Author: Julie Pryor

Optogenetics with SOUL

by Sabbi Lall |

Optogenetics has revolutionized neurobiology, allowing researchers to use light to activate or deactivate neurons that are genetically modified to express a light-sensitive channel. This ability to manipulate neuron activity has allowed causal testing of the function of specific neurons, and also has therapeutic potential to reduce symptoms in brain disorders. However, activating neurons deep within a given brain, especially a large primate brain but even a small mouse brain, is challenging and currently requires implanting fibers that could cause damage or inflammation.

McGovern Investigator Guoping Feng and colleagues have now overcome this challenge, developing optogenetic tools that allow non-invasive stimulation of neurons in the deep brain.

“Neuroscientists have dreamed of methods to turn neurons on and off, to understand the function of different neurons, but also to repair brain malfunctions that lead to psychiatric disorders, and optogenetics made this possible” explained Feng, the James W. (1963) and Patricia T. Poitras Professor in Brain and Cognitive Sciences. “We were trying to improve the light sensitivity of optogenetic tools to broaden applications.”

Engineering with light

In order to stimulate neurons with minimal invasiveness, Feng and colleagues engineered a new type of opsin. The original breakthrough optogenetics protocol used channelrhodopsin, a light-sensitive channel discovered in algae. By expressing this channel in neurons, light of the right wavelength can be used to activate the neuron in a dish or in vivo. However, in vivo application requires the implantation of optical fibers to deliver the light close to the specific brain region being stimulated, especially if the target region is in the deep brain. In addition, if the neuron being targeted is in the deep brain, it is hard for light to reach the region in the absence of invasive tools that can damage tissue and impact the behavior of the animal.

Our study creates a method that can activate any mouse brain region, independent of its location, non-invasively.

“Prior to our study, a few studies have contributed in various ways to the development of optogenetic stimulation methods that would be minimally invasive to the brain. However, all of these studies had various limitations in the extent of brain regions they could activate,” said co-senior study author Robert Desimone, director of the McGovern Institute and the Doris and Don Berkey Professor of Neuroscience at MIT.

Probing the brain with SOUL

Feng and colleagues turned instead to new opsins, in particular SOUL, a new type of opsin that is very sensitive to even low-level light. The Feng group engineered this opsin, based on SSFO a second generation optogenetics tool, to have increased light sensitivity, and took advantage of a second property: that SOUL is activated in multiple steps, and once activated, it stays active for longer than other commonly used opsins. This means that a burst of a few seconds of low-level light can cause neurons to stay active for 10-30 minutes.

In order to put SOUL through its paces, the Feng lab expressed this channel in the lateral hypothalamus of the mouse brain. This is a deep region, challenging to reach with light, but with neurons that have clear functions that will lead to changes in behavior. Feng’s group was able to turn on this region non-invasively with light from outside the skull, and cause changes in feeding behavior.

“We were really surprised that SOUL was able to activate one of the deepest areas in the mouse brain, the lateral hypothalamus, which is 6 mm deep,” explains Feng.

But there were more surprises. When the authors activated a region of the primate brain using SOUL, they saw oscillations, waves of synchronized neuronal activity coming together like a choir. Such waves are believed to be important for many brain functions, and this result suggests that the new opsin can manipulate these brain waves, allowing scientists to study their role in the brain.

The authors are planning to move the study in several directions, studying models of brain disorders to identify circuits that may be suitable targets for therapy, as well as moving the methodology so that it can be used beyond the superficial cortex in larger animals. While it is too early to discuss applying the system to humans, the research brings us one step closer to future treatment of neurological disorders.

Family members unite to fight COVID-19

by Sugandha Sharma |

Even before MIT sent out its first official announcement about the COVID-19 crisis, I had already asked permission from my supervisor and taken my computer home so that I could start working from home.

My first and foremost concern was my family and friends. I was born and brought up in India, and then immigrated to Canada, so I have a big and wonderful family spread across both those countries. These countries had a lower number of COVID-19 cases at the time, but I could see what would be coming their way. I was anxious, very anxious. In India, my dad being an anesthetist could be exposed while working in the hospital. In Canada, my uncle who is a physician could be exposed, and on top of that he lives in the same house as my grandparents who are even more vulnerable due to their age. I knew I had to do something.

We started having regular video calls as a family. My mom even led daily online yoga sessions, and the discussions that followed those sessions ensured that we didn’t feel lonely and gave us a sense of purpose. Together, we looked at the statistics in the data from China and Italy, and learned that we needed to flatten the curve due to the lack of medical resources required to meet the need of the hour. We could foresee that more infections would lead to more patients, thus raising the demand for medical resources beyond the amount we had available.

We had several discussions around developing products for helping medical professionals and the general public during this pandemic.

We learned that since no government has enough resources to cope at the time of pandemics, we have to be innovative in trying to make the best use of the limited resources available to us.

Through our discussions and experiences of some of us in the field, we came to the conclusion that the only way to effectively fight COVID-19 is prevention at source. Hence, we started working on a mobile app that uses AI and advanced data analytics to trace contact, determine the risk of infection, and thereby suggest precautions. Luckily we have engineers and computer scientists in our family (my own background is in electrical engineering), so it was easy for us to divide the work.  In our prototype, when people sign-up, they are asked to fill out a short self-assessment form that can be used to identify any symptoms of COVID-19. This data is then used to predict vulnerable areas and to give recommendations to people who might have taken a certain route as shown below.

Sharma’s mobile app showing heatmap of the vulnerable areas in a locality in Toronto, ON (left) and personalized recommendations based on the most recent route taken by an individual (right).

We ended up submitting our proposal and prototype to the COVID-19 challenge launched by Vale (a global mining company) and the winners will be announced in May.

Personally, to be completely honest, I had my times when I broke down due to everything that was going on in the world around me. It’s not easy to see people dying, and losing jobs. My way of staying strong was to make sure that I was doing my best to contribute.

I have set up a beautiful home office for myself and I am focusing on my PhD research, being grateful that I can still continue to do it from home. I have also restarted the joint MIT-Harvard computational neuroscience journal club meetings online, so that members can get access to this wonderful community once again! It was amazing to see from a poll we conducted that 92% of the members of the club wanted the meetings to be re-started online.

These times are unprecedented for my generation, my mom’s generation and even for my grandmother’s generation. I have never seen the world come together in a way I have seen during this pandemic. The kind of response we have seen from our societies and governments across the globe shows that we can make intelligent decisions for the collective good of humanity. For once, we’re all on the same side!

Sugandha (Su) Sharma is a graduate student in the labs of Ila Fiete and Josh Tenenbaum. When she’s not developing a mobile app to fight COVID-19, Su explores the computational and theoretical principles underlying higher level cognition and intelligence in the human brain.

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Saxe Lab examines social impact of COVID-19

by Julie Pryor |

After being forced to relocate from their MIT dorms during the COVID19 crisis, two members of the Saxe lab are now applying their psychology skills to study the impact of mandatory relocation and social isolation on mental health.

“When ‘social distancing’ measures hit MIT, we tried to process how the implementation of these policies would impact the landscape of our social lives,” explains graduate student Heather Kosakowski, who conceived of the study late one evening with undergraduate Michelle Hung.  This landscape is broad, examining the effects of being uprooted and physically relocated from a place, but also changes in social connections, including friendships and even dating life.

MIT undergrad Michelle Hung in the Saxe lab. Photo: Michelle Hung

“I started speculating about how my life and the lives of other MIT students would change,” says Hung. “I was overwhelmed, sad, and scared. But then we realized that we were actually equipped to find the answers to our questions by conducting a study.”

Together, Kosakowski and Hung developed a survey to measure how the social behavior of MIT students, postdocs, and staff is changing over the course of the pandemic. Survey questions were designed to measure loneliness and other aspects of mental health. The survey was sent to members of the MIT community and shared on social media in mid-March, when the pandemic hit the US, and MIT made the unprecedented decision to send students home, shift to online instruction, and dramatically ramp down operations on campus.

More than 500 people responded to the initial survey, ranging in age from 18 to 60, living in cities and countries around the world. Many but not all of those who responded were affiliated with MIT. Kosakowski and Hung are sending follow-up surveys to participants every two weeks and the team plans to collect data for the duration of the pandemic.

“Throwing myself into creating the survey was a way to cope with feeling sad about leaving a community I love,” explains Hung, who flew home to California in March and admits that she struggles with feelings of loneliness now that she’s off campus.

Although it is too soon to form any conclusions about their research, Hung predicts that feelings of loneliness may actually diminish over the course of the pandemic.

“Humans have an impressive ability to adapt to change,” she says. “And I think in this virtual world, people will find novel ways to stay connected that we couldn’t have predicted.”

Whether we find ourselves feeling more or less lonely as this COVID-19 crisis comes to an end, both Kosakowski and Hung agree that it will fundamentally change life as we know it.

The Saxe lab is looking for more survey participants. To learn more about this study or to participate in the survey, click here.

 

Learning from social isolation

by Heather Kosakowski |

“Livia Tomova, a postdoc in the Saxe Lab, recently completed a study about social isolation and its impact on the brain. Michelle Hung and I had a lot of exposure to her research in the lab. When “social distancing” measures hit MIT, we tried to process how the implementation of these policies would impact the landscape of our social lives.

We came up with some hypotheses and agreed that the coronavirus pandemic would fundamentally change life as we know it.

So we developed a survey to measure how the social behavior of MIT students, postdocs, and staff changes over the course of the pandemic. Our study is still in its very early stages, but it has been an incredibly fulfilling experience to be a part of Michelle’s development as a scientist.

Heather Kosakowski’s daughter in Woods Hole, Massachusetts. Photo: Heather Kosakowski

After the undergraduates left, graduate students were also strongly urged to leave graduate student housing. My daughter (age 11) and I live in a 28th-floor apartment and her school was canceled. One of my advisors, Nancy Kanwisher, had a vacant apartment in Woods Hole that she offered to let lab members stay in. As more and more resources for children were being closed or shut down, I decided to take her up on the offer. Wood’s Hole is my daughter’s absolute favorite place and I feel extremely lucky to have such a generous option. My daughter has been coping really well with all of these changes.

While my research is at an exciting stage, I miss being on campus with the students from my cohort and my lab mates and my weekly in-person meetings with my advisors. One way I’ve been coping with this reality is by listening to stories of other people’s experiences. We are all human and we are all in the midst of a pandemic but, we are all experiencing the pandemic in different ways. I find the diversity of our experience intriguing. I have been fortunate to have friends write stories about their experiences, so that I can post them on my blog. I only have a handful of stories right now but, it has been really fun for me to listen, and humbling for me to share each individual’s unique experience.”

Heather Kosakowski is a graduate student in the labs of Rebecca Saxe and Nancy Kanwisher where she studies the infant brain and the developmental origins of object recognition, language, and music. Heather is also a Marine Corps veteran and single mom who manages a blog that “ties together different aspects of my experience, past and present, with the hopes that it might make someone else out there feel less alone.”

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Perspectives from a COVID-19 “essential worker”

by Steve Shannon |

“Overall, a big portion of my job has been to support our fantastic researchers during the rampdown period, so the transition has been tough. We supported the wind-down period and ensured those who did scan before the shutdown, were taking every precaution to keep all researchers and study participants safe.

I was out of the office during the first week of rampdown with an oscillating fever I kept wondering, do I have the coronavirus? I also played the “is it allergies or coronavirus” game. I struggled with my mood and motivation. My son is a nurse at the Montreal Children’s Hospital emergency room so I have also been deeply concerned about his well-being.

“I am one of the few people permitted to enter Building 46 to check on our imaging center equipment – and the experience has been surreal.”

Knowing that the McGovern Institute and MIT is doing so much to assist us with our mental well-being is comforting and very much appreciated.

Now, I am just trying to keep to a regular routine. I am one of the few people permitted to enter Building 46 to do equipment checks. Recently, our original magnet (MRI scanner) had a spontaneous quench, or loss of liquid helium, so I am working with engineers to get current flowing back to the magnet.

I have entered the building three times in two weeks, and each time there has been zero traffic. The parking garage is almost empty and there is parking available on the street – which never happens in Cambridge! When I see someone on the street, we look at each other in disbelief and shock. Our building is clearly in lockdown; all the doors are locked and I rarely see another person.

When this crisis is over, I most look forward to seeing people smile again — or maybe I just look forward to seeing people!

Steve Shannon has been working at the McGovern Institute since 2006, serving as operations manager of the Martinos Imaging Center for more than fourteen years.​

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Finding connections during social isolation

by Halie Olson |

“It’s been really heartening to see the compassion that’s emerged during this situation. People are looking out for each other, and thinking about each other, and checking in with each other.

Usually our social interactions are just built into the day, and now we need to be more deliberate.

The need for human connection has become so apparent these last few weeks as we’ve all been physically distancing. Usually our social interactions are just built into the day, and now we need to be more deliberate.

I’ve started writing a letter to a different person every day – something that I never took the time to do before! Especially as scientists, communication and collaboration are central to what we do. I’ve been amazed at how quickly we’re adapting to this situation and finding ways to keep connecting with each other – whether it’s virtual conferences or Zoom lab meetings or Slack channels. Plus seeing other people’s pets has been a bonus!

Overall I’ve just been really grateful and awed to see people come together, and support each other, and keep things moving forward during a tough time.”

Halie Olson, a graduate student in the labs of John Gabrieli and Rebecca Saxe, studies how early life experiences and environments impact brain development.

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Bridging the gap between clinicians and engineers

by MJ Antonini |

“Two weeks ago I joined the Greater Boston Pandemic Fabrication group (PanFab) which is coordinated by the Harvard MIT Center for Regulatory Science and has close connections with Brigham and Women’s Hospital.

My motivation for joining the PanFab group stemmed from my growing frustration with not being able to help with the current pandemic.

While following the various volunteers’ initiatives that aim to address the shortage of personal protective equipment (PPE), I felt that my training in medical engineering and medical physics in the Harvard-MIT Program in Health Sciences and Technology would be useful for interfacing clinicians at the hospital and engineers and hobbyists designing replacement solutions.

PanFab was established to meet urgent demands for medical supplies and equipment arising from the COVID19 pandemic. We have several initiatives ongoing such as 3d-printed nasopharyngeal swabs, face-shield for healthcare workers, and investigation of multiple PPE sterilization methods.

Personally, I focus on the face-shield project and am leading its production scale-up, and dissemination to local hospitals.

If anyone would like to volunteer their skills with us, send an email to panfabteam@gmail.com, we are always looking for new volunteers!”

McGovern Graduate Fellow MJ Antonini works on the improvement of polymer fibers for neural recording and stimulation in the lab of Polina Anikeeva. 

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Finding balance with physical exercise

by Anna Ivanova |

“I was never good at working out. Every time I was about to go to the gym, I would always come up with an excuse to postpone the workout. Last winter break, however, my sister introduced me to some YouTube fitness classes, and I actually had fun doing them with her. I realized that, to me, working out in my living room was much more enjoyable that dragging my feet to the gym.

Just like in the lab, [my advisor] encourages us to do our very best but is always respectful of our limits.

When COVID hit, I knew I had to do something to keep me in shape, now that I was spending all my days on the couch. I signed up for Wellbeats,  an online class platform that MIT offers [as part of its virtual fitness offerings]. Soon, I was doing their online workouts almost every day. Some of the time, I am joined by my roommates. The workouts provide a great way for us to bond, take a break from work, and relieve some of the stress that tends to build up so quickly these days.

More recently, my advisor Ev Fedorenko has started to lead her own workouts for the lab over Zoom. She carefully walks us through every exercise, showing how to do it correctly. Just like in the lab, she encourages us to do our very best but is always respectful of our limits. So, not only am I the most fit I’ve ever been in my life, but I’ve also been able to connect with my lab in a new and meaningful way.”

Anna Ivanova is a graduate student who studies how the brain processes language in the labs of Evelina Fedorenko and Nancy Kanwisher. She is also an editor and regular contributor to the MIT Grad Blog.

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3 Questions: Omar Abudayyeh and Jonathan Gootenberg on COVID-19 tests

by Julie Pryor |

One key to stopping the spread of COVID-19 is knowing who has it. A delay in reliable tests and COVID-19 diagnostics in the US has unfortunately painted an unreliable picture of just how many people are infected and how the epidemic is evolving. But new testing options are now becoming available and the information from these diagnostics will help guide decisions and actions important for public health.

To find out more about the current state of COVID-19 testing, we contacted McGovern Institute Fellows, Omar Abuddayeh and Jonathan Gootenberg, who have been developing CRISPR technologies to rapidly diagnose COVID-19 and other infectious diseases.

Q: How do COVID-19 tests work?

A. There are three main types of tests:

1) Detection of nucleic acid. These tests directly test for the RNA genome of the virus in a variety of sample types, such as nasopharyngeal swabs or sputum. These tests are most commonly performed using polymerase chain reaction (PCR), which can amplify a small part of the virus RNA sequence billions of fold higher to allow detection with a fluorescence measuring instrument. These types of tests are highly sensitive, allowing for early detection of the virus days after infection. PCR tests require complex instrumentation and are usually performed by skilled personnel in an advanced laboratory setting. An alternative method is SHERLOCK, a nucleic acid based test that does not need complex instrumentation and can be read out using a paper strip akin to a pregnancy test, without any loss of sensitivity or specificity. The test is also low cost and can be performed in less than an hour. Because of these features, we are hoping to gain FDA approval that allows deployment at the point of care or at home testing with our COVID-19 SHERLOCK test kit.

2) Detection of viral proteins. Some tests use a paper strip that have antibodies against COVID-19 proteins. These allow for easy detection of the virus in less than an hour but are at least a million-fold less sensitive than nucleic acid based tests because there is no amplification step. This makes them less ideal for screening purposes as many patients will not have enough viral load in sputum or swabs and will receive false negative results.

3) Serology tests detecting antibodies against the virus. These tests can also be used as a paper strip with antibodies that detect other antibodies that develop in someone’s blood in response to COVID-19 infection. Antibodies do not show up in blood until 1-2 weeks after symptoms present, so these tests are not great for catching infection at early stages. Serology tests are more useful for determining if someone has had the infection, recovered, and developed immunity. They may serve a purpose for finding immune people and deciding whether they can go back to work, or for developing antibody-based therapies.

Q. Why aren’t there more COVID-19 tests available?

A. The difficulties in getting nucleic acid detection tests stem from a confluence of multiple factors, including limited supplies of tests, limited supplies of other consumables needed for testing (such as nasal swabs or RNA purification kits), insufficient testing bandwidth at sites that can perform tests (often due to bottlenecks in labor or instruments), and complications behind the logistics of assigning tests or reporting back results. Therefore, just producing more testing material would not solve the issue outright, and either more instrumentation and labor is required, or newer, more rapid tests need to be developed that can be performed in a more distributed manner with reduced dependence on equipment, centralized labs, or RNA purification kits.

Q. What kind of COVID-19 test are you developing now?

A. We are working on a nucleic acid-based test that does not require complex instrumentation, rapidly returns results (with a goal of under one hour), and can be performed at a point-of-care location without trained professionals. We hope to accomplish this using a combination of techniques. First we are incorporating isothermal amplification technologies, which, unlike current PCR-based tests, do not require intricate heating and cooling to operate. We are combining this with our CRISPR-based diagnostics, allowing for sensitive detection and readout in a simple visual format, akin to a pregnancy test. We hope that this test will significantly lower the barrier for accurate diagnosis and provide another approach for COVID-19 surveillance.

Rising to the challenge

by Bob Desimone |

Dear members and friends of the McGovern Institute,

I am writing to you under unprecedented circumstances. Rather than walking through the vast atrium of our building, stopping to talk with researchers about their work, I am at home, as are many of you. The last couple of weeks have been a whirlwind as we downsized personnel within the institute from 100% to 10% capacity. Thank you tremendously to everybody that helped this huge transition to go smoothly.

As the dust settles, what is striking is how we are all still finding ways to connect. Faculty meetings have resumed, and have included vibrant discussions. Grants are still being written, and processed by the excellent finance team, and papers are being published. In addition, some of our researchers have turned their attention to COVID-19. To name a few, Feng Zhang is not only continuing to develop SHERLOCK, his CRISPR-based diagnostic, to rapidly detect the novel coronavirus. He also just released the How We Feel app with Ben Silbermann, CEO of Pinterest, and a team of global researchers. This app will allow symptom tracking and researchers to ask pressing questions about the symptoms and progression of the virus. McGovern Fellows, Omar Abudayyeh and Jonathan Gootenberg, are also working on rapid COVID-19 diagnostics.

Other researchers are mobilizing to bring their knowledge and skills to mitigate some of the unexpected shortages. Jill Crittenden, a research scientist in the Graybiel lab, has been working with a consortium to gather and curate information about the three main approaches for decontaminating N95 face masks. Shortages of these masks are causing health workers to resort to reusing these masks. The consortium has put together a website and a document that help hospitals and other frontline organizations to quickly, easily examine the effectiveness of, and use, different decontamination protocols. Michael Wells, a former graduate student in Guoping Feng‘s lab has been collaborating to set up a database where researchers that want to volunteer to help can offer up their skills.

Labs are also look at the effects of the response to COVID-19. Rebecca Saxe is working to understand some of the effects of social isolation. Her lab recently posted their findings indicating that loneliness in social isolation leads to neural craving responses similar to hunger. Also from the Saxe lab, Heather Kosakowski and Michelle Hung are also examining the effects of social isolation.

We also have a new page on our website that features stories from members of the McGovern community who have risen to the challenge during this pandemic. I have been so heartened to read about the ways in which our members are supporting one another during this unprecedented time.

But those not working directly on COVID-19 have also greatly impressed me. The diligent, efficient, and calm way in which everybody responded to help to wind down research will help us to ramp up quickly when the time comes, and it will come. In the meantime, please be assured that my team and I are here to help however is needed. If you are a researcher, we are still here to support your communications, grant submissions, and resolve logistical issues that may come up.

If you are interested in following our research, continue to stay tuned as excellent research continues to emerge. And if you are one of the Friends and donors that has come forward to support our research, thank you. Indeed, thank you to all readers for everything that you do to support the research missions of the McGovern Institute. Wishing all the best to you and your families at this difficult time,

 

Bob Desimone
Director