netbet sports betting app

So-called “junk” DNA plays a key role in speciation
Eva Frederick | Whitehead Institute
August 23, 2021

More than 10 percent of our genome is made up of repetitive, seemingly nonsensical stretches of genetic material called satellite DNA that do not code for any proteins. In the past, some scientists have referred to this DNA as “genomic junk.”

Over a series of papers spanning several years, however, Whitehead Institute Member Yukiko Yamashita and colleagues have made the case that satellite DNA is not junk, but instead has an essential role in the cell: it works with cellular proteins to keep all of a cell’s individual chromosomes together in a single nucleus.

Now, in the latest installment of their work, published online July 24 in the journal Molecular Biology and Evolution, Yamashita and former postdoctoral fellow Madhav Jagannathan, currently an assistant professor at ETH Zurich, Switzerland, take these studies a step further, proposing that the system of chromosomal organization made possible by satellite DNA is one reason that organisms from different species cannot produce viable offspring.

“Seven or eight years ago when we decided we wanted to study satellite DNA, we had zero plans to study evolution,” said Yamashita, who is also a professor of biology at the Massachusetts Institute of Technology and an investigator with the Howard Hughes Medical Institute. “This is one very fun part of doing science: when you don’t have a preconceived idea, and you just follow the lead until you bump into something completely unexpected.”

NetBet live casino

Researchers have known for years that satellite DNA is highly variable between species. “If you look at the chimpanzee genome and the human genome, the protein coding regions are, like, 98 percent, 99 percent identical,” she says. “But the junk DNA part is very, very different.”

“These are about the most rapidly evolving sequences in the genome, but the prior perspective has been, ‘Well, these are junk sequences, who cares if your junk is different from mine?’” said Jagannathan.

But as they were investigating the importance of satellite DNA for fertility and survival in pure species, Yamashita and Jagannathan had their first hint that these repetitive sequences might play a role in speciation.

When the researchers deleted a protein called Prod that binds to a specific satellite DNA sequence in the fruit fly Drosophila melanogaster, the flies’ chromosomes scattered outside of the nucleus into tiny globs of cellular material called micronuclei, and the flies died. “But we realized at this point that this [piece of] satellite DNA that was bound by the Prod protein was completely missing in the nearest relatives of Drosophila melanogaster,” Jagannathan said. “It completely doesn’t exist. So that’s an interesting little problem.”

If that piece of satellite DNA was essential for survival in one species but missing from another, it could imply that the two species of flies had evolved different satellite DNA sequences for the same role over time.  And since satellite DNA played a role in keeping all the chromosomes together, Yamashita and Jagannathan wondered whether these evolved differences could be one reason different species are reproductively incompatible.

“After we realized the function [of satellite DNA in the cell], the fact that satellite DNA is quite different between species really hit like lightning,” Yamashita said. “All of a sudden, it became a completely different investigation.”

A tale of two fruit fly species

To study how satellite DNA differences might underlie reproductive incompatibility, the researchers decided to focus on two branches of the fruit fly family tree: the classic lab model Drosophila melanogaster, and its closest relative, Drosophila simulans. These two species diverged from each other two to three million years ago.

Researchers can breed a Drosophila melanogaster female to a Drosophila simulans male, “but [the cross] generates very unhappy offspring,” Yamashita said. “Either they’re sterile or they die.”

Yamashita and Jagannathan bred the flies together, then studied the tissues of the offspring to see what was leading these “unhappy” hybrids to drop like flies. Right away they noticed something interesting: “When we looked at those hybrid tissues, it was very clear that their phenotype was exactly the same as if you had disrupted the satellite DNA [-mediated chromosomal organization] of a pure species,” Yamashita said. “The chromosomes were scattered, and not encapsulated in a single nucleus.”

Furthermore, the researchers could create a healthy hybrid fly by mutating certain genes in the parent flies called “hybrid incompatibility genes,” which have been shown to localize to satellite DNA in the cells of pure species.  Via these experiments, the researchers were able to demonstrate how these genes affect chromosomal packaging in hybrids, and pinpoint the cellular phenotypes associated with them for the first time. “I think for me, that is probably the most critical part of this paper,” Jagannathan said.

Taken together, these findings suggest that because satellite DNA mutates relatively frequently, the proteins that bind the satellite DNA and keep chromosomes together must evolve to keep up, leading each species to develop their own “strategy” for working with the satellite DNA. When two organisms with different strategies interbreed, a clash occurs, leading the chromosomes to scatter outside of the nucleus.

In future studies, Yamashita and Jagannathan hope to put their model to the ultimate test: if they can design a protein that can bind the satellite DNA of two different species and hold the chromosomes together, they could theoretically ‘rescue’ a doomed hybrid, allowing it to survive and produce viable offspring.

This feat of bioengineering is likely years off. “Right now it’s just a pure conceptual thing,” Yamashita said. “In doing this tinkering, there’s probably a lot of specifics that will have to be solved.”

For now, the researchers plan to continue investigating the roles of satellite DNA in the cell, armed with their new knowledge of the part it plays in speciation. “To me, the surprising part of this paper is that our hypothesis was correct,” Jagannathan said. “I mean, in retrospect, there are so many ways things could have been inconsistent with what we hypothesized, so it’s kind of amazing that we’ve sort of been able to chart a clear path from start to finish.”

Company founded by MIT alumnus lets anyone run DNA experiments

MiniPCR bio has sold thousands of its inexpensive polymerase chain reaction machines to researchers and schools around the world.

Zach Winn | MIT News Office
August 20, 2021

If you gave students around the world the power to study and manipulate genes in a test tube, what would they do with it?

MiniPCR bio first began selling its portable, inexpensive polymerase chain reaction (PCR) machines in 2013. The machines allow users to multiply specific strands of DNA in minutes, following along with experiments through a phone app.

Since then, the founders have been amazed at the amount of learning and research that has come from the devices.

Researchers have taken the machines into the Amazon rainforest, the deep oceans, and onto remote islands to do things like classify the DNA of the Ebola virus, sequence genes in endangered animals, and monitor for disease. Hundreds of thousands of students have used the machines for hands-on classroom experiments. The machines have even gone to the International Space Station as part of miniPCR bio’s Genes in Space initiative.

The space experiments are designed by middle and high school students as one of miniPCR bio’s projects in education, its main focus. To date, miniPCR bio has sold more than 20,000 of its machines to schools in 80 countries across the globe.

“I still find it shocking,” miniPCR bio’s co-founder Ezequiel Alvarez Saavedra PhD ’08 says of the company’s impact. “We get emails from teachers every week thanking us and telling us how much learning improved in the classroom because of our machine. I never would have thought this would happen.”

Making PCR mainstream

Alvarez Saavedra conducted thousands of experiments with PCR machines, which help researchers replicate specific pieces of DNA and RNA, as part of his PhD work at MIT studying the C. elegans worm. After completing his PhD in 2008, he wasn’t sure how to continue his research career, but he’d worked at MIT’s Hobby Shop in his free time and knew he liked building things, so he began working with a small engineering firm to design a simpler machine.

“I wasn’t thinking of starting a company at all,” Alvarez Saavedra says. “I just liked engineering and I was hoping to learn more about it.”

PCR machines work through a series of temperature changes. First, DNA is heated up inside the machine’s sample tubes. The heat breaks the DNA’s two strands apart. Then, during a cool down phase, molecules specifying the start and end point of the DNA that scientists want to replicate latch onto their targets. As the PCR machine heats the sample back up, an netbet sports betting appenzyme fills in the target section of DNA, matching the A nucleotides with Ts and the C nucleotides with Gs. The heat-cool-heat cycle is repeated over and over until millions of copies of the target section have been generated.

“PCR is really the workhorse of molecular biology,” Alvarez Saavedra says. “PCR lets you zoom into your region of interest — the starting material could be an entire genome or a small piece of DNA — and then do something with it. You can sequence it, for example, or you could remove a piece of it.”

Traditional PCR machines cost thousands of dollars and typically use thermoelectric cooling to change temperatures. MiniPCR’s machines, the most popular of which costs $650, use a fan and a thin-film heater, simplifying their design and making their operation far less energy-intensive.

Those changes make the machines cheap. They’re also far easier to use than their lab-based counterparts. A simple app lets users select what kind of experiment they want to run, and a temperature graph with animated depictions lets students and researchers follow along at every stage.

In 2013, Alvarez Saavedra partnered with Sebastian Kraves, a fellow Argentinian who’d earned his PhD at Harvard Medical School, to consider the best use case for the new invention. The co-founders decided to try expanding access to PCR machines for middle and high school students around the globe.

To show educators the machines for the first time, the founders attended a professional development training session for teachers at MIT.

“We showed it for 10 minutes and a teacher at the back of the room immediately said, ‘I want 10 of those,’” Alvarez Saavedra remembers. “We though okay, there’s something here.”

The founders ended up building the first 20 machines themselves, storing growing numbers of them in Ezequiel’s living room and basement until his wife suggested they find an office.

Fortunately, miniPCR bio was quickly gaining traction in the education space. Many schools buy batches of miniPCR machines for groups of students to work with directly.

“U.S. schools have been teaching PCR for years, but pretty much no one at the time had PCR machines,” Alvarez Saavedra says. “If a school did have a PCR machine, it would sit at the back of the classroom. When you’re teaching you want small groups of students doing experiments that allows each one to be more hands-on.”

As miniPCR bio’s impact on education scaled, it also gained a loyal following among researchers who appreciate the device’s low price point, efficiency, and suitability to travel to remote regions.

Researchers have run the machines off batteries charged with solar panels and done experiments without leaving the field. When one researcher was trying to sequence the Ebola virus in a makeshift lab in Sierra Leone, the miniPCR machines he’d brought to train lab technicians proved more effective than the traditional — far more expensive — PCR machines he’d brought for his work.

“It’s very nice to get reminded what you’re doing has an impact,” Alvarez Saavedra says.

PCR and beyond

Early on, the founders had the idea for students to design experiments for astronauts to run in space. The idea grew into a national competition held in partnership with Boeing that invites middle and high school students to propose pioneering DNA experiments that address challenges in space exploration. Finalist teams receive miniPCR machines for their schools, and winners get to see their experiments carried out in the International Space Station.

“Kids find space and molecular biology very exciting,” Alvarez Saavedra says.

MiniPCR has done eight missions so far. The program is just one example of the miniPCR team’s ability to keep innovating. The company also offers inexpensive systems for visualizing DNA and enzymes. It’s also developed projects for running classroom experiments using gene editing and synthetic biology. The latter project, called Biobits, was codeveloped in the lab of Jim Collins, the Termeer Professor of Medical Engineering and Science at MIT.

Biobits gives students a hands-on introduction to synthetic biology by letting them create molecular factories that churn out brightly colored proteins, functional enzymes, and more. Ally Huang, a grad student in Collins’ lab who helped develop Biobits, joined the miniPCR team to help launch the first Biobits labs and has helped scale the program to classrooms across the country.

“We try to go where the exciting science is,” Alvarez Saavedra says. “With all these programs, it’s been crazy. You put it out and you start hearing from people in all these crazy places. In the beginning, this wasn’t even supposed to be a company. But it’s incredibly simple. I guess that’s the beauty of it.”

Jacqueline Lees and Rebecca Saxe named associate deans of science

Professors will help guide school-level initiatives and strategy.

Julia C. Keller | School of Science
August 16, 2021

Jaqueline Lees and Rebecca Saxe have been named associate deans serving in the MIT School of Science. Lees is the Virginia and D.K. Ludwig Professor for Cancer Research and is currently the associate director of the Koch Institute for Integrative Cancer Research, as well as an associate department head and professor in the Department of Biology at MIT. Saxe is the John W. Jarve (1978) Professor in Brain and Cognitive Sciences and the associate head of the Department of Brain and Cognitive Sciences (BCS); she is also an associate investigator in the McGovern Institute for Brain Research.

Lees and Saxe will both contribute to the school’s diversity, equity, inclusion, and justice (DEIJ) activities, as well as develop and implement mentoring and other career-development programs to support the community. From their home departments, Saxe and Lees bring years of DEIJ and mentorship experience to bear on the expansion of school-level initiatives.

Lees currently serves on the dean’s science council in her capacity as associate director of the Koch Institute. In this new role as associate dean for the School of Science, she will bring her broad administrative and programmatic experiences to bear on the next phase for DEIJ and mentoring activities.

Lees joined MIT in 1994 as a faculty member in MIT’s Koch Institute (then the Center for Cancer Research) and Department of Biology. Her research focuses on regulators that control cellular proliferation, terminal differentiation, and stemness — functions that are frequently deregulated in tumor cells. She dissects the role of these proteins in normal cell biology and development, and establish how their deregulation contributes to tumor development and metastasis.

Since 2000, she has served on the Department of Biology’s graduate program committee, and played a major role in expanding the diversity of the graduate student population. Lees also serves on DEIJ committees in her home department, as well as at the Koch Institute.

With co-chair with Boleslaw Wyslouch, director of the Laboratory for Nuclear Science, Lees led the ReseArch Scientist CAreer LadderS (RASCALS) committee tasked to evaluate career trajectories for research staff in the School of Science and make recommendations to recruit and retain talented staff, rewarding them for their contributions to the school’s research enterprise.

“Jackie is a powerhouse in translational research, demonstrating how fundamental work at the lab bench is critical for making progress at the patient bedside,” says Nergis Mavalvala, dean of the School of Science. “With Jackie’s dedicated and thoughtful partnership, we can continue to lead in basic research and develop the recruitment, retention, and mentoring and necessary to support our community.”

Saxe will join Lees in supporting and developing programming across the school that could also provide direction more broadly at the Institute.

“Rebecca is an outstanding researcher in social cognition and a dedicated educator — someone who wants our students not only to learn, but to thrive,” says Mavalvala. “I am grateful that Rebecca will join the dean’s leadership team and bring her mentorship and leadership skills to enhance the school.”

For example, in collaboration with former department head James DiCarlo, the BCS department has focused on faculty mentorship of graduate students; and, in collaboration with Professor Mark Bear, the department developed postdoc salary and benefit standards. Both initiatives have become models at MIT.

With colleague Laura Schulz, Saxe also served as co-chair of the Committee on Medical Leave and Hospitalizations (CMLH), which outlined ways to enhance MIT’s current leave and hospitalization procedures and policies for undergraduate and graduate students. Saxe was also awarded MIT’s Committed to Caring award for excellence in graduate student mentorship, as well as the School of Science’s award for excellence in undergraduate teaching.

In her research, Saxe studies human social cognition, using a combination of behavioral testing and brain imaging technologies. She is best known for her work on brain regions specialized for abstract concepts, such as “theory of mind” tasks that involve understanding the mental states of other people. Her TED Talk, “How we read each other’s minds” has been viewed more than 3 million times. She also studies the development of the human brain during early infancy.

She obtained her PhD from MIT and was a Harvard University junior fellow before joining the MIT faculty in 2006. In 2014, the National Academy of Sciences named her one of two recipients of the Troland Award for investigators age 40 or younger “to recognize unusual achievement and further empirical research in psychology regarding the relationships of consciousness and the physical world.” In 2020, Saxe was named a John Simon Guggenheim Foundation Fellow.

Saxe and Lees will also work closely with Kuheli Dutt, newly hired assistant dean for diversity, equity, and inclusion, and other members of the dean’s science council on school-level initiatives and strategy.

“I’m so grateful that Rebecca and Jackie have agreed to take on these new roles,” Mavalvala says. “And I’m super excited to work with these outstanding thought partners as we tackle the many puzzles that I come across as dean.”

Summer students thrive in Picower labs

Undergraduates from colleges across the country gain scientific training, mentorship and experience as participants in the MIT Summer Research Program

Picower Institute
August 11, 2021

A college student could imagine many ways to spend a summer, but for 11 undergraduates at universities from the Caribbean to California, an uncommon passion for science and an eagerness for immersion in current, world-class research made joining Picower Institute labs a compelling choice.

At a bustling poster session in early August where they presented their work, it was clear that the students hailing from underrepresented or disadvantaged backgrounds and non-research intensive home institutions, made the most of their participation in the MIT Summer Research Program (MSRP) in Biology and Brain and Cognitive Neuroscience. They said the experience, skills, contacts, and inspiration they gained can advance their academic ambitions.

netbet sports bettingPerforming experiments to study possible treatments for the developmental vision disorder amblyopia in the lab of Picower Professor Mark Bear gave Alysa Alejandro-Soto, a student at the University of Puerto Rico Mayaguez an inspiring exposure to fundamental lab neuroscience that can also have direct, future relevance to patients, she said.

“I really wanted to do neuroscience research but I hadn’t been able to do it in my undergraduate studies,” she said of her work alongside postdoctoral mentor Hector de Jesús-Cortés. “I want to do an MD/PhD and it’s really exciting for me to see how this could be applied clinically.”

Hanoka Belai said that her summer in the lab of Latham Family Associate Professor Myriam Heiman has recharged her interest in pursuing a neuroscience degree. A biotechnology major at Roxbury Community College, Belai said her research with postdoctoral mentor Brent Fitzwalter to advance a novel strategy for treating the terminal neurodegenerative condition Huntington’s disease was exciting because she wants to learn science to help people.

Heiman said she was delighted to host two MSRP students this summer. Along with Belai, she and graduate student Preston Ge also welcomed Rim Bozo who is on her way to Dartmouth College after graduating from Pioneer Charter School Of Science near Boston. Bozo said the chance to go from high school labs to working on studies of Parkinson’s disease at MIT provided exceptional preparation for college.

“They are both outstanding young scientists,” Heiman said. “The MSRP students are always very motivated and eager to learn so we always look forward to working with them.”

In all, eight Picower labs hosted at least one MSRP student.

Paola Alicea-Román from the University of Puerto Rico, Humacao, first worked with the Bear lab last summer, but could only do so virtually because of the Covid-19 pandemic. Even though her research applying a deep learning algorithm to assess the vision of mice with amblyopia was computational, she said, she reveled in the chance to be in the lab in person this year. Being there not only allowed her to help shape the experiments providing the data, it also gave opportunities to network with professors, fellow women in science and graduate students.

Relationships and mentorship are an especially important component of MSRP for many students who participate. Sonia Okekenwa, a student at Fisk University in Nashville, said a particularly valuable aspect of her work in the lab of Picower Professor Li-Huei Tsai was the frequent dialogue she had with postdoctoral mentor Vishnu Dileep and other lab members, who challenged her to think deeply about what she was finding out in her research mapping where DNA breaks open to enable neuronal processes (see p. 2).

Miriam Goras of Arizona State, who worked in the lab of William R. and Linda R. Young Professor Elly Nedivi with postdoc Baovi Vo, said she similarly valued the challenge of having to figure out genuine problems with no pre-determined answers. For instance, during her work this summer studying the molecular biology of treatment for bipolar disorder, she had to dig into the scientific literature to troubleshoot biochemical methods in the optimization of her cell culture experiment.

Several other Picower MSRP students, who included Jordina Pierre of the University of the Virgin Islands, Miguel Coste of Notre Dame, Joshua Powers of George Washington University, Patricia Pujols of Bayamon Central University, and Hanna Caris of Pomona College said they also valued the exposure, training, and guidance they gained through MSRP, which is coordinated by Director of Diversity and Science Outreach Mandana Sassanfar.

Powers, in fact, was back for his fourth summer after first engaging with MIT programs as a high schooler. His experience in the Flavell lab with postdoc Cassi Estrem has helped him clarify that he wants to pursue research as a career.

“The Flavell lab continues to show support for me, to teach me and go out of their way to make sure I’m keeping up with them for my benefit,” he said.

For Powers and his colleagues, these have been summers well spent.

New drug combo shows early potential for treating pancreatic cancer

Researchers find three immunotherapy drugs given together can eliminate pancreatic tumors in mice.

Anne Trafton | MIT News Office
August 5, 2021

Pancreatic cancer, which affects about 60,000 Americans every year, is one of the deadliest forms of cancer. After diagnosis, fewer than 10 percent of patients survive for five years.

While some chemotherapies are initially effective, pancreatic tumors often become resistant to them. The disease has also proven difficult to treat with newer approaches such as immunotherapy. However, a team of MIT researchers has now developed an immunotherapy strategy and shown that it can eliminate pancreatic tumors in mice.

The new therapy, which is a combination of three drugs that help boost the body’s own immune defenses against tumors, is expected to enter clinical trials later this year.

“We don’t have a lot of good options for treating pancreatic cancer. It’s a devastating disease clinically,” says William Freed-Pastor, a senior postdoc at MIT’s Koch Institute for Integrative Cancer Research. “If this approach led to durable responses in patients, it would make a big impact in at least a subset of patients’ lives, but we need to see how it will actually perform in trials.”

Freed-Pastor, who is also a medical oncologist at Dana-Farber Cancer Institute, is the lead author of the new study, which appears today in Cancer Cell. Tyler Jacks, the David H. Koch Professor of Biology and a member of the Koch Institute, is the paper’s senior author.

Immune attack

The body’s immune system contains T cells that can recognize and destroy cells that express cancerous proteins, but most tumors create a highly immunosuppressive environment that disables these T cells, helping the tumor to survive.

Immune checkpoint therapy (the most common form of immunotherapy currently being used clinically) works by removing the brakes on these T cells, rejuvenating them so they can destroy tumors. One class of immunotherapy drug that has shown success in treating many types of cancer targets the interactions between PD-L1, a cancer-linked protein that turns off T cells, and PD-1, the T cell protein that PD-L1 binds to. Drugs that block PD-L1 or PD-1, also called checkpoint inhibitors, have been approved to treat cancers such as melanoma and lung cancer, but they have very little effect on pancreatic tumors.

Some researchers had hypothesized that this failure could be due to the possibility that pancreatic tumors don’t express as many cancerous proteins, known as neoantigens. This would give T cells fewer targets to attack, so that even when T cells were stimulated by checkpoint inhibitors, they wouldn’t be able to identify and destroy tumor cells.

However, some recent studies had shown, and the new MIT study confirmed, that many pancreatic tumors do in fact express cancer-specific neoantigens. This finding led the researchers to suspect that perhaps a different type of brake, other than the PD-1/PD-L1 system, was disabling T cells in pancreatic cancer patients.

In a study using mouse models of pancreatic cancer, the researchers found that in fact, PD-L1 is not highly expressed on pancreatic cancer cells. Instead, most pancreatic cancer cells express a protein called CD155, which activates a receptor on T cells known as TIGIT.

When TIGIT is activated, the T cells enter a state known as “T cell exhaustion,” in which they are unable to mount an attack on pancreatic tumor cells. In an analysis of tumors removed from pancreatic cancer patients, the researchers observed TIGIT expression and T cell exhaustion from about 60 percent of patients, and they also found high levels of CD155 on tumor cells from patients.

“The CD155/TIGIT axis functions in a very similar way to the more established PD-L1/PD-1 axis. TIGIT is expressed on T cells and serves as a brake to those T cells,” Freed-Pastor says. “When a TIGIT-positive T cell encounters any cell expressing high levels of CD155, it can essentially shut that T cell down.”

Drug combination

The researchers then set out to see if they could use this knowledge to rejuvenate exhausted T cells and stimulate them to attack pancreatic tumor cells. They tested a variety of combinations of experimental drugs that inhibit PD-1 and TIGIT, along with another type of drug called a CD40 agonist antibody.

CD40 agonist antibodies, some of which are currently being clinically evaluated to treat pancreatic cancer, are drugs that activate T cells and drive them into tumors. In tests in mice, the MIT team found that drugs against PD-1 had little effect on their own, as has previously been shown for pancreatic cancer. They also found that a CD40 agonist antibody combined with either a PD-1 inhibitor or a TIGIT inhibitor was able to halt tumor growth in some animals, but did not substantially shrink tumors.

However, when they combined CD40 agonist antibodies with both a PD-1 inhibitor and a TIGIT inhibitor, they found a dramatic effect. Pancreatic tumors shrank in about half of the animals given this treatment, and in 25 percent of the mice, the tumors disappeared completely. Furthermore, the tumors did not regrow after the treatment was stopped. “We were obviously quite excited about that,” Freed-Pastor says.

Working with the Lustgarten Foundation for Pancreatic Cancer Research, which helped to fund this study, the MIT team sought out two pharmaceutical companies who between them have a PD-1 inhibitor, TIGIT inhibitor, and CD40 agonist antibody in development. None of these drugs are FDA-approved yet, but they have each reached phase 2 clinical trials. A clinical trial on the triple combination is expected to begin later this year.

“This work uses highly sophisticated, genetically engineered mouse models to investigate the details of immune suppression in pancreas cancer, and the results have pointed to potential new therapies for this devastating disease,” Jacks says. “We are pushing as quickly as possible to test these therapies in patients and are grateful for the Lustgarten Foundation and Stand Up to Cancer for their help in supporting the research.”

Alongside the clinical trial, the MIT team plans to analyze which types of pancreatic tumors might respond best to this drug combination. They are also doing further animal studies to see if they can boost the treatment’s effectiveness beyond the 50 percent that they saw in this study.

In addition to the Lustgarten Foundation, the research was funded by Stand Up To Cancer, the Howard Hughes Medical Institute, Dana-Farber/Harvard Cancer Center, the Damon Runyon Cancer Research Foundation, and the National Institutes of Health.

Unusual Labmates: Fruit flies
Greta Friar | Whitehead Institute
August 4, 2021

All the buzz in the lab

On a sunny summer morning in Cambridge, Massachusetts, Mariyah Saiduddin walked into a room and was met by the sight of thousands of fruit flies. For most people, this would be an emergency: time to call an exterminator, take out the trash, and scrub the room from top NetBet sportto bottom. However, this room full of flies is part of Whitehead Institute Director Ruth Lehmann’s lab, where fruit flies are seen not as pests but as valuable research tools—and are safely contained in vials. Saiduddin is a graduate student researcher in Lehmann’s lab who uses a fraction of the flies in the room in her research.

The flies found in Lehmann’s lab, and in the adjacent lab run by Whitehead Institute Member Yukiko Yamashita, are not exactly like their less-beloved wild counterparts. Fruit flies have been used in research for more than a century, and in that time, they have been engineered to become powerful, malleable models capable of answering questions in many areas of research. The most common species used in research is Drosophila melanogaster, often referred to simply as “Drosophila.” The researchers who use flies call themselves Drosophilists, and their community around the world works together to maintain a rich variety of flies and create new tools with which to manipulate those flies. In the past century, work in fruit flies has led to six Nobel Prizes in Physiology or Medicine, and has shed light on topics from the basics of genetics, to the principles of embryonic development, to circadian rhythms, to the immune system, to a plethora of diseases.

A very fly model organism

Fruit flies became a go-to research tool during the explosion of genetics research around the turn of the 20th century. What makes them such a good model organism? First of all, they are easy and relatively cheap to raise in large numbers. They have short lifespans and quick reproduction times, so researchers can rapidly breed and study multiple generations. Fruit flies are ready to reproduce—growing from embryo to larva to adult—in under two weeks and then can lay hundreds of eggs in a matter of days.

Fruit flies and humans have enough similarities in their genetics and development that research in fruit flies often reflects human biology. In particular, when it comes to genetics, fruit flies have more commonalities with humans than they have differences. Nearly three-quarters of the genes that cause diseases in humans have an equivalent gene—one derived from the same ancestral gene—in fruit flies.
Not only are fruit flies naturally suited for research, but over the years they have been engineered to become even better research subjects. One of the earliest improvements to fruit flies as a research model came from researchers discovering that they could create flies with genetic mutations that change things like a fly’s eye color, wing shape, body shape, or the bristles on its thorax. Researchers began selectively breeding different lines of fruit flies to have these distinctive physical traits or “markers,” which make them easy to tell apart.
Researchers can tie a visible genetic marker, such as curly wings, to a genetic mutation that they are studying that may not be visible, so that they can easily sort their flies. For example, Whitehead Institute researchers using flies to study mutations that affect the germ cells, the set of cells that make or become eggs and sperm, cannot tell just by looking at a fly whether it has a mutation that affects germ cells, but if they tie inheritance of the mutation to the curly wing marker, then the flies with the desired mutation become easy to identify.
Drosophila biologists have adapted tools from other model organisms to control and study essentially any gene in flies. The Gal4-UAS system, which was developed based on a gene and gene regulator found in yeast, is now commonly used in flies. The system lets researchers activate a gene only in certain tissues or sets of cells. For example, researchers may want to know what part of the brain a certain gene is active in, so they will use the Gal4-UAS system to express green fluorescent protein (GFP) only in cells that would also normally express the gene of interest, allowing researchers to map gene activity based on fluorescence. Or, Gal4-UAS can be used to turn off a gene involved in embryonic development, to see what changes when that gene is not active. This is a common approach that researchers use to figure out a gene’s function; it works in the same way that one could deduce the purpose of brakes on a car by taking the brakes off and observing the car being unable to stop when its driver steps on the brake pedal. Gal4 lines can be developed and tested quickly, in a couple of months, and because the Drosophilist community tends to share their resources, as soon as one lab has developed a Gal4 line for a gene, any fruit fly lab can use that tool to ask their own research questions. Thousands of Gal4 lines are maintained in centralized collections, making them very easy to access.

The embryonic days of fly research

The transformation of fruit flies from wild pests into top notch research tools began in the early 1900s. Charles W. Woodworth, at Harvard University at the turn of the 20th century, is credited with being the first researcher to breed Drosophila in large numbers and with suggesting that the species could be used to study genetics, then a new field of research.[2] Thomas Hunt Morgan, at Columbia University, was one of several researchers to follow Woodworth in using fruit flies for his research, and it was Morgan who really established fruit flies as a model organism, through both his own success and that of the students who came out of his lab and the soon-famous Columbia fly room.

For his research, Morgan bred fruit flies until one developed a mutation, white eyes (most fruit flies’ eyes are red), and then continued breeding the mutant and its descendants to track patterns in inheritance of the white-eyes trait. With these experiments, Morgan showed that genes, which had recently been established as the smallest units of inheritance, are organized on chromosomes, cellular structures each one of which contains a certain, consistent set of genes. One of Morgan’s students, Alfred Sturtevant, expanded on this work, showing that the genes on each chromosome can be mapped in a specific linear order. The proof of the chromosome theory of inheritance won Morgan the 1933 Nobel Prize in Physiology or Medicine and the mutation that Morgan identified, white, is still used as a marker in fruit flies today. Morgan and the scientists who came through his lab continued to do groundbreaking research, demonstrating the potency of fruit flies as a model, and soon flies became a popular research tool.

Research in fruit flies has led to five further Nobel Prizes since Morgan’s, including the 1995 prize awarded to Edward B. Lewis, Christiane Nüsslein-Volhard and Eric Wieschaus for their discoveries regarding “the genetic control of early embryonic development.” These three researchers identified and discovered the function of key genes involved in determining and carrying out the blueprint for a fly’s body during development. Nüsslein-Volhard and Wieschaus systematically mutated many flies in order to discover the genes involved in body patterning. After they introduced lots of mutations, they observed what happened to the flies, and then they determined which genes had been mutated to cause the effects to body patterning that they observed. Using this strategy, they identified and characterized many key genes involved in guiding the development of an embryo into a segmented body.

Lewis, meanwhile, identified and determined the function of what would come to be known as homeotic genes, the genes that determine which specific body parts grow in each body segment: these genes essentially determine the blueprint for the fly’s body, and—as Lewis showed—when mutated lead to some very unusual body plans. Collectively, these researchers’ discoveries illuminated both the genetics and the evolution of the body plan in flies—work that was quickly extrapolated to other species, including humans, whose development occurs in a similar fashion.

Lewis, Nüsslein-Volhard and Wieschaus’ work set the stage for future researchers such as Lehmann and Yamashita who study development in flies. In fact, Nüsslein-Volhard had a direct influence on Lehmann: Lehmann trained with her as a graduate student. Nüsslein-Volhard’s later work provided important insights into the morphogen gradients that help guide the developing embryo in assembling itself correctly, and included an in-depth gene screen of zebrafish using the same extensive process of mutation and observation that she and Wieschaus had used in Drosophila.

Researchers at Whitehead Institute are using fruit flies to answer a wide variety of questions. In previous years, former Whitehead Institute Member Terry Orr-Weaver used Drosophila to study the process of cell division during development. She looked at questions such as what determines cell size, what regulates the transition from egg to embryo, and how DNA is accurately replicated and sorted into dividing cells. Whitehead Institute Member David Bartel, also a professor of biology at the Massachusetts Institute of Technology (MIT) and an HHMI investigator, studies RNA and has done some of that research in flies. His work has improved our understanding of how tiny regulatory RNAs called microRNAs target and initiate the destruction of the RNAs that code for proteins in many species, including flies. He used these insights to create TargetScanFly, a database that provides researchers around the world with fly microRNAs’ predicted targets. Bartel’s lab also recently discovered how some microRNAs are rapidly degraded in Drosophila cells and how other types of small regulatory RNAs are protected from this degradation. In other studies of gene regulation in flies, performed in collaboration with Orr-Weaver, the Bartel lab identified the RNAs that are first produced by the developing embryo and determined why RNAs of some genes are much better than those of others at producing proteins in fly oocytes and early embryos.

Lehmann and Yamashita use fruit flies to study germ cells, the cells set aside to make or become eggs and sperm—as did Orr-Weaver. The germ line is set aside from the rest of the body’s cells early on, and has the rare property of being, essentially, immortal: all of the other cell lines in the body will eventually die with it, but germ cells survive to become offspring, which contain new germ cells, and so on through the generations.

Rewiring cell division to make eggs and sperm
Whitehead Institute
July 30, 2021

To create eggs and sperm, cells must rewire the process of cell division. Mitosis, the common type of cell division that our bodies use to grow everything from organs to fingernails and to replace aging cells, produces two daughter cells with the same number of chromosomes and approximately the same DNA sequence as the original cell. Meiosis, the specialized cell division that makes egg and sperm in two rounds of cell division, creates four granddaughter cells with new variations in their DNA sequence and half as many chromosomes in each cell. Meiosis uses most of the same cellular machinery as mitosis to achieve this very different outcome; only a few key molecular players prompt the rewiring from one type of division to another. One such key player is the protein Meikin, which is found exclusively in cells undergoing meiosis.

New research from Whitehead Institute Member Iain Cheeseman, graduate student Nolan Maier and collaborators Professor Michael Lampson and senior research scientist Jun Ma at the University of Pennsylvania demonstrates how Meikin is elegantly controlled, and sheds light on how the protein acts to serve multiple roles over different stages of meiosis. The findings, which appear in Developmental Cell on July 30, reveal that Meikin is precisely cut in half midway through meiosis. Instead of this destroying the protein, one half of the molecule, known as C-Meikin, goes on to play a critical role as a previously hidden protein actor in meiosis.

“Cells have this fundamental process, mitosis, during which they have to divide chromosomes evenly or it will cause serious problems like cancer, so the system has to be very robust,” Maier says. “What’s incredible is that you can add one or two unique meiotic proteins like Meikin and dramatically change the whole system very quickly.”

Helping chromosomes stick together

During both mitosis and meiosis, sister chromatids — copies of the same chromosome — pair up to form the familiar “X” shape that we recognize as a chromosome. In mitosis, each chromatid—each half of the X — is connected to a sort of cellular fishing line and these lines reel the chromatids to opposite ends of the cell, where the two new cells are formed around them. However, in the first round of division in meiosis, the sister chromatids stick together, and one whole “X” is reeled into each new cell. Meikin helps to achieve this different outcome by ensuring that, while the chromosomes are being unstuck from each other in preparation for being pulled apart, each pair of sister chromatids stays glued together in the right place. Meikin also helps ensure that certain cellular machinery on the sister chromatids is fused so that they will connect to the same line and be reeled together to the same side of the cell.

More specifically, when chromosomes are first paired up, they are glued together by adhesive molecules in three regions: the centromere, or center of the X, where Meikin localizes; the region around the center; and the arms of the X. In the first round of meiosis, Meikin helps to keep the glue in the region around the center intact, so the sister chromatids will stick together. Simultaneously, Meikin helps to prime the center region to be unglued, while a separate process unglues the arms. This ungluing allows the chromosomes to separate and be prepared for later stages of meiosis.

netbet sports betting appCheeseman and Maier initially predicted that Meikin’s role ended after meiosis I, the first round of meiotic cell division. In meiosis II, the second round of cell division, the cells being created should end up with only one sister chromatid each, and so the chromatids must not be kept glued together. Maier found that near the end of meiosis I, Meikin is cleaved in two by an enzyme called Separase, the same molecule that cleaves the adhesive molecules gluing together the chromosomes. At first, this cleavage seemed like the end of Meikin and the end of this story.
A hidden role for a hidden proteinHowever, unexpectedly, the researchers found that cells lacking Meikin during the second half of meiosis do not divide properly, prompting them to take another look at what happens to Meikin after it gets cleaved. They found that Separase cleaves Meikin at a specific point — carving it with the precision of a surgeon’s scalpel — to create C-Meikin, a previously unknown protein that turns out to be necessary for meiosis II. C-Meikin has many of the same properties as the intact Meikin molecule, but it is just different enough to take on a different role: helping to make sure that the chromosomes align properly before their final division.

“There’s a lot of protein diversity in cells that you would never see if you don’t go looking for it, if you only look at the DNA or RNA. In this case, Separase is creating a completely different protein variant of Meikin than can function differently in meiosis II,” says Cheeseman, who is also a professor of biology at Massachusetts Institute of Technology. “I’m very excited to see what we might discover about other hidden protein forms in cell division.”

Recombining ideas

Answering the question of Meikin’s role and regulation throughout meiosis required a close collaboration and partnership between Maier and Lampson lab researcher Ma – the Lampson lab being experts on studying meiosis using mouse models. Working with mouse oocytes (immature egg cells), Ma was able to reveal the behaviors and critical contributions of Meikin cleavage in meiotic cells in mice. Both labs credit the close exchange with helping them to get a deeper understanding of how cells rewire for meiosis.

“It was a pleasure working together to understand how some of the specialized meiotic functions that are necessary for making healthy eggs and sperm are controlled,” Lampson says.

Finally, once cells have completed these specialized meiotic divisions, the researchers found that it was critical for oocytes to fully eliminate Meikin. The researchers determined that, after meiosis two, C-Meikin is degraded by another molecule (the anaphase-promoting complex or APC/C)—this time for good. With Meikin gone and the rewiring of cell division reversed, eggs and sperm are ready for mitosis; should they fuse and form an embryo, that is the next cell division they will undergo. The researchers note that the way Meikin is regulated by being broken down — first into C-Meikin and then completely — may help cells to organize their timing during meiosis. Breaking apart a protein is an irreversible step that creates a clear demarcation between before and after in a multi-step process.The researchers hope that by uncovering the intricacies of meiosis, they may shed light on what happens when the creation of eggs and sperm goes wrong, and so perhaps contribute to our understanding of infertility. Cheeseman also hopes that by studying how mitotic processes are rewired for meiosis, his lab can gain new insights into the original wiring of mitosis.

Mapping the cellular circuits behind spitting

Roundworms change the flow of material in and out of their mouths in response to bright light, revealing a new way for neurons to control muscle cells.

Raleigh McElvery
July 23, 2021

For over a decade, researchers have known that the roundworm Caenorhabditis elegans can detect and avoid short-wavelength light, despite lacking eyes and the light-absorbing molecules required for sight. As a graduate student in the Horvitz lab, Nikhil Bhatla proposed an explanation for this ability. He observed that light exposure not only made the worms wriggle away, but it also prompted them to stop eating. This clue led him to a series of studies that suggested that his squirming subjects weren’t seeing the light at all — they were detecting the noxious chemicals it produced, such as hydrogen peroxide. Soon after, the Horvitz lab realized that worms not only taste the nasty chemicals light generates, they also spit them out.

Now, in a study recently published in eLife, a team led by former graduate student Steve Sando reports the mechanism that underlies spitting in C. elegans. Individual muscle cells are generally regarded as the smallest units that neurons can independently control, but the researchers’ findings question this assumption. In the case of spitting, they determined that neurons can direct specialized subregions of a single muscle cell to generate multiple motions — expanding our understanding of how neurons control muscle cells to shape behavior.

“Steve made the remarkable discovery that the contraction of a small region of a particular muscle cell can be uncoupled from the contraction of the rest of the same cell,” says H. Robert Horvitz, the David H. Koch Professor of Biology at MIT, a member of the McGovern Institute for Brain Research and the Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute Investigator, and senior author of the study. “Furthermore, Steve found that such subcellular muscle compartments can be controlled by neurons to dramatically alter behavior.”

A roundworm spits after it is exposed to the nasty-tasting hydrogen peroxide produced by bright light. Video by Steve Sando.

Roundworms are like vacuum cleaners that wiggle around hoovering up bacteria. The worm’s mouth, also known as the pharynx, is a muscular tube that traps the food, chews it, and then transfers it to the intestines through a series of “pumping” contractions.

Researchers have known for over a decade that worms flee from UV, violet, or blue light. But Bhatla discovered that this light also interrupts the constant pumping of the pharynx, because the taste produced by the light is so nasty that the worms pause feeding. As he looked closer, Bhatla noticed the worms’ response was actually quite nuanced. After an initial pause, the pharynx briefly starts pumping again in short bursts before fully stopping — almost like the worm was chewing for a bit even after tasting the unsavory light. Sometimes, a bubble would escape from the mouth, like a burp.

After he joined the project, Sando discovered that the worms were neither burping nor continuing to munch. Instead, the “burst pumps” were driving material in the opposite direction, out of the mouth into the local environment, rather than further back into the pharynx and intestine. In other words, the bad-tasting light caused worms to spit. Sando then spent years chasing his subjects around the microscope with a bright light and recording their actions in slow motion, in order to pinpoint the neural circuitry and muscle motions required for this behavior.

“The discovery that the worms were spitting was quite surprising to us, because the mouth seemed to be moving just like it does when it’s chewing,” Sando says. “It turns out that you really needed to zoom in and slow things down to see what’s going on, because the animals are so small and the behavior is happening so quickly.”

To analyze what’s happening in the pharynx to produce this spitting motion, the researchers used a tiny laser beam to surgically remove individual nerve and muscle cells from the mouth and discern how that affected the worm’s behavior. They also monitored the activity of the cells in the mouth by tagging them with specially-engineered fluorescent “reporter” proteins.

They saw that while the worm is eating, three muscle cells towards the front of the pharynx called pm3s contract and relax together in synchronous pulses. But as soon as the worm tastes light, the subregions of these individual cells closest to the front of the mouth become locked in a state of contraction, opening the front of the mouth and allowing material to be propelled out. This reverses the direction of the flow of the ingested material and converts feeding into spitting.

The team determined that this “uncoupling” phenomenon is controlled by a single neuron at the back of the worm’s mouth. Called M1, this nerve cell spurs a localized influx of calcium at the front end of the pm3 muscle likely responsible for triggering the subcellular contractions.

M1 relays important information like a switchboard. It receives incoming signals from many different neurons, and transmits that information to the muscles involved in spitting. Sando and his team suspect that the strength of the incoming signal can tune the worm’s behavior in response to tasting light. For instance, their findings suggest that a revolting taste elicits a vigorous rinsing of the mouth, while a mildly unpleasant sensation causes the worm spit more gently, just enough to eject the contents.

In the future, Sando thinks the worm could be used as a model to study how neurons trigger subregions of muscle cells to constrict and shape behavior — a phenomenon they suspect occurs in other animals, possibly including humans.

“We’ve essentially found a new way for a neuron to move a muscle,” Sando says. “Neurons orchestrate the motions of muscles, and this could be a new tool that allows them to exert a sophisticated kind of control. That’s pretty exciting.”

Former Horvitz lab graduate student Steve Sando studies the neurons that allow roundworms to taste the chemicals produced by light — and then spit them out.

Citation:
“An hourglass circuit motif transforms a motor program via subcellularly localized muscle calcium signaling and contraction”
eLife, online July 2, 2021, DOI: 10.7554/eLife.59341
Steven R Sando, Nikhil Bhatla, Eugene L Q Lee, and H. Robert Horvitz

Probing pathogen spread during a global pandemic

Bailey Bowcutt investigated COVID-19 cases in rural Wyoming before coming to MIT for the summer and applying her knowledge to a new cellular invader.

Raleigh McElvery
July 23, 2021

The first time Bailey Bowcutt saw a lab it was nothing like she expected. Rather than a stark, sterile setting with sullen figures floating around like ghosts in white lab coats, the atmosphere was cordial and the dress casual. Some scientists even sported vibrant shirts with Marvel characters. A high school senior on a class field trip, Bowcutt couldn’t have predicted that the next time she’d set foot in the Wyoming Public Health Laboratory she’d no longer be a visitor, but a researcher performing diagnostic testing during a global pandemic. Now, as COVID-19 restrictions begin to lift, she’s taking the research tools she’s learned to Cambridge, Massachusetts to complete the Bernard S. and Sophie G. Gould MIT Summer Research Program in Biology (BSG-MSRP-Bio) and investigate how other types of pathogens spread.

Growing up in rural Wyoming, netbet sports betting appBowcutt had little exposure to science because there were few research institutes close by. But watching family members suffer from gastrointestinal illness and other infections spurred her to pursue a degree in microbiology at Michigan State University (MSU). Shortly after she arrived on campus in the fall of 2019, she joined Shannon Manning’s lab studying antibiotic resistance in cattle.

Cows are prone to contracting a bacterial infection of the udder called mastitis. (In humans, a similar inflammation can occur in breast tissue.) Manning’s lab is looking at how antibiotic treatments affect the bovine gut microbiome and emergence of antibiotic resistance genes. Bowcutt’s role was to help identify these super bugs inside the cows’ gastrointestinal tracts.

“I got to go to the farm to take samples, which involved a glove that goes all the way up to the shoulder and some invasive maneuvers inside cows,” she explains. “Luckily, I was just the bag holder!”

Intimate sample collection aside, Bowcutt was excited about the work because it combined agriculture and human health research to solve issues plaguing rural communities. But her time on the farm was cut short when COVID-19 cases climbed in early 2020. She headed back to her home in Wyoming to begin remote MSU classes and, reminiscing about her field trip to the Wyoming Public Health Laboratory, reached out to the director to see if there were any internship opportunities.

“I’d barely learned how to do science at that point, but they needed people who could handle a pipette, so they took me,” she says. “I ended up being one of the first people there helping with COVID research, and I stayed for about a year-and-a-half while I took online classes.”

The lab would receive nasopharyngeal swabs from COVID-19 patients, and Bowcutt’s first task was to help extract RNA from the samples. Later, she transitioned to another project, which required performing PCR on untreated wastewater samples to glean a population-level understanding of where COVID-19 outbreaks were occurring.

She began toying with the idea of pursuing a PhD, but wasn’t sure what it would entail. So, in early 2021, she started Googling summer science programs and stumbled on BSG-MSRP-Bio. She was accepted, and paired with one of the very labs that had caught her eye online: assistant professor Becky Lamason’s group.

Microscopy image of parasites rocketing around inside cells
Listeria monocytogenes (yellow) rocket around their host cells (outlined in cyan) before ramming through the host’s membrane and that of its neighbor, forming a protrusion that is engulfed by the recipient cell. Image by Cassandra Vondrak.

“If you’ve ever seen microscopy pictures from the Lamason lab, they’re just so beautiful,” Bowcutt explains. Beautiful, yes — but she would soon learn these snapshots capture a chilling cellular invasion and molecular heist.

The Lamason lab watches malicious bacteria as they hijack molecules in human host cells to build long tails, rocket around, and punch through the cell membrane to spread. Bowcutt’s mentor, graduate student Yamilex Acevedo-Sánchez, focuses on the food-borne bacterium Listeria monocytogenes, which targets the gastrointestinal tract. Acevedo-Sánchez’s research aims to understand the host cell pathways that Listeria commandeers to move from one cell to the next in a process called cell-to-cell spread.

Together, Acevedo-Sánchez and Bowcutt are investigating several proteins in the human host cell involved in cellular transport and membrane remodeling (Caveolin-1, Pacsin2, and Fes), which could regulate Listeria’s spread. Over the summer, the duo has been adjusting the levels of these proteins and observing what happens to Listeria’s ability to move from cell-to-cell.

Bowcutt spends most of her days doing Western blots; growing Listeria and mammalian cells; and combining immunofluorescence assays with fixed and live cell microscopy to take her own striking microscopy images and movies of the parasites.

“I expected the work environment at MIT to be very intense, but everyone has been really friendly and willing to answer questions,” she says. “Some of my favorite experiences have just been in the lab while everyone is bustling around. It’s a welcome change after so much COVID-19 isolation.”

Now that the COVID-era occupancy restrictions have lifted, Bowcutt’s lab bench neighbor is Lamason herself. “She’s next to me doing experiments all the time,” Bowcutt explains, “which is cool because she’s really engaging with the research in the same way we are.”

Bowcutt says her summer experience has given her some much-needed practice designing research questions and devising the experiments to answer them. She’s also acquired a new skill she didn’t anticipate: interpreting ambiguous results and developing follow-up experiments to clarify them.

These days, the prospect of a PhD seems much less intimidating. In fact, the Lamason lab has done more than simply pique Bowcutt’s interested in fundamental biology research. She’s now considering ways to combine her microbiology skills with her interest in rural health care.

“I didn’t expect to see this much growth in myself,” she says, “and I know it’s making me a better scientist. I’m excited to return to MSU in the fall because I feel like I can do so much more now — and I would totally do it again.”

Lodish receives lifetime achievement award
Merrill Meadow | Whitehead Institute
July 13, 2021

The American Society of Hematology (ASH), will honor Whitehead Institute Founding Member Harvey Lodish with its Wallace H. Coulter Award for Lifetime Achievement in Hematology.

The Coulter Award—ASH’s highest honor—recognizes an individual who has demonstrated a lasting commitment to the field of hematology through outstanding contributions to education, research, and practice.

Lodish is being honored for his six decades of key contributions to hematology, including his studies of the structure and biogenesis of red blood cells and his use of those cells as vehicles for delivering therapeutics. His research has provided important insights into several red cell diseases, including beta thalassemia and polycythemia vera; and he identified a new family of growth factor receptors, now known as the cytokine receptor superfamily. Lodish is also being recognized for his mentorship of more than 200 students and fellows, including two Nobel Prize recipients.

He will formally receive the Award at the 2021 ASH Annual Meeting in December.