Uphill battles: Across the country in 75 days

Amulya Aluru ’23, MEng ’24 and the MIT Spokes have spent the summer spreading science, over 3,000 miles on two wheels.

Lillian Eden | Department of Biology
August 22, 2024

Amulya Aluru ’23, MEng ’24, will head to the University of California at Berkeley for a PhD in molecular and cell biology PhD this fall. Aluru knows her undergraduate 6-7 major and MEng program, where she worked on a computational project in a biology lab, have prepared her for the next step of her academic journey.

“I’m a lot more comfortable with the unknown in terms of research — and also life,” she says. “While I’ve enjoyed what I’ve done so far, I think it’s equally valuable to try and explore new topics. I feel like there’s still a lot more for me to learn in biology.”

Unlike many of her peers, however, Aluru won’t reach the San Francisco Bay Area by car, plane, or train. She will arrive by bike — a journey she began in Washington just a few days after receiving her master’s degree.

Showing that science is accessible

Spokes is an MIT-based nonprofit that each year sends students on a transcontinental bike ride. Aluru worked for months with seven fellow MIT students on logistics and planning. Since setting out, the team has bonded over their love of memes and cycling-themed nicknames: Hank “Handlebar Hank” Stennes, Clelia “Climbing Cleo” Lacarriere, Varsha “Vroom Vroom Varsha” Sandadi, Rebecca “Railtrail Rebecca” Lizarde, JD “JDerailleur Hanger” Hagood, Sophia “Speedy Sophia” Wang, Amulya “Aero Amulya” Aluru, and Jessica “Joyride Jess” Xu. The support minivan, carrying food, luggage, and occasionally injured or sick cyclists, even earned its own nickname: “Chrissy”, short for Chrysler Pacifica.

“I really wanted to do something to challenge myself, but not in a strictly academic sense,” Aluru says of her decision to join the team and bike more than 3,000 miles this summer.

The Spokes team is not biking across the country solely to accomplish such a feat. Throughout their journey, they’ll be offering a variety of science demonstrations, including making concrete with Rice Krispies, demonstrating the physics of sound, using 3D printers, and, in Aluru’s case, extracting DNA from strawberries.

“We’re going to be in a lot of really different learning environments,” she says. “I hope to demonstrate that science can be accessible, even if you don’t have a lab at your disposal.”

These demonstrations have been held in venues such as a D.C. jaila space camp, and libraries and youth centers across the country; their learning festivals were even featured on a local news channel in Kentucky.

Some derailments

The team was beset with challenges from the first day they started their journey. Aluru’s first day on the road involved driving to every bike shop and REI store in the D.C. metro area to purchase bike computers for navigation because the ones the team had already purchased would only display maps of Europe.

Four days in and four Chrysler Pacificas later — the first was unsafe due to bald tires, the second made a weird sound as they pulled out of the rental lot, and the third’s gas pedal stopped working over 50 miles away from the nearest rental agency — the team was back together again in Waynesboro, Virginia, for the first time since they’d set out.

Since then, they’ve had run-ins with local fauna — including mean dogs and a meaner turtle — attempted to repair a tubeless bike that was not, in fact, tubeless, and slept in Chrissy the minivan after their tents got soaked and blew away.

Although it hasn’t all been smooth riding, the team has made time for fun. They’ve perfected the art of eating a Clif bar while on two wheelsplayed around on monkey bars in Colorado, met up with Stanford Spokes, enjoyed pounds of ice cream, and downed gallons of lattes.

The team prioritized routes on bike trails, rather than highways, as much as possible. Their teaching activities are scheduled between visits to National Parks like Tahoe, Zion, Bryce Canyon, Arches, and touring and hiking places like Breaks Interstate ParkMammoth Cave, and the Collegiate Peaks.

Aluru says she’s excited to see parts of the country she’s never visited before, and experience the terrain under her own power — except for breaks when it’s her turn to drive Chrissy.

Rolling with the ups and downs

Aluru was only a few weeks into her first Undergraduate Research Opportunities Program project in the late professor Angelika Amon’s lab when the Covid-19 pandemic hit, quickly transforming her wet lab project into a computational one. David Waterman, her postdoc mentor in the Amon Lab, was trained as a biologist, not a computational scientist. Luckily, Aluru had just taken two computer science classes.

“I was able to have a big hand in formulating my project and bouncing ideas off of him,” she recalls. “That helped me think about scientific questions, which I was able to apply when I came back to campus and started doing wet lab research again.”

When Aluru returned to campus, she began work in the Page Lab at the Whitehead Institute for Biomedical Research. She continued working there for the rest of her time at MIT, first as an undergraduate student and then as an MEng student.

The Page Lab’s work primarily concerns sex differences and how those differences play out in genetics, development, and disease — and the Department of Electronic Engineering and Computer Science, which oversees the MEng program, allows students to pursue computational projects across disciplines, no matter the department.

For her MEng work, Aluru looked at sex differences in human height, a continuation of a paper that the Page Lab published in 2019. Height is an easily observable human trait and, from previous research, is known to be sex-biased across at least five species. Genes that have sex-biased expression patterns, or expression patterns that are higher or lower in males compared to females, may play a role in establishing or maintaining these sex differences. Through statistical genetics, Aluru replicated the findings of the earlier paper and expanded them using newly published datasets.

“Amulya has had an amazing journey in our department,” says David Page, professor of biology and core member of the Whitehead Institute. “There is simply no stopping her insatiable curiosity and zest for life.”

Working with the lab as a graduate student came with more day-to-day responsibility and independence than when she was an undergrad.

“It was a shift I quite appreciated,” Aluru says. “At times it was challenging, but I think it was a good challenge: learning how to structure my research on my own, while still getting a lot of support from lab members and my PI [principal investigator].”

Gearing up for the future

Since departing MIT, Aluru and the rest of the Spokes team have spent their nights camping, sleeping in churches, and staying with hosts. They enjoyed the longest day of the year in a surprisingly “Brooklyn chic” house, spent a lazy afternoon on a river, and pinky-promised to be in each other’s weddings. The team has also been hosted by, met up with, and run into MIT alums as they’ve crossed the country.

As Aluru looks to the future, she admits she’s not exactly sure what she’ll study — but when she reaches the West Coast, she knows she’s not leaving what she’s built through MIT far behind.

“There’s going to be a small MIT community even there — a lot of my friends are in San Francisco, and a few people I know are also going to be at Berkeley,” she says. “I have formed a community at MIT that I know will support me in all my future endeavors.”

Alumni News: Mission: Protecting the Planet

MIT Alum Catharine Conley, SB ’88, who earned two bachelor's degrees in biology and the humanities, spent more than a decade as NASA's planetary protection officer, working on protocols to prevent biological contamination on Earth and beyond.

Kathryn M. O'Neill | MIT Technology Review
August 20, 2024

When the space shuttle Columbia disintegrated during reentry in 2003, the disaster killed the human crew of seven—but not every creature onboard.

A collection of roundworms (a.k.a. nematodes) survived and was found in the debris, surprising everyone and prompting Catharine Conley ’88—principal investigator on the experiment—to publish a paper on the implications for astrobiology. It also led Conley to a new NASA role: planetary protection officer.

“Planetary protection is about trying to prevent Earth organisms from getting to other planets and, more importantly, making sure there’s nothing nasty when you bring material back to Earth,” says Conley, who held the job from 2006 to 2017 and helped ensure US compliance with the Outer Space Treaty, the international agreement that governs space exploration.

Conley got an early start on science thanks to a geneticist mother and mathematician father, and then completed two MIT majors—in biology and the humanities, focusing on Russian and French translation—and two bachelor’s degrees. That language study would prove useful: “Translation is essential when communicating with people from very different backgrounds—politicians, managers, bureaucrats, engineers, scientists—so for being planetary protection officer that was probably my most valuable training.”

After earning a PhD in plant sciences from Cornell, Conley studied a protein involved in muscle contraction as a postdoc at the Scripps Research Institute. That work led to NASA, where the Columbia experiment was designed to test the effects of low gravity on nematodes’ muscle tissue (muscle atrophy is a known problem for astronauts).

As the nematodes showed, Earth organisms are hard to kill. So a planetary protection officer must develop protocols not only to prevent biological contamination here but also to ensure that any “alien” life forms discovered elsewhere aren’t actually from Earth. “We have found signs of intelligent life on Mars,” Conley notes wryly. “But it’s us.”

Some scientists theorize that life on Earth actually came from Mars, Conley points out, which would increase the risk of importing something infectious: novel yet related organisms can quickly wreak havoc, as the recent pandemic illustrated.

Conley is currently visiting at the Carnegie Institution for Science, working to develop an analytical framework for assessing whether a space sample is indigenous life, Earth contamination, or just chemistry.

What can super-healing species teach us about regeneration?

Albert Almada PhD ’13 studies the mechanics of how stem cells rebuild tissues. “Digging deep into the science is what MIT taught me,” he says.

Lillian Eden | Department of Biology
February 21, 2024

When Albert E. Almada PhD ’13 embarks on a new project, he always considers two criteria instilled in him during his time as a graduate student in the Department of Biology at MIT.

“If you want to make a big discovery, you have to approach it from a unique perspective — a unique angle,” Almada says. “You also have to be willing to dive into the unknown and go to the leading edge of your field.”

This is not without its challenges — but with an innovative spirit, Almada says, one can find ways to apply technologies and approaches to a new area of research where a roadmap doesn’t yet exist.

Now an assistant professor of orthopedic surgery and stem cell biology and regenerative medicine at the Keck School of Medicine of the University of Southern California (USC), Almada studies the mechanics of how stem cells rebuild tissues after trauma and how stem cell principles are dysregulated and drive conditions like degenerative disease and aging, exploring these topics through an evolutionary lens.

He’s also trying to solve a mystery that has intrigued scientists for centuries: Why can some vertebrate species like fish, salamanders, and lizards regenerate entire body parts, but mammals cannot? Almada’s laboratory at USC tackles these critical questions in the musculoskeletal system.

Almada’s fascination with muscle development and regeneration can be traced back to growing up in southern California. Almada’s brother had a degenerative muscle disease called Duchenne muscular dystrophy — and, while Almada grew stronger and stronger, his brother grew weaker and weaker. Last summer, Almada’s brother, unfortunately, lost his battle with his disorder at the age of 41.

“Watching his disease progress in those early years is what inspired me to become a scientist,” Almada recalls. “Sometimes science can be personal.”

Almada went to the University of California at Irvine for his undergraduate degree, majoring in biological sciences. During his summers, he participated in the Undergraduate Research Program (URP) at the Cold Spring Harbor Laboratory and the MIT Summer Research Program-Bio (now the Bernard S. and Sophie G. Gould MIT Summer Research Program in Biology, BSG-MSRP-Bio), where he saw the passion, rigor, and drive that solidified his desire to pursue a PhD.

Despite his interest in clinical applications, skeletal muscle, and regenerative biology, Almada was drawn to the Department of Biology at MIT, which is focused on basic fundamental research.

“I was willing to bet that it all came down to understanding basic cellular processes and things going wrong with the cell and how it interacts with its environment,” he says. “The MIT biology program really helped me define an identity for myself and gave me a template for how to tackle clinical problems from a molecular perspective.”

Almada’s PhD thesis work was based on a curious finding that Phillip Sharp, Institute Professor emeritus, professor emeritus of biology, and intramural faculty at the Koch Institute for Integrative Cancer Research, had made in 2007 — that transcription, the process of copying DNA into a messenger molecule called RNA, can occur in both directions at gene promoters. In one direction, it was long understood that fully formed mRNA is transcribed and can be used as a blueprint to make a protein. The transcription Sharp observed, in the opposite direction, results in a very short RNA that is not used as a gene product blueprint.

Almada’s project dug into what those short RNA molecules are — their structure and sequence, and why they’re not produced the same way that coding messenger RNA is. In two papers published in PNAS and Nature, Almada and colleagues discovered that a balance between splicing and transcription termination signals controls the length of an RNA. This finding has wider implications because toxic RNAs are produced and can build up in several degenerative diseases; being able to splice out or shorten RNAs to remove the harmful segments could be a potential therapeutic treatment.

“That experience convinced me that if I want to make big discoveries, I have to focus on basic science,” he says. “It also gave me the confidence that if I can succeed at MIT, I can succeed just about anywhere and in any field of biology.”

At the time Almada was in graduate school, there was a lot of excitement about transcription factor reprogramming. Transcription factors are the proteins responsible for turning on essential genes that tell a cell what to be and how to behave; a subset of them can even theoretically turn one cell type into another.

Almada began to wonder whether a specialized set of transcription factors instructs stem cells to rebuild tissues after trauma. After MIT, Almada moved on to a postdoctoral position in the lab of Amy Wagers, a leader in muscle stem cell biology at Harvard University, to immerse himself in this problem.

In many tissues in our bodies, a population of stem cells typically exists in an inactive, non-dividing state called quiescence. Once activated, these stem cells interact with their environment, sense damage signals, and turn on programs of proliferation and differentiation, as well as self-renewal, which is critical to maintaining a pool of stem cells in the tissue.

One of the biggest mysteries in the field of regenerative biology is how stem cells transition from dormancy into that activated, highly regenerative state. The body’s ability to turn on stem cells, including those in the skeletal muscle system, declines as we age and is often dysregulated in degenerative diseases — diseases like the one Almada’s brother suffered from.

In a study Almada published in Cell Reports several years ago, he identified a family of transcription factors that work together to turn on a critical regenerative gene program within hours of muscle trauma. This program drives muscle stem cells out of quiescence and speeds up healing.

“Now my lab is studying this regenerative program and its potential dysregulation in aging and degenerative muscle diseases using mouse and human models,” Almada says. “We’re also drawing parallels with super-healing species like salamanders and lizards.”

Recently, Almada has been working on characterizing the molecular and functional properties of stem cells in lizards, attempting to understand how the genes and pathways differ from mammalian stem cells. Lizards can regenerate massive amounts of skeletal muscle from scratch — imagine if human muscle tissue could be regrown as seamlessly as a lizard’s tail can. He is also exploring whether the tail is unique, or if stem cells in other tissues in lizards can regenerate faster and better than the tail, by comparing analogous injuries in a mouse model.

“This is a good example of approaching a problem from a new perspective: We believe we’re going to discover new biology in lizards that we can use to enhance skeletal muscle growth in vulnerable human populations, including those that suffer from deadly muscle disorders,” Almada says.

In just three years of starting his faculty position at USC, his work and approach have already received recognition in academia, with junior faculty awards from the Baxter Foundation and the Glenn Foundation/American Federation of Aging Research. He also received his first RO1 award from the National Institutes of Health with nearly $3 million in funding. Almada and his first graduate student, Alma Zuniga Munoz, were also awarded the HHMI Gilliam Fellowship last summer. Zuniga Munoz is the first to be recognized with this award at USC; fellowship recipients, student and advisor pairs, are selected with the goal of preparing students from underrepresented groups for leadership roles in science.

Almada himself is a second-generation Mexican American and has been involved in mentoring and training throughout his academic career. He was a graduate resident tutor for Spanish House at MIT and currently serves as the chair of the Diversity, Equity, and Inclusion Committee in the Department of Stem Cell Biology and Regenerative Medicine at USC; more than half of his lab members identify as members of the Hispanic community.

“The focus has to be on developing good scientists,” Almada says. “I learned from my past research mentors the importance of putting the needs of your students first and providing a supportive environment for everyone to excel, no matter where they start.”

As a mentor and researcher, Almada knows that no question and no challenge is off limits — foundations he built in Cambridge, where his graduate studies focused on teaching him to think, not just do.

“Digging deep into the science is what MIT taught me,” he says. “I’m now taking all of my knowledge in molecular biology and applying it to translationally oriented questions that I hope will benefit human health and longevity.”