet cells from human cadavers, which can achieve long-term control of diabetes; however, these patients have to take immunosuppressive drugs to prevent their body from rejecting the implanted cells.

More recently, researchers have shown similar success with islet cells derived from stem cells, but patients who receive those cells also need to take immunosuppressive drugs.

Another possibility, which could prevent the need for immunosuppressive drugs, is to encapsulate the transplanted cells within a flexible device that protects the cells from the immune system. However, finding a reliable oxygen supply for these encapsulated cells has proven challenging.

Some experimental devices, including one that has been tested in clinical trials, feature an oxygen chamber that can supply the cells, but this chamber needs to be reloaded periodically. Other researchers have developed implants that include chemical reagents that can generate oxygen, but these also run out eventually.

The MIT team took a different approach that could potentially generate oxygen indefinitely, by splitting water. This is done using a proton-exchange membrane — a technology originally deployed to generate hydrogen in fuel cells — located within the device. This membrane can split water vapor (found abundantly in the body) into hydrogen, which diffuses harmlessly away, and oxygen, which goes into a storage chamber that feeds the islet cells through a thin, oxygen-permeable membrane.

A significant advantage of this approach is that it does not require any wires or batteries. Splitting this water vapor requires a small voltage (about 2 volts), which is generated using a phenomenon known as resonant inductive coupling. A tuned magnetic coil located outside the body transmits power to a small, flexible antenna within the device, allowing for wireless power transfer. It does require an external coil, which the researchers anticipate could be worn as a patch on the patient’s skin.

Drugs on demand

After building their device, which is about the size of a U.S. quarter, the researchers tested it in diabetic mice. One group of mice received the device with the oxygen-generating, water-splitting membrane, while the other received a device that contained islet cells without any supplemental oxygen. The devices were implanted just under the skin, in mice with fully functional immune systems.

The researchers found that mice implanted with the oxygen-generating device were able to maintain normal blood glucose levels, comparable to healthy animals. However, mice that received the nonoxygenated device became hyperglycemic (with elevated blood sugar) within about two weeks.

Typically when any kind of medical device is implanted in the body, attack by the immune system leads to a buildup of scar tissue called fibrosis, which can reduce the devices’ effectiveness. This kind of scar tissue did form around the implants used in this study, but the device’s success in controlling blood glucose levels suggests that insulin was still able to diffuse out of the device, and glucose into it.

This approach could also be used to deliver cells that produce other types of therapeutic proteins that need to be given over long periods of time. In this study, the researchers showed that the device could also keep alive cells that produce erythropoietin, a protein that stimulates red blood cell production.

“We’re optimistic that it will be possible to make living medical devices that can reside in the body and produce drugs as needed,” Anderson says. “There are a variety of diseases where patients need to take proteins exogenously, sometimes very frequently. If we can replace the need for infusions every other week with a single implant that can act for a long time, I think that could really help a lot of patients.”

The researchers now plan to adapt the device for testing in larger animals and eventually humans. For human use, they hope to develop an implant that would be about the size of a stick of chewing gum. They also plan to test whether the device can remain in the body for longer periods of time.

“The materials we’ve used are inherently stable and long-lived, so I think that kind of long-term operation is within the realm of possibility, and that’s what we’re working on,” Krishnan says.

“We are very excited about these findings, which we believe could provide a whole new way of someday treating diabetes and possibly other diseases,” Langer adds.

The research was funded by JDRF, the Leona M. and Harry B. Helmsley Charitable Trust, and the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health.

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[educationinvaranasi]

Education in varanasi

Varanasi, often referred to as the cultural capital of India, holds a significant place in the realm of education as well. Let's delve into why education in Varanasi is notable:

Rich Cultural and Historical Background

Varanasi, situated on the banks of the sacred river Ganges, has been a center of learning for centuries. The city is steeped in history, with its ancient universities and traditional Gurukuls (educational institutions) attracting scholars and students from all over the world.

Educational Institutions

Banaras Hindu University (BHU):

Founded in 1916 by Pandit Madan Mohan Malaviya, BHU is one of the largest residential universities in Asia.

It offers a wide range of courses in various disciplines such as arts, sciences, engineering, medicine, and management.

BHU is known for its emphasis on research and has produced many distinguished alumni who have made significant contributions in their respective fields.

Institute of Medical Sciences (IMS), BHU:

Renowned for its medical education and research facilities, IMS BHU is a leading institution in the field of healthcare.

Mahatma Gandhi Kashi Vidyapith (MGKV):

Founded by Mahatma Gandhi during the freedom struggle, MGKV focuses on promoting Gandhian ideals and values through education.

It offers courses in arts, commerce, sciences, and vocational studies.

Traditional and Modern Blend

Varanasi not only preserves its ancient educational traditions but also embraces modern educational methods and technologies. Institutions like BHU and MGKV blend traditional knowledge with contemporary academic practices, providing students with a holistic educational experience.

Cultural Influence on Education

The cultural milieu of Varanasi fosters an environment conducive to learning and intellectual growth. The city's vibrant cultural heritage, including music, dance, art, and religious practices, adds a unique dimension to the educational experience.

Challenges and Opportunities

While Varanasi boasts of rich educational heritage, challenges such as infrastructure development, quality of education delivery, and inclusivity remain. Efforts are underway to address these issues and further enhance Varanasi's status as a hub of education and learning.

Conclusion

Education in Varanasi is not just about acquiring academic knowledge; it's about immersing oneself in a cultural and spiritual journey. The city continues to attract students and scholars seeking to explore its rich tapestry of knowledge and tradition. As Varanasi evolves, its educational institutions strive to uphold its legacy while embracing the future of learning.

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[sunaleisocial]

Ian Waitz named vice president for research

New Post has been published on https://sunalei.org/news/ian-waitz-named-vice-president-for-research/

Ian Waitz named vice president for research

In a letter to the MIT community today, President Sally Kornbluth announced the appointment of Ian A. Waitz to the position of vice president for research. In the role, Waitz will report to the president and oversee MIT’s vast research enterprise. The appointment is effective May 1.

Waitz, who is also the Jerome C. Hunsaker Professor of Aeronautics and Astronautics, brings deep knowledge of MIT to the position. Over more than 30 years, he has served in a wide range of roles across the Institute, where he has made his mark through energy, optimism, persistence, and a commitment to MIT’s mission of using education and innovation to create a better world.

“Ian brings a rare range and depth of understanding of MIT’s research and educational enterprise, our daily operations, our institutional challenges and opportunities, our history and our values — and an unmatched record of solving hard problems and getting big, high-stakes things done well,” Kornbluth wrote. 

“MIT’s research enterprise is a critical part of our mission, not just for the impact that innovation and discovery have on the world, but also for the way it enables us to educate people by giving them problems that no one else has ever solved before,” Waitz says. “That builds a sort of intellectual capacity and resilience to work on really hard problems, and the nation and the world need us to work on hard problems.”

Waitz will step down from his current role as vice chancellor overseeing undergraduate and graduate education, where he was instrumental in advancing the priorities of the Chancellor’s Office, currently led by Melissa Nobles.

In that role, which he has held since 2017, Waitz worked with students, faculty, and staff from across the Institute to revamp the first-year undergraduate academic experience, helped steer the Institute through the Covid-19 pandemic, and led efforts to respond to graduate student unionization. Waitz also led a strategic restructuring to integrate the former offices of the Dean for Undergraduate Education and the Dean for Graduate Education, creating the Office of the Vice Chancellor and leading to a more aligned and efficient organization. And, he spearheaded projects to expand professional development opportunities for graduate students, created the MIT Undergraduate Advising Center, worked to significantly expand undergraduate financial aid, and broadly expanded support for graduate students.

“I think my experience gives me a unique perspective on research and education at MIT,” Waitz says. “Education is obviously an amazing part of MIT, and working with students bridges education and the research. That’s one of the things that’s special about a research university. I’m excited for this new role and to continue to work to further strengthen MIT’s exceptional research enterprise.”

Waitz will be filling a role previously held by Maria Zuber, the E. A. Griswold Professor of Geophysics, who now serves as MIT’s presidential advisor for science and technology policy. Waitz says he’s eager to dive in and work to identify ways to help MIT’s prolific research engine run more smoothly. The move is just the latest example of Waitz leaning into new opportunities in service to MIT.

Prior to assuming his current role as vice chancellor, Waitz served as the dean of the School of Engineering between 2011 and 2017, supporting the school’s ability to attract and support exceptional students and faculty. He oversaw the launch of programs including the Institute for Data, Systems, and Society (IDSS), the Institute for Medical Engineering and Science (IMES), the Sandbox Innovation Fund, and the MIT Beaver Works program with Lincoln Laboratory. He also strengthened co-curricular and enrichment programs for undergraduate and graduate students, and worked with department heads to offer more flexible degrees.

Prior to that, Waitz served as the head of MIT’s Department of Aeronautics and Astronautics, where he has been a faculty member since 1991. His research focuses on developing technological, operational, and policy options to mitigate the environmental impacts of aviation. He is a member of the National Academy of Engineering, a fellow of the American Institute of Aeronautics and Astronautics, and has worked closely with industry and government throughout his career.

“One lesson I’ve learned is that the greatest strength of MIT is our students, faculty, and staff,” Waitz says. “We identify people who are real intellectual entrepreneurs. Those are the people that really thrive here, and what you want to do is create a low-friction, high-resource environment for them. Amazing things bubble up from that.”

[moremedtech]

MIT engineers design a robotic replica of the heart’s right chamber

MIT engineers design a robotic replica of the heart’s right chamber. The realistic model could aid the development of better heart implants and shed light on understudied heart disorders. Robotic Replica - A ballet of beats A heart’s shelf-life December 08, 2023 - MIT engineers have created a robotic replica of the right ventricle of the heart that mimics the beating and blood-pumping action of a living heart. The robo-ventricle is made up of real heart tissue and synthetic, balloon-like artificial muscles that allow scientists to control the ventricle's contractions while also observing how its natural valves and other intricate structures work. The artificial ventricle can be programmed to simulate both healthy and diseased states. The researchers manipulated the model to simulate right ventricular dysfunction conditions such as pulmonary hypertension and myocardial infarction. The model was also used to test cardiac devices. For example, the researchers implanted a mechanical valve to repair a naturally malfunctioning valve, then observed how the ventricle's pumping changed as a result. They claim that the new robotic right ventricle, or RRV, can be used as a realistic platform for studying right ventricle disorders and testing devices and therapies to treat them. “The right ventricle is particularly susceptible to dysfunction in intensive care unit settings, especially in patients on mechanical ventilation,” says Manisha Singh, a postdoc at MIT’s Institute for Medical Engineering and Science (IMES). “The RRV simulator can be used in the future to study the effects of mechanical ventilation on the right ventricle and to develop strategies to prevent right heart failure in these vulnerable patients.” Singh and her colleagues report details of the new design in an open-access paper appearing today in Nature Cardiovascular Research. Her co-authors include Associate Professor Ellen Roche, who is a core member of IMES and the associate head for research in the Department of Mechanical Engineering at MIT; along with Jean Bonnemain, Caglar Ozturk, Clara Park, Diego Quevedo-Moreno, Meagan Rowlett, and Yiling Fan of MIT; Brian Ayers of Massachusetts General Hospital; Christopher Nguyen of Cleveland Clinic; and Mossab Saeed of Boston Children’s Hospital.

Robotic Replica - A ballet of beats

The right ventricle is one of the heart’s four chambers, along with the left ventricle and the left and right atria. Of the four chambers, the left ventricle is the heavy lifter, as its thick, cone-shaped musculature is built for pumping blood through the entire body. The right ventricle, Roche says, is a “ballerina” in comparison, as it handles a lighter though no-less-crucial load. “The right ventricle pumps deoxygenated blood to the lungs, so it doesn’t have to pump as hard,” Roche notes. “It’s a thinner muscle, with more complex architecture and motion.” This anatomical complexity has made it difficult for clinicians to accurately observe and assess right ventricle function in patients with heart disease. “Conventional tools often fail to capture the intricate mechanics and dynamics of the right ventricle, leading to potential misdiagnoses and inadequate treatment strategies,” Singh says To improve understanding of the lesser-known chamber and speed the development of cardiac devices to treat its dysfunction, the team designed a realistic, functional model of the right ventricle that both captures its anatomical intricacies and reproduces its pumping function. The model includes real heart tissue, which the team chose to incorporate because it retains natural structures that are too complex to reproduce synthetically. “There are thin, tiny chordae and valve leaflets with different material properties that are all moving in concert with the ventricle’s muscle. Trying to cast or print these very delicate structures is quite challenging,” Roche explains

A heart’s shelf-life

In the new study, the team reports explanting a pig’s right ventricle, which they treated to carefully preserve its internal structures. They then fit a silicone wrapping around it, which acted as a soft, synthetic myocardium, or muscular lining. Within this lining, the team embedded several long, balloon-like tubes, which encircled the real heart tissue, in positions that the team determined through computational modeling to be optimal for reproducing the ventricle’s contractions. The researchers connected each tube to a control system, which they then set to inflate and deflate each tube at rates that mimicked the heart’s real rhythm and motion. To test its pumping ability, the team infused the model with a liquid similar in viscosity to blood. This particular liquid was also transparent, allowing the engineers to observe with an internal camera how internal valves and structures responded as the ventricle pumped liquid through. They found that the artificial ventricle’s pumping power and the function of its internal structures were similar to what they previously observed in live, healthy animals, demonstrating that the model can realistically simulate the right ventricle’s action and anatomy. The researchers could also tune the frequency and power of the pumping tubes to mimic various cardiac conditions, such as irregular heartbeats, muscle weakening, and hypertension. “We’re reanimating the heart, in some sense, and in a way that we can study and potentially treat its dysfunction,” Roche says To show that the artificial ventricle can be used to test cardiac devices, the team surgically implanted ring-like medical devices of various sizes to repair the chamber’s tricuspid valve — a leafy, one-way valve that lets blood into the right ventricle. When this valve is leaky, or physically compromised, it can cause right heart failure or atrial fibrillation, and leads to symptoms such as reduced exercise capacity, swelling of the legs and abdomen, and liver enlargement. The researchers surgically manipulated the robo-ventricle’s valve to simulate this condition, then either replaced it by implanting a mechanical valve or repaired it using ring-like devices of different sizes. They observed which device improved the ventricle’s fluid flow as it continued to pump. “With its ability to accurately replicate tricuspid valve dysfunction, the RRV serves as an ideal training ground for surgeons and interventional cardiologists,” Singh says. “They can practice new surgical techniques for repairing or replacing the tricuspid valve on our model before performing them on actual patients.” Currently, the RRV can simulate realistic function over a few months. The team is working to extend that performance and enable the model to run continuously for longer stretches. They are also working with designers of implantable devices to test their prototypes on the artificial ventricle and possibly speed their path to patients. And looking far in the future, Roche plans to pair the RRV with a similar artificial, functional model of the left ventricle, which the group is currently fine-tuning. “We envision pairing this with the left ventricle to make a fully tunable, artificial heart, that could potentially function in people,” Roche says. “We’re quite a while off, but that’s the overarching vision.” This research was supported, in part, by the National Science Foundation. Source: MIT Read the full article

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[reportwire]

Collin Stultz named co-director and MIT lead of the Harvard-MIT Program in Health Sciences and Technology | MIT News

Collin Stultz named co-director and MIT lead of the Harvard-MIT Program in Health Sciences and Technology | MIT News

Collin M. Stultz, the Nina T. and Robert H. Rubin Professor in Medical Engineering and Science at MIT, has been named co-director of the Harvard-MIT Program in Health Sciences and Technology (HST), and associate director of MIT’s Institute for Medical Engineering and Science (IMES), effective June 1. IMES is HST’s home at MIT. Stultz is a professor of electrical engineering and computer science…

[polyolefinprince]

i didn't know you were doing that ask game omg, do any 3 of your choosing that you havent answered yet but you want to! (mainly because im too lazy to pull up the question list)

I know everything about me so idk what y'all would wanna know so I'm just gonna give three facts about my past, present, and future (that tbh anybody that knows me irl knows but y'all don't know me irl so it's fair)

When I was 3 I swallowed a battery or penny or something and it burned a hole in my intestines so I was hospitalized for like a month, during which time due to constantly throwing up I had to get several teeth removed and to get easier access they surgically widened my mouth (which I've never heard any complaints about). Then two years later when I was 5, my intestines wound up in a knot as a post-surgery complication. My mom wanted me to go into a medical field but I spent enough time in the hospital as a kid that I couldn't.

I've always been super into extracurricular activities! In high school I ran cross country for a couple years before quitting because I was too slow, but then I went on to do drama club (both props and stagehand as well as acting at different points), student council (I was historian which recorded all events for a big book), key club (community service, I was treasurer), National Honor Society (also community service, I was also treasurer), French club (I was president). Then I came to college and joined house council (I just wanted to plan parties, but I ended up treasurer again freshman year), the chemistry club, the American Institute of Chemical Engineers, and oSTEM (for queer people in science, I'm going on my second year as president now).

My goal in life is to work as an R&D engineer somewhere in the Northeast (not Western Mass, but maybe Boston or New York or PA) working on implementing sustainability in polymer science. I want at least a dog, maybe two and maybe a cat. Ideally I'm married in this future, but my hopes are low. Assuming I am married, I lean more towards not having kids. At some point I want to retire relatively early (a combo of engineering salary and no kids helps with that) and turn my baking hobby into minor income.

This isn't what you asked for but now y'all know a lot more about me, for better or for worse.

[materialsscienceandengineering]

MIT Engineers Create an Inhalable Form of Messenger RNA

Messenger RNA, which can induce cells to produce therapeutic proteins, holds great promise for treating a variety of diseases. The biggest obstacle to this approach so far has been finding safe and efficient ways to deliver mRNA molecules to the target cells.

In an advance that could lead to new treatments for lung disease, MIT researchers have now designed an inhalable form of mRNA. This aerosol could be administered directly to the lungs to help treat diseases such as cystic fibrosis, the researchers say.

“We think the ability to deliver mRNA via inhalation could allow us to treat a range of different diseases of the lung,” says Daniel Anderson, an associate professor in MIT’s Department of Chemical Engineering, a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES), and the senior author of the study.

The researchers showed that they could induce lung cells in mice to produce a target protein — in this case, a bioluminescent protein. If the same success rate can be achieved with therapeutic proteins, that could be high enough to treat many lung diseases, the researchers say.

Read more.

[jcmarchi]

A new way to reprogram immune cells and direct them toward anti-tumor immunity

New Post has been published on https://thedigitalinsider.com/a-new-way-to-reprogram-immune-cells-and-direct-them-toward-anti-tumor-immunity/

A new way to reprogram immune cells and direct them toward anti-tumor immunity

A collaboration between four MIT groups, led by principal investigators Laura L. Kiessling, Jeremiah A. Johnson, Alex K. Shalek, and Darrell J. Irvine, in conjunction with a group at Georgia Tech led by M.G. Finn, has revealed a new strategy for enabling immune system mobilization against cancer cells. The work, which appears today in ACS Nano, produces exactly the type of anti-tumor immunity needed to function as a tumor vaccine — both prophylactically and therapeutically.

Cancer cells can look very similar to the human cells from which they are derived. In contrast, viruses, bacteria, and fungi carry carbohydrates on their surfaces that are markedly different from those of human carbohydrates. Dendritic cells — the immune system’s best antigen-presenting cells — carry proteins on their surfaces that help them recognize these atypical carbohydrates and bring those antigens inside of them. The antigens are then processed into smaller peptides and presented to the immune system for a response. Intriguingly, some of these carbohydrate proteins can also collaborate to direct immune responses. This work presents a strategy for targeting those antigens to the dendritic cells that results in a more activated, stronger immune response.

Tackling tumors’ tenacity

The researchers’ new strategy shrouds the tumor antigens with foreign carbohydrates and co-delivers them with single-stranded RNA so that the dendritic cells can be programmed to recognize the tumor antigens as a potential threat. The researchers targeted the lectin (carbohydrate-binding protein) DC-SIGN because of its ability to serve as an activator of dendritic cell immunity. They decorated a virus-like particle (a particle composed of virus proteins assembled onto a piece of RNA that is noninfectious because its internal RNA is not from the virus) with DC-binding carbohydrate derivatives. The resulting glycan-costumed virus-like particles display unique sugars; therefore, the dendritic cells recognize them as something they need to attack.

“On the surface of the dendritic cells are carbohydrate binding proteins called lectins that combine to the sugars on the surface of bacteria or viruses, and when they do that they penetrate the membrane,” explains Kiessling, the paper’s senior author. “On the cell, the DC-SIGN gets clustered upon binding the virus or bacteria and that promotes internalization. When a virus-like particle gets internalized, it starts to fall apart and releases its RNA.” The toll-like receptor (bound to RNA) and DC-SIGN (bound to the sugar decoration) can both signal to activate the immune response.

Once the dendritic cells have sounded the alarm of a foreign invasion, a robust immune response is triggered that is significantly stronger than the immune response that would be expected with a typical untargeted vaccine. When an antigen is encountered by the dendritic cells, they send signals to T cells, the next cell in the immune system, to give different responses depending on what pathways have been activated in the dendritic cells.

Advancing cancer vaccine development

The activity of a potential vaccine developed in line with this new research is twofold. First, the vaccine glycan coat binds to lectins, providing a primary signal. Then, binding to toll-like receptors elicits potent immune activation.

The Kiessling, Finn, and Johnson groups had previously identified a synthetic DC-SIGN binding group that directed cellular immune responses when used to decorate virus-like particles. But it was unclear whether this method could be utilized as an anticancer vaccine. Collaboration between researchers in the labs at MIT and Georgia Tech demonstrated that in fact, it could.

Valerie Lensch, a chemistry PhD student from MIT’s Program in Polymers and Soft Matter and a joint member of the Kiessling and Johnson labs, took the preexisting strategy and tested it as an anticancer vaccine, learning a great deal about immunology in order to do so.

“We have developed a modular vaccine platform designed to drive antigen-specific cellular immune responses,” says Lensch. “This platform is not only pivotal in the fight against cancer, but also offers significant potential for combating challenging intracellular pathogens, including malaria parasites, HIV, and Mycobacterium tuberculosis. This technology holds promise for tackling a range of diseases where vaccine development has been particularly challenging.”

Lensch and her fellow researchers conducted in vitro experiments with extensive iterations of these glycan-costumed virus-like particles before identifying a design that demonstrated potential for success. Once that was achieved, the researchers were able to move on to an in vivo model, an exciting milestone for their research.

Adele Gabba, a postdoc in the Kiessling Lab, conducted the in vivo experiments with Lensch, and Robert Hincapie, who conducted his PhD studies with Professor M.G. Finn at Georgia Tech, built and decorated the virus-like particles with a series of glycans that were sent to him from the researchers at MIT.

“We are discovering that carbohydrates act like a language that cells use to communicate and direct the immune system,” says Gabba. “It’s thrilling that we have begun to decode this language and can now harness it to reshape immune responses.”

“The design principles behind this vaccine are rooted in extensive fundamental research conducted by previous graduate student and postdoctoral researchers over many years, focusing on optimizing lectin engagement and understanding the roles of lectins in immunity,” says Lensch. “It has been exciting to witness the translation of these concepts into therapeutic platforms across various applications.”

[bharathshan]

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Data Science Course in Mumbai

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Data Science Course in Mumbai

[sunaleisocial]

Circadian rhythms can influence drugs’ effectiveness

New Post has been published on https://sunalei.org/news/circadian-rhythms-can-influence-drugs-effectiveness/

Circadian rhythms can influence drugs’ effectiveness

Giving drugs at different times of day could significantly affect how they are metabolized in the liver, according to a new study from MIT.

Using tiny, engineered livers derived from cells from human donors, the researchers found that many genes involved in drug metabolism are under circadian control. These circadian variations affect how much of a drug is available and how effectively the body can break it down. For example, they found that enzymes that break down Tylenol and other drugs are more abundant at certain times of day.

Overall, the researchers identified more than 300 liver genes that follow a circadian clock, including many involved in drug metabolism, as well as other functions such as inflammation. Analyzing these rhythms could help researchers develop better dosing schedules for existing drugs.

“One of the earliest applications for this method could be fine-tuning drug regimens of already approved drugs to maximize their efficacy and minimize their toxicity,” says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science at MIT, and a member of MIT’s Koch Institute for Integrative Cancer Research and the Institute for Medical Engineering and Science (IMES).

The study also revealed that the liver is more susceptible to infections such as malaria at certain points in the circadian cycle, when fewer inflammatory proteins are being produced.

Bhatia is the senior author of the new study, which appears today in Science Advances. The paper’s lead author is Sandra March, a research scientist in IMES.

Metabolic cycles

It is estimated that about 50 percent of human genes follow a circadian cycle, and many of these genes are active in the liver. However, exploring how circadian cycles affect liver function has been difficult because many of these genes are not identical in mice and humans, so mouse models can’t be used to study them.

Bhatia’s lab has previously developed a way to grow miniaturized livers using liver cells called hepatocytes, from human donors. In this study, she and her colleagues set out to investigate whether these engineered livers have their own circadian clocks.

Working with Charles Rice’s group at Rockefeller University, they identified culture conditions that support the circadian expression of a clock gene called Bmal1. This gene, which regulates the cyclic expression of a wide range of genes, allowed the liver cells to develop synchronized circadian oscillations. Then, the researchers measured gene expression in these cells every three hours for 48 hours, enabling them to identify more than 300 genes that were expressed in waves.

Most of these genes clustered in two groups — about 70 percent of the genes peaked together, while the remaining 30 percent were at their lowest point when the others peaked. These included genes involved in a variety of functions, including drug metabolism, glucose and lipid metabolism, and several immune processes.

Once the engineered livers established these circadian cycles, the researchers could use them to explore how circadian cycles affect liver function. First, they set out to study how time of day would affect drug metabolism, looking at two different drugs — acetaminophen (Tylenol) and atorvastatin, a drug used to treat high cholesterol.

When Tylenol is broken down in the liver, a small fraction of the drug is converted into a toxic byproduct known as NAPQI. The researchers found that the amount of NAPQI produced can vary by up to 50 percent, depending on what time of day the drug is administered. They also found that atorvastatin generates higher toxicity at certain times of day.

Both of these drugs are metabolized in part by an enzyme called CYP3A4, which has a circadian cycle. CYP3A4 is involved in processing about 50 percent of all drugs, so the researchers now plan to test more of those drugs using their liver models.

“In this set of drugs, it will be helpful to identify the time of the day to administer the drug to reach the highest effectiveness of the drug and minimize the adverse effects,” March says.

The MIT researchers are now working with collaborators to analyze a cancer drug they suspect may be affected by circadian cycles, and they hope to investigate whether this may also be true of drugs used in pain management.

Susceptibility to infection

Many of the liver genes that show circadian behavior are involved in immune responses such as inflammation, so the researchers wondered if this variation might influence susceptibility to infection. To answer that question, they exposed the engineered livers to Plasmodium falciparum, a parasite that causes malaria, at different points in the circadian cycle.

These studies revealed that the livers were more likely to become infected after exposure at different times of day. This is due to variations in the expression of genes called interferon-stimulated genes, which help to suppress infections.

“The inflammatory signals are much stronger at certain times of days than others,” Bhatia says. “This means that a virus like hepatitis or parasite like the one that causes malaria might be better at taking hold in your liver at certain times of the day.”

The researchers believe this cyclical variation may occur because the liver dampens its response to pathogens following meals, when it is typically exposed to an influx of microorganisms that might trigger inflammation even if they are not actually harmful.

Bhatia’s lab is now taking advantage of these cycles to study infections that are usually difficult to establish in engineered livers, including malaria infections caused by parasites other than Plasmodium falciparum.

“This is quite important for the field, because just by setting up the system and choosing the right time of infection, we can increase the infection rate of our culture by 25 percent, enabling drug screens that were otherwise impractical,” March says.

The research was funded by the MIT International Science and Technology Initiatives MIT-France program, the Koch Institute Support (core) Grant from the U.S. National Cancer Institute, the National Institute of Health and Medical Research of France, and the French National Research Agency.

[reportwire]

Collin Stultz named co-director and MIT lead of the Harvard-MIT Program in Health Sciences and Technology | MIT News

Collin Stultz named co-director and MIT lead of the Harvard-MIT Program in Health Sciences and Technology | MIT News

Collin M. Stultz, the Nina T. and Robert H. Rubin Professor in Medical Engineering and Science at MIT, has been named co-director of the Harvard-MIT Program in Health Sciences and Technology (HST), and associate director of MIT’s Institute for Medical Engineering and Science (IMES), effective June 1. IMES is HST’s home at MIT. Stultz is a professor of electrical engineering and computer science…

[shuga-hill]

Artificial intelligence yields new antibiotic

A deep-learning model identifies a powerful new drug that can kill many species of antibiotic-resistant bacteria.

Anne Trafton | MIT News Office

Using a machine-learning algorithm, MIT researchers have identified a powerful new antibiotic compound. In laboratory tests, the drug killed many of the world’s most problematic disease-causing bacteria, including some strains that are resistant to all known antibiotics. It also cleared infections in two different mouse models.

The computer model, which can screen more than a hundred million chemical compounds in a matter of days, is designed to pick out potential antibiotics that kill bacteria using different mechanisms than those of existing drugs.

“We wanted to develop a platform that would allow us to harness the power of artificial intelligence to usher in a new age of antibiotic drug discovery,” says James Collins, the Termeer Professor of Medical Engineering and Science in MIT’s Institute for Medical Engineering and Science (IMES) and Department of Biological Engineering. “Our approach revealed this amazing molecule which is arguably one of the more powerful antibiotics that has been discovered.”

In their new study, the researchers also identified several other promising antibiotic candidates, which they plan to test further. They believe the model could also be used to design new drugs, based on what it has learned about chemical structures that enable drugs to kill bacteria.

“The machine learning model can explore, in silico, large chemical spaces that can be prohibitively expensive for traditional experimental approaches,” says Regina Barzilay, the Delta Electronics Professor of Electrical Engineering and Computer Science in MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL).

Barzilay and Collins, who are faculty co-leads for MIT’s Abdul Latif Jameel Clinic for Machine Learning in Health (J-Clinic), are the senior authors of the study, which appears today in Cell. The first author of the paper is Jonathan Stokes, a postdoc at MIT and the Broad Institute of MIT and Harvard.

A new pipeline

Over the past few decades, very few new antibiotics have been developed, and most of those newly approved antibiotics are slightly different variants of existing drugs. Current methods for screening new antibiotics are often prohibitively costly, require a significant time investment, and are usually limited to a narrow spectrum of chemical diversity.

“We’re facing a growing crisis around antibiotic resistance, and this situation is being generated by both an increasing number of pathogens becoming resistant to existing antibiotics, and an anemic pipeline in the biotech and pharmaceutical industries for new antibiotics,” Collins says.

To try to find completely novel compounds, he teamed up with Barzilay, Professor Tommi Jaakkola, and their students Kevin Yang, Kyle Swanson, and Wengong Jin, who have previously developed machine-learning computer models that can be trained to analyze the molecular structures of compounds and correlate them with particular traits, such as the ability to kill bacteria.

The idea of using predictive computer models for “in silico” screening is not new, but until now, these models were not sufficiently accurate to transform drug discovery. Previously, molecules were represented as vectors reflecting the presence or absence of certain chemical groups. However, the new neural networks can learn these representations automatically, mapping molecules into continuous vectors which are subsequently used to predict their properties.

In this case, the researchers designed their model to look for chemical features that make molecules effective at killing E. coli. To do so, they trained the model on about 2,500 molecules, including about 1,700 FDA-approved drugs and a set of 800 natural products with diverse structures and a wide range of bioactivities.

Once the model was trained, the researchers tested it on the Broad Institute’s Drug Repurposing Hub, a library of about 6,000 compounds. The model picked out one molecule that was predicted to have strong antibacterial activity and had a chemical structure different from any existing antibiotics. Using a different machine-learning model, the researchers also showed that this molecule would likely have low toxicity to human cells.

This molecule, which the researchers decided to call halicin, after the fictional artificial intelligence system from “2001: A Space Odyssey,” has been previously investigated as possible diabetes drug. The researchers tested it against dozens of bacterial strains isolated from patients and grown in lab dishes, and found that it was able to kill many that are resistant to treatment, including Clostridium difficile, Acinetobacter baumannii, and Mycobacterium tuberculosis. The drug worked against every species that they tested, with the exception of Pseudomonas aeruginosa, a difficult-to-treat lung pathogen.

To test halicin’s effectiveness in living animals, the researchers used it to treat mice infected with A. baumannii, a bacterium that has infected many U.S. soldiers stationed in Iraq and Afghanistan. The strain of A. baumannii that they used is resistant to all known antibiotics, but application of a halicin-containing ointment completely cleared the infections within 24 hours.

Preliminary studies suggest that halicin kills bacteria by disrupting their ability to maintain an electrochemical gradient across their cell membranes. This gradient is necessary, among other functions, to produce ATP (molecules that cells use to store energy), so if the gradient breaks down, the cells die. This type of killing mechanism could be difficult for bacteria to develop resistance to, the researchers say.

“When you’re dealing with a molecule that likely associates with membrane components, a cell can’t necessarily acquire a single mutation or a couple of mutations to change the chemistry of the outer membrane. Mutations like that tend to be far more complex to acquire evolutionarily,” Stokes says.

In this study, the researchers found that E. coli did not develop any resistance to halicin during a 30-day treatment period. In contrast, the bacteria started to develop resistance to the antibiotic ciprofloxacin within one to three days, and after 30 days, the bacteria were about 200 times more resistant to ciprofloxacin than they were at the beginning of the experiment.

The researchers plan to pursue further studies of halicin, working with a pharmaceutical company or nonprofit organization, in hopes of developing it for use in humans.

Optimized molecules

After identifying halicin, the researchers also used their model to screen more than 100 million molecules selected from the ZINC15 database, an online collection of about 1.5 billion chemical compounds. This screen, which took only three days, identified 23 candidates that were structurally dissimilar from existing antibiotics and predicted to be nontoxic to human cells.

In laboratory tests against five species of bacteria, the researchers found that eight of the molecules showed antibacterial activity, and two were particularly powerful. The researchers now plan to test these molecules further, and also to screen more of the ZINC15 database.

The researchers also plan to use their model to design new antibiotics and to optimize existing molecules. For example, they could train the model to add features that would make a particular antibiotic target only certain bacteria, preventing it from killing beneficial bacteria in a patient’s digestive tract.

“This groundbreaking work signifies a paradigm shift in antibiotic discovery and indeed in drug discovery more generally,” says Roy Kishony, a professor of biology and computer science at Technion (the Israel Institute of Technology), who was not involved in the study. “Beyond in silica screens, this approach will allow using deep learning at all stages of antibiotic development, from discovery to improved efficacy and toxicity through drug modifications and medicinal chemistry.”

The research was funded by the Abdul Latif Jameel Clinic for Machine Learning in Health, the Defense Threat Reduction Agency, the Broad Institute, the DARPA Make-It Program, the Canadian Institutes of Health Research, the Canadian Foundation for Innovation, the Canada Research Chairs Program, the Banting Fellowships Program, the Human Frontier Science Program, the Pershing Square Foundation, the Swiss National Science Foundation, a National Institutes of Health Early Investigator Award, the National Science Foundation Graduate Research Fellowship Program, and a gift from Anita and Josh Bekenstein.

Topics: ResearchBiological engineeringElectrical Engineering & Computer Science (eecs)Institute for Medical Engineering and Science (IMES)Computer Science and Artificial Intelligence Laboratory (CSAIL)Broad InstituteSchool of EngineeringBacteriaMicrobesMedicineHealthMachine learningArtificial intelligenceAlgorithmsJ-ClinicNational Institutes of Health (NIH)National Science Foundation (NSF)

[irvinpressler]

Covid-19 Diagnostic Based on MIT Technology Might be tested on Patient Samples Soon

As more Covid-19 cases appear in the United States and around the world, the need for fast, easy-to-use diagnostic tests is becoming ever more pressing. A startup company spun out from MIT is now working on a paper-based test that can deliver results in under half an hour, based on technology developed at MIT’s Institute for Medical Engineering and Science (IMES). Cambridge-based E25Bio, which developed the test, is now preparing to submit it to the FDA for emergency use authorization, which would grant temporary approval for using the device on patient samples during public health emergencies.

The technology behind the new E25Bio diagnostic was developed by Lee Gehrke, the Hermann L.F. von Helmholtz Professor at IMES, and other members of his lab, including Irene Bosch, a former IMES research scientist who is now the CTO of E25Bio. The tests consist of strips of paper that are coated with antibodies that bind to a specific viral protein. A second antibody is attached to gold nanoparticles, and the patient’s sample is added to a solution of those particles. The test strip is then dipped in this solution. If the viral protein is present, it attaches to the antibodies on the paper strip as well as the nanoparticle-bound antibodies, and a colored spot appears on the strip within 20 minutes.

Continue:-

The post Covid-19 Diagnostic Based on MIT Technology Might be tested on Patient Samples Soon appeared first on Gadgets, gizmos, and tech from the East.

Covid-19 Diagnostic Based on MIT Technology Might be tested on Patient Samples Soon published first on https://greatestspeakers.tumblr.com/

[jcmarchi]

Study assesses seizure risk from stimulating the thalamus

New Post has been published on https://thedigitalinsider.com/study-assesses-seizure-risk-from-stimulating-the-thalamus/

Study assesses seizure risk from stimulating the thalamus

The idea of electrically stimulating a brain region called the central thalamus has gained traction among researchers and clinicians because it can help arouse subjects from unconscious states induced by traumatic brain injury or anesthesia, and can boost cognition and performance in awake animals. But the method, called CT-DBS, can have a side effect: seizures. A new study by researchers at MIT and Massachusetts General Hospital (MGH) who were testing the method in awake mice quantifies the probability of seizures at different stimulation currents and cautions that they sometimes occurred even at low levels.

“Understanding production and prevalence of this type of seizure activity is important because brain stimulation-based therapies are becoming more widely used,” says co-senior author Emery N. Brown, Edward Hood Taplin Professor of Medical Engineering and Computational Neuroscience in The Picower Institute for Learning and Memory, the Institute for Medical Engineering and Science, the Department of Brain and Cognitive Sciences, and the Center for Brains Minds and Machines (CBMM) at MIT.

In the brain, the seizures associated with CT-DBS occur as “electrographic seizures,” which are bursts of voltage among neurons across a broad spectrum of frequencies. Behaviorally, they manifest as “absence seizures” in which the subject appears to take on a blank stare and freezes for about 10-20 seconds.

In their study, the researchers were hoping to determine a CT-DBS stimulation current — in a clinically relevant range of under 200 microamps — below which seizures could be reliably avoided.

In search of that ideal current, they developed a protocol of starting brief bouts of CT-DBS at 1 microamp and then incrementally ramping the current up to 200 microamps until they found a threshold where an electrographic seizure occurred. Once they found that threshold, then they tested a longer bout of stimulation at the next lowest current level in hopes that an electrographic seizure wouldn’t occur. They did this for a variety of different stimulation frequencies. To their surprise, electrographic seizures still occurred 2.2 percent of the time during those longer stimulation trials (i.e. 22 times out of 996 tests) and in 10 out of 12 mice. At just 20 microamps, mice still experienced seizures in three out of 244 tests, a 1.2 percent rate.

“This is something that we needed to report because this was really surprising,” says co-lead author Francisco Flores, a research affiliate in The Picower Institute and CBMM, and an instructor in anesthesiology at MGH, where Brown is also an anesthesiologist. Isabella Dalla Betta, a technical associate in The Picower Institute, co-led the study published in Brain Stimulation.

Stimulation frequency didn’t matter for seizure risk but the rate of electrographic seizures increased as the current level increased. For instance, it happened in 5 out of 190 tests at 50 microamps, and two out of 65 tests at 100 microamps. The researchers also found that when an electrographic seizure occurred, it did so more quickly at higher currents than at lower levels. Finally, they also saw that seizures happened more quickly if they stimulated the thalamus on both sides of the brain, versus just one side. Some mice exhibited behaviors similar to absence seizure, though others became hyperactive.

It is not clear why some mice experienced electrographic seizures at just 20 microamps while two mice did not experience the seizures even at 200. Flores speculated that there may be different brain states that change the predisposition to seizures amid stimulation of the thalamus. Notably, seizures are not typically observed in humans who receive CT-DBS while in a minimally conscious state after a traumatic brain injury or in animals who are under anesthesia. Flores said the next stage of the research would aim to discern what the relevant brain states may be.

In the meantime, the study authors wrote, “EEG should be closely monitored for electrographic seizures when performing CT-DBS, especially in awake subjects.”

The paper’s co-senior author is Matt Wilson, Sherman Fairchild Professor in The Picower Institute, CBMM, and the departments of Biology and Brain and Cognitive Sciences. In addition to Dalla Betta, Flores, Brown and Wilson, the study’s other authors are John Tauber, David Schreier, and Emily Stephen.

Support for the research came from The JPB Foundation, The Picower Institute for Learning and Memory; George J. Elbaum ’59, SM ’63, PhD ’67, Mimi Jensen, Diane B. Greene SM ’78, Mendel Rosenblum, Bill Swanson, annual donors to the Anesthesia Initiative Fund; and the National Institutes of Health.