Category: Building 68

Improving biology education here, there, and everywhere

At the cutting edge of pedagogy, Mary Ellen Wiltrout has shaped blended and online learning at MIT and beyond.

Samantha Edelen | Department of Biology
September 18, 2024

When she was a child, Mary Ellen Wiltrout PhD ’09 didn’t want to follow in her mother’s footsteps as a K-12 teacher. Growing up in southwestern Pennsylvania, Wiltrout was studious with an early interest in science — and ended up pursuing biology as a career.

But following her doctorate at MIT, she pivoted toward education after all. Now, as the director of blended and online initiatives and a lecturer with the Department of Biology, she’s shaping biology pedagogy at MIT and beyond.

Establishing MOOCs at MIT

To this day, E.C. Whitehead Professor of Biology and Howard Hughes Medical Institute (HHMI) investigator emeritus Tania Baker considers creating a permanent role for Wiltrout one of the most consequential decisions she made as department head.

Since launching the very first MITxBio massive online open course 7.00x (Introduction to Biology – the Secret of Life) with professor of biology Eric Lander in 2013, Wiltrout’s team has worked with MIT Open Learning and biology faculty to build an award-winning repertoire of MITxBio courses.

MITxBio is part of the online learning platform edX, established by MIT and Harvard University in 2012, which today connects 86 million people worldwide to online learning opportunities. Within MITxBio, Wiltrout leads a team of instructional staff and students to develop online learning experiences for MIT students and the public while researching effective methods for learner engagement and course design.

“Mary Ellen’s approach has an element of experimentation that embodies a very MIT ethos: applying rigorous science to creatively address challenges with far-reaching impact,” says Darcy Gordon, instructor of blended and online initiatives.

Mentee to motivator

Wiltrout was inspired to pursue both teaching and research by the late geneticist Elizabeth “Beth” Jones at Carnegie Mellon University, where Wiltrout earned a degree in biological sciences and served as a teaching assistant in lab courses.

“I thought it was a lot of fun to work with students, especially at the higher level of education, and especially with a focus on biology,” Wiltrout recalls, noting she developed her love of teaching in those early experiences.

Though her research advisor at the time discouraged her from teaching, Jones assured Wiltrout that it was possible to pursue both.

Jones, who received her postdoctoral training with late Professor Emeritus Boris Magasanik at MIT, encouraged Wiltrout to apply to the Institute and join American Cancer Society and HHMI Professor Graham Walker’s lab. In 2009, Wiltrout earned a PhD in biology for thesis work in the Walker lab, where she continued to learn from enthusiastic mentors.

“When I joined Graham’s lab, everyone was eager to teach and support a new student,” she reflects. After watching Walker aid a struggling student, Wiltrout was further affirmed in her choice. “I knew I could go to Graham if I ever needed to.”

After graduation, Wiltrout taught molecular biology at Harvard for a few years until Baker facilitated her move back to MIT. Now, she’s a resource for faculty, postdocs, and students.

“She is an incredibly rich source of knowledge for everything from how to implement the increasingly complex tools for running a class to the best practices for ensuring a rigorous and inclusive curriculum,” says Iain Cheeseman, the Herman and Margaret Sokol Professor of Biology and associate head of the biology department.

Stephen Bell, the Uncas and Helen Whitaker Professor of Biology and instructor of the Molecular Biology series of MITxBio courses, notes Wiltrout is known for staying on the “cutting edge of pedagogy.”

“She has a comprehensive knowledge of new online educational tools and is always ready to help any professor to implement them in any way they wish,” he says.

Gordon finds Wiltrout’s experiences as a biologist and learning engineer instrumental to her own professional development and a model for their colleagues in science education.

“Mary Ellen has been an incredibly supportive supervisor. She facilitates a team environment that centers on frequent feedback and iteration,” says Tyler Smith, instructor for pedagogy training and biology.

Prepared for the pandemic, and beyond

Wiltrout believes blended learning, combining in-person and online components, is the best path forward for education at MIT. Building personal relationships in the classroom is critical, but online material and supplemental instruction are also key to providing immediate feedback, formative assessments, and other evidence-based learning practices.

“A lot of people have realized that they can’t ignore online learning anymore,” Wiltrout noted during an interview on The Champions Coffee Podcast in 2023. That couldn’t have been truer than in 2020, when academic institutions were forced to suddenly shift to virtual learning.

“When Covid hit, we already had all the infrastructure in place,” Baker says. “Mary Ellen helped not just our department, but also contributed to MIT education’s survival through the pandemic.”

For Wiltrout’s efforts, she received a COVID-19 Hero Award, a recognition from the School of Science for staff members who went above and beyond during that extraordinarily difficult time.

“Mary Ellen thinks deeply about how to create the best learning opportunities possible,” says Cheeseman, one of almost a dozen faculty members who nominated her for the award.

Recently, Wiltrout expanded beyond higher education and into high schools, taking on several interns in collaboration with Empowr, a nonprofit organization that teaches software development skills to Black students to create a school-to-career pipeline. Wiltrout is proud to report that one of these interns is now a student at MIT in the class of 2028.

Looking forward, Wiltrout aims to stay ahead of the curve with the latest educational technology and is excited to see how modern tools can be incorporated into education.

“Everyone is pretty certain that generative AI is going to change education,” she says. “We need to be experimenting with how to take advantage of technology to improve learning.”

Ultimately, she is grateful to continue developing her career at MIT biology.

“It’s exciting to come back to the department after being a student and to work with people as colleagues to produce something that has an impact on what they’re teaching current MIT students and sharing with the world for further reach,” she says.

As for Wiltrout’s own daughter, she’s declared she would like to follow in her mother’s footsteps — a fitting symbol of Wiltrout’s impact on the future of education.

News Brief: Lamason Lab uncovers seven novel effectors in Rickettsia parkeri infection

The enemy within: new research reveals insights into the arsenal Rickettsia parkeri uses against its host

Lillian Eden | Department of Biology
July 29, 2024

Identifying secreted proteins is critical to understanding how obligately intracellular pathogens hijack host machinery during infection, but identifying them is akin to finding a needle in a haystack.

For then-graduate student Allen Sanderlin, PhD ’24, the first indication that a risky, unlikely project might work was cyan, tic tac-shaped structures seen through a microscope — proof that his bacterial pathogen of interest was labeling its own proteins.  

Sanderlin, a member of the Lamason Lab in the Department of Biology at MIT, studies Rickettsia parkeri, a less virulent relative of the bacterial pathogen that causes Rocky Mountain Spotted Fever, a sometimes severe tickborne illness. No vaccine exists and definitive tests to diagnose an infection by Rickettsia are limited.

Rickettsia species are tricky to work with because they are obligately intracellular pathogens whose entire life cycles occur exclusively inside cells. Many approaches that have advanced our understanding of other bacterial infections and how those pathogens interact with their host aren’t applicable to Rickettsia because they can’t be grown on a plate in a lab setting. 

In a paper recently published in Nature Communications, the Lamason Lab outlines an approach for labeling and isolating R. parkeri proteins released during infection. This research reveals seven previously unknown secreted factors, known as effectors, more than doubling the number of known effectors in R. parkeri. 

Better-studied bacteria are known to hijack the host’s machinery via dozens or hundreds of secreted effectors, whose roles include manipulating the host cell to make it more susceptible to infection. However, finding those effectors in the soup of all other materials within the host cell is akin to looking for a needle in a haystack, with an added twist that researchers aren’t even sure what those needles look like for Rickettsia.  

Approaches that worked to identify the six previously known secreted effectors are limited in their scope. For example, some were found by comparing pathogenic Rickettsia to nonpathogenic strains of the bacteria, or by searching for proteins with domains that overlap with effectors from better-studied bacteria. Predictive modeling, however, relies on proteins being evolutionarily conserved. 

“Time and time again, we keep finding that Rickettsia are just weird — or, at least, weird compared to our understanding of other bacteria,” says Sanderlin, the paper’s first author. “This labeling tool allows us to answer some really exciting questions about rickettsial biology that weren’t possible before.”

The cyan tic tacs

To selectively label R. parkeri proteins, Sanderlin used a method called cell-selective bioorthogonal non-canonical amino acid tagging. BONCAT was first described in research from the Tirrell Lab at Caltech. The Lamason Lab, however, is the first group to use the tool successfully in an obligate intracellular bacterial pathogen; the thrilling moment when Sanderlin saw cyan tic-tac shapes indicated successfully labeling only the pathogen, not the host. 

Sanderlin next used an approach called selective lysis, carefully breaking open the host cell while leaving the pathogen, filled with labeled proteins, intact. This allowed him to extract proteins that R. parkeri had released into its host because the only labeled proteins amid other host cell material were effectors the pathogen had secreted. 

Sanderlin had successfully isolated and identified seven needles in the haystack, effectors never before identified in Rickettsia biology. The novel secreted rickettsial factors are dubbed SrfA, SrfB, SrfC, SrfD, SrfE, SrfF, and SrfG. 

“Every grad student wants to be able to name something,” Sanderlin says. “The most exciting — but frustrating — thing was that these proteins don’t look like anything we’ve seen before.”

Special delivery

Theoretically, Sanderlin says, once the effectors are secreted, they work independently from the bacteria — a driver delivering a pizza does not need to check back in with the store at every merge or turn.

Since SrfA-G didn’t resemble other known effectors or host proteins the pathogen could be mimicking during infection, Sanderlin then tried to answer some basic questions about their behavior. Where the effectors localize, meaning where in the cell they go, could hint at their purpose and what further experiments could be used to investigate it. 

To determine where the effectors were going, Sanderlin added the effectors he’d found to uninfected cells by introducing DNA that caused human cell lines to express those proteins. The experiment succeeded: he discovered that different Srfs went to different places throughout the host cells.  

SrfF and SrfG are found throughout the cytoplasm, whereas SrfB localizes to the mitochondria. That was especially intriguing because its structure is not predicted to interact with or find its way to the mitochondria, and the organelle appears unchanged despite the presence of the effector. 

Further, SrfC and SrfD found their way to the endoplasmic reticulum. The ER would be especially useful for a pathogen to appropriate, given that it is a dynamic organelle present throughout the cell and has many essential roles, including synthesizing proteins and metabolizing lipids. 

Aside from where effectors localize, knowing what they may interact with is critical. Sanderlin showed that SrfD interacts with Sec61, a protein complex that delivers proteins across the ER membrane. In keeping with the theme of the novelty of Sanderlin’s findings, SrfD does not resemble any proteins known to interact with the ER or Sec61. 

With this tool, Sanderlin identified novel proteins whose binding partners and role during infection can now be studied further. 

“These results are exciting but tantalizing,” Sanderlin says. “What Rickettsia secrete — the effectors, what they are, and what they do is, by and large, still a black box.” 

There are very likely other effectors in the proverbial cellular haystack. Sanderlin found that SrfA-G are not found in every species of Rickettsia, and his experiments were solely conducted with Rickettsia at late stages of infection — earlier windows of time may make use of different effectors. This research was also carried out in human cell lines, so there may be an entirely separate repertoire of effectors in ticks, which are responsible for spreading the pathogen.

Expanding Tool Development

Becky Lamason, the senior author of the Nature Communications paper, noted that this tool is one of a few avenues the lab is exploring to investigate R. parkeri, including a paper in the Journal of Bacteriology on conditional genetic manipulation. Characterizing how the pathogen behaves with or without a particular effector is leaps and bounds ahead of where the field was just a few years ago when Sanderlin was Lamason’s first graduate student to join the lab.

“What I always hoped for in the lab is to push the technology, but also get to the biology. These are two of what will hopefully be a suite of ways to attack this problem of understanding how these bacteria rewire and manipulate the host cell,” Lamason says. “We’re excited, but we’ve only scratched the surface.”

Brady Weissbourd named Searle Scholar

With an eye on regenerative medicine, Weissbourd's lab will study how jellyfish manage to constantly integrate new neurons into their nervous system.

David Orenstein | The Picower Institute for Learning and Memory
July 8, 2024

Scientists who dream of a future in which regenerative medicine has advanced enough to enable repairs in human nervous systems currently have more questions than answers. As a recently named Searle Scholar, MIT Assistant Professor Brady Weissbourd will seek to learn some of the needed fundamentals by studying a master of neural regeneration: the jellyfish, Clytia hemisphaerica.

Weissbourd, a faculty member in the Department of Biology and The Picower Institute for Learning and Memory, has helped to pioneer use of the seafaring species in neuroscience research for many reasons. It is transparent for easy imaging, reproduces rapidly, and shares many basic nervous system properties with mammals despite diverging evolutionarily 600 million years ago (just after the development of the earliest nervous systems). Meanwhile, with about 10,000 neurons, the jellyfish fills a gap in the field in terms of that degree of complexity.

But what Weissbourd didn’t appreciate until he began experimenting with the jellyfish was that they are also incredibly good at refreshing and rebuilding their nervous systems with new cells. After becoming the first researcher to develop the ability to genetically manipulate the organism, he started teasing out how its highly distributed nervous system (there is no central brain), was organized to enable its many behaviors. When he ablated a subnetwork of cells to test whether it was indeed responsible for a particular feeding behavior, he found that within a week it had completely regrown. Moreover, he has observed that the jellyfish constantly produce and integrate new cells, even in the absence of major injury.

Looking for the logic

The finding raised a proverbial boatload of intriguing questions that his support of $100,000 a year for the next three years from the Searle Scholars Program will help him pursue.

“Where are these newborn neurons coming from in both the normal and regenerative contexts?” Weissbourd asked. “What rules guide them to the correct locations to rebuild these networks, both to integrate these newborn neurons into the network without messing it up and also to recreate it during regeneration? Are the rules the same or different between these contexts?”

Additionally, by using a combination of techniques such as imaging neural activity during behavior, sequencing gene expression cell by cell, and computational modeling, Weissbourd’s lab has discerned that within their web-like mesh of neurons, jellyfish harbor more than a dozen different functional subnetworks that enable its variety of different behaviors. Can all the subnetworks regenerate? If not, why do some forgo the remarkable ability? Among those that do regenerate, do they all do so the same way? If they employ different means, then learning what those are could provide multiple answers to the question of how new neurons can successfully integrate into existing neural networks.

Building on support provided by a Klingenstein-Simons Fellowship Weissbourd earned last year, he’ll be able to pursue experiments designed to understand the “logic” of how jellyfish manage neural regeneration.

“The ability to understand how nervous systems regenerate has significant implications for regenerative medicine,” Weissbourd said.

A complete 3D ‘wiring diagram’

As part of the new award, Weissbourd also plans to create a major new resource for jellyfish neurobiology to advance not only this project, but also the research of any other scientist who wants to study the organism. Working with collaborator Jeff Lichtman, a professor of molecular and cellular biology at Harvard University, Weissbourd will create a complete 3D reconstruction of a jellyfish’s nervous system at the subcellular resolution enabled by electron microscopy. The resource, which Weissbourd plans to provide openly online, will amount to a full “wiring diagram” of a jellyfish where every circuit connection can be mapped.

Being able to see how every neural circuit is constructed in a whole animal will enable Weissbourd to answer questions about how the circuits are built and therefore how new neurons integrate. Having a complete and detailed view of every circuit will improve the computational models his lab is building to predict how anatomy helps give rise to function and behavior. And given that new neurons are being born, migrating and integrating all the time, Weissbourd said, the imaging will also likely yield a snapshot of neural regeneration in action in its many stages.

Weissbourd said he was grateful for the honor of being named a Searle Scholar, which not only provides support for his lab’s work, but also welcomes him into a new community of young scientists.

“I’m honored and super excited,” Weissbourd said. “I’m excited to interact with the other scholars as well.”

 

Sara Prescott named Pew Scholar in the Biomedical Sciences

Assistant Professor Sara Prescott and her lab plan to test whether and how neurons have a role in airway remodeling, which goes awry in many diseases.

David Orenstein | The Picower Institute for Learning and Memory
June 17, 2024