Biology

Leslie Leinwand & The Science of Getting Things Done

Anonymous — Tue, 16 Jul 2024 06:00:00 +0000

Leslie Leinwand & The Science of Getting Things Done Anonymous (not verified) Tue, 07/16/2024 - 00:00

Lisa Marshall

Some might say the cards were stacked against Leslie Leinwand.

At age five, the precocious kindergartner was plucked from her Manhattan home and transplanted to the one-stoplight town of York, South Carolina, after the sudden death of her father, an internal medicine doctor. Her mother remarried a man who told young Leinwand repeatedly that, “girls didn’t need to go to college.” Then, when she was 13, tragedy took her mother and she was sent to live with extended family.

Leinwand persisted, landing at a small college in North Carolina where an astute professor noticed her interest in science and insisted she take a summer organic chemistry course at Cornell University.

“That’s when my somewhat sad story changed,” she recalls, now seated in her spacious office at the glistening, $210-million biotech facility she helped bring to life. “All because I had this fantastic professor.”

Today, Leinwand is a distinguished professor of molecular, cellular and developmental biology and the chief scientific officer of the BioFrontiers Institute at ŷ��ڱ��Ƶ Boulder. She has achieved what many scientists only dream about: turning a seed of scientific inquiry into a multibillion-dollar company that saves lives — more than once.

Leinwand stayed at Cornell and helped pay her way through by working as a fraternity house waitress. She later earned her PhD in genetics from Yale and served on the faculty at Albert Einstein College of Medicine for 15 years before landing in Boulder in 1995.

Throughout this time, one fundamental question drove her research: What genes and proteins are responsible for making the heart function properly, and what causes this complex machine to break down in some people?

“She is very special. When she discovers things in her lab, she doesn’t stop there,” said Nobel laureate and Distinguished Professor of Biochemistry Tom Cech, who has known Leinwand for three decades. “She works tirelessly, doing whatever it takes, to make something happen that will impact patients.”

Healing a big, sick heart

Much of Leinwand’s work has centered on hypertrophic cardiomyopathy (HCM), which she describes simply as a “big, sick heart.”

It is the most common genetic heart disease in the United States, impacting roughly one in 500 people, as well as the most common cause of sudden death among athletes — who often don’t know they have it and push their hearts too hard, with lethal results.

HCM first made headlines in 1990 when Hank Gathers, an all-American college basketball star, collapsed and died while on the court during a game at the age of 23. Since then, a long list has followed, including Reggie Lewis of the Boston Celtics, who died on a basketball court shortly after Gathers in 1993.

In patients with HCM, their hearts — the walls thickened by disease — squeeze too hard and don’t fully relax, which burns through energy, leaves them breathless, causes the heart to race and depletes their energy.

HCM gets worse over time — and, until recently, there was no medication to treat it.

Leinwand’s interest in the disease dates back to 1985, when she first began studying a protein called myosin, which converts chemical energy into mechanical energy to move muscles, including the heart. Early on, she suspected that glitches in this ubiquitous protein might contribute to heart troubles and that studying them could ultimately lead to new therapies.

“It was an idea before its time,” she recalls. “We didn’t have the technology back then that we did later.”

First, she and her students had to develop a way to manufacture myosin in the lab so they could study it. That alone took years.

In 1996, Leinwand and other ŷ��ڱ��Ƶ colleagues took what they had learned about myosin and founded Myogen, a startup that developed two novel drugs for treating hypertension, which sold to pharma giant Gilead Sciences for $2.6 billion in 2006.

Ultimately, Leinwand’s team determined that faulty myosin was a key culprit in HCM.

In 2012, she joined Harvard’s Christine and Jonathan Seidman, who study the genetic mechanisms of heart disease, and Stanford biochemist James Spudich, who studies how muscles contract, to create the biomedical company MyoKardia.

MyoKardia developed a drug that attaches to the faulty protein, effectively cranking down the heart’s overactive motor. The drug was tested in clinical trials and mavacamten (brand name Camzyos) was born.

Bristol Myers Squibb bought MyoKardia for $13 billion in 2020 and, in April of 2022, the Food and Drug Administration approved mavacamten as the first and only cardiac myosin inhibitor approved in the United States for treating HCM.

“We had hoped that the best outcome could be that the disease progression was slowed, but what cardiologists are telling us is that they are actually seeing a reversal in some patients,” says Leinwand.

Leinwand is not one to get emotional in public. But she can’t help but choke up a bit when asked how this makes her feel.

“It has been the most amazing thing to hear patients say things like, ‘I can now walk up a flight of steps again. I am no longer bedridden. I can get out of my house.’ It feels great.”

Paying it forward

Leinwand has no plans to retire anytime soon. The BioFrontiers Institute, which she and her colleagues dreamed up in the early 2000s, is now a thriving intellectual melting pot, bringing hundreds of physicists, engineers, biologists, chemists, geneticists and computer scientists from around the world together under one roof to improve human health.

Today, her Python Project, another way-outside-the-box idea she came up with in 2006, persists, enabling undergraduate researchers to study Burmese pythons as a means of better understanding what healthy versus unhealthy heart growth looks like.

Pythons can go 6–12 months without eating and then swallow animals as big as they are in one bite, prompting their heart to balloon 40 percent in just 48 hours. In the python’s case, this growth is healthy, much like a well-trained athlete’s heart that grows larger with conditioning.

By understanding how pythons can grow and reverse a larger healthy heart so quickly, Leinwand and her team hope to someday develop therapies that could help people strengthen or shrink their heart muscle, according to need.

Dedicated to her research, she was undeterred when told that the reptile breeder in Oklahoma City could not ship live pythons to ŷ��ڱ��Ƶ due to interstate shipping guidelines. Instead, every year, her students drive 20 hours roundtrip to buy them and bring them to her lab on campus.

Leinwand continues to mentor students and travel the country giving lectures on leadership, paying forward the gift she got from the professor in North Carolina who encouraged her pursuit of science. She prioritizes her own health too, carving out time to pedal 12 miles each night on her indoor recumbent bicycle while watching cooking shows to inspire the gourmet meals she prepares for friends.

When asked how she gets it all done (a question she hears a lot), she offers this singular piece of advice:

“Pick your battles, and don’t pick battles you cannot win,” says Leinwand. “I know how to get stuff done,” she adds with a modest shrug. “I’m happiest when I’m doing five things at once.”

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Illustration by Sol Cotti

ŷ��ڱ��Ƶ’s Leslie Leinwand helped develop the first drug for an incurable heart disease, sold two companies for billions and founded a thriving biotech institute. She’s just getting started.

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The Buzzworthy Bee Research of ŷ��ڱ��Ƶ’s Dr. Sammy

Anonymous — Mon, 04 Mar 2024 07:00:00 +0000

The Buzzworthy Bee Research of ŷ��ڱ��Ƶ’s Dr. Sammy Anonymous (not verified) Mon, 03/04/2024 - 00:00

Erika Hanes

Before Samuel Ramsey became the world’s foremost expert on bees — and an assistant professor of ecology, entomology and evolutionary biology at ŷ��ڱ��Ƶ Boulder — he was just another kid afraid of bugs. But one pivotal trip to the biology section of a local library changed Ramsey’s life forever.

“I was 7,” said Ramsey, known by most as “Dr. Sammy.” “My parents handed me a book on bugs and said, ‘People fear what they don’t understand.’ That was it.”

In opening the book, Ramsey opened a portal to another world, sparking a lifelong passion for all things creepy-crawly. Within the field of entomology, Ramsey quickly narrowed his research to bees, inspired by the many parallels between human and bee behavior.

“Take dancing, for instance,” Ramsey said. “Bees use what’s called a waggle dance to communicate. Every intricate movement and precise gesture provides vital information to the rest of the hive, such as locations for rich sources of nectar or where to build their next hive.”

Ramsey’s contributions to the study of bees have been substantial. His research encompasses various aspects of bee behavior, ecology and evolutionary biology.

One of his greatest research endeavors explores the “bee pandemic” — the mass decline of bee populations around the world — and its potential impact on our daily lives. Beyond the immediate threat to basic food crops, his research underscores the interconnectedness of the global food supply chain and the urgent need for bee conservation.

“The average person isn’t going to know there’s a problem until they see the impact on their wallets and tables,” Ramsey said. “The decline in bee populations impacts coffee, fruit, dairy and so much more. What happens when only the wealthy can afford a latte or limes? What happens when we can only buy certain fruits, nuts or vegetables seasonally? These are very real possibilities if we don’t act soon.”

As a professor, Ramsey has never forgotten his childhood lesson that fear often stems from a lack of understanding, which is why he emphasizes science communication in his classroom. Effective science communication, he argues, is not only vital for teaching but also critical for building public trust.

“If nobody can understand you, it doesn’t matter what your message is,” he said. “Unfortunately, we saw this concept play out during the pandemic — scientists couldn’t connect with the general public, even when the message was about life and death.”

Ramsey’s journey from a child afraid of bugs to an expert researcher and teacher of entomology exemplifies how knowledge can eliminate fear, and transform it into action. In and out of the classroom, Ramsey advocates for policy changes and offers practical steps that anyone can take to contribute to bee welfare.

“Refrain from using pesticides on your lawns,” he said. “Rewild your lawn by planting a garden, even a small one. Vote for representatives who will fund scientific research. You can even rehouse bees by drilling holes in a chunk of wood and placing it near plants.

“Little things can make a big difference.”

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Photo by John T. Consoli/University of Maryland

Assistant professor Samuel Ramsey's research includes bee behavior, ecology and evolutionary biology.

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Re-creating the Hand

Anonymous — Wed, 11 Nov 2020 06:00:00 +0000

Re-creating the Hand Anonymous (not verified) Tue, 11/10/2020 - 23:00

Daniel Strain

Humans do a lot of things with their hands: We squeeze avocados at the grocery store, scratch our dogs behind the ears and hold each others’ hands. These are things that many people who have lost limbs can’t do.

ŷ��ڱ��Ƶ Boulder’s Jacob Segil is working to bring back feeling to amputees' fingertips, including veterans of the wars in Iraq and Afghanistan. The biomedical engineer is an instructor in the Engineering Plus program and a research healthcare scientist at the U.S. Department of Veterans Affairs (VA).

“In my field, we have a gold standard, which is the physiological hand,” Segil said. “We’re trying to re-create it, and we’re still so far off.”

Far off, but closer than you might think. Segil is a participant in a long-running research effort led by Dustin Tyler at Case Western Reserve University and the VA. The team has used a unique neural interface and a series of electronic sensors to recreate a sense of touch for a small number of amputees who are missing their hands.

In a study published in April 2020 in the journal Scientific Reports, the group demonstrated just how effective this sensory restoration technology can be — helping one amputee experience his hand adopting a series of postures, such as a gesture resembling the thumbs-up sign.

For Segil, who recently received a $1 million Career Development Award from the VA to continue his work in ŷ��ڱ��Ƶ, the project is a chance to use his engineering skills to help people.

“As a VA researcher, your work can help people who have served our country,” Segil said. “It’s a powerful motivator.”

Photo courtesy Jacob Segil

ŷ��ڱ��Ƶ researcher aims to bring a sense of touch to amputees' hands

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Fighting COVID from the Lab

Anonymous — Tue, 07 Jul 2020 18:00:45 +0000

Fighting COVID from the Lab Anonymous (not verified) Tue, 07/07/2020 - 12:00

Twins Cara (MCDBio'11) and Amy Faliano (MCDBio'11) have been on the frontlines of the COVID-19 pandemic in the labs of the UC Health system: Cara is the coordinator of laboratory safety for UCHealth in the Denver Metro area, and Amy is a lead medical laboratory scientist at UCHealth's Highlands Ranch community hospital. Here, the sisters discuss their love for biology, what it’s like working in separate labs and the benefits of having each other.

What drew you to biology and medical testing?

Cara: Amy and I have loved science since we were little girls. Our mom used to take us to the library and we'd check out stacks of books at a time. We stayed study buddies throughout our schooling and found that biology, specifically things on the microscopic level, sparked our interest the most, so studying MCDB at ŷ��ڱ��Ƶ was an easy choice for both of us.

What was your favorite thing at ŷ��ڱ��Ƶ Boulder?

Cara: Having a Division 1 football team to support was a dream for both of us. We never missed a football game and attended a lot of basketball as well — and still love to go watch ŷ��ڱ��Ƶ play.

Amy: I loved the extracurriculars, like sports games, giving campus tours and being in ŷ��ڱ��Ƶ Collegiate Chorale.

Amy Faliano

When did you first become concerned about COVID-19?

Cara: I help manage the special pathogens unit in my hospital, so I'm always reading about infectious disease news. I would say around Christmas is when COVID-19 really started to catch my attention, because it's well-known that a SARS-like or flu-like respiratory illness would be the next "pandemic" and this seemed mysterious enough to fit the bill.

What COVID-related questions have you been getting most from friends and family?

Cara: We're getting a lot of questions about how the testing works, which is great! Lab testing and medical laboratory science has always been one of the less-talked-about fields in the medical world, so it's been great to have a spotlight shined overall on the great work that clinical labs do to support patient care.

Amy: A lot of friends and family who have reached out had questions about how the testing is performed, what the results look like. One of my aunts just had to know if the novel coronavirus really looks like the "spiky ball' picture she has seen on the news. The answer is yes, that is what it looks like under an electron microscope.

Cara Faliano

What has it been like working through this difficult time?

Cara: Like anyone in healthcare would say, this has been a very tiring and trying couple of months of hard work, rapid changes and adapting to the situation as it develops. I've personally been involved on the more administrative side of the laboratory, so I've re-written the lab's "COVID-19" procedure more times than I can count, have been tasked with things like helping to create drive-thru testing locations, have had to find creative new inventory for the lab to use in supply chain shortages — like 3D-printed swabs — and have been managing the inventory of testing supplies for the entire hospital system. Everyone is wearing many hats in this pandemic, and it's been a scramble for all in the lab.

Amy: I am a leader in the laboratory at UCHealth Highlands Ranch Hospital, a community hospital in the UCHealth system. I had to quickly validate new testing for COVID-19, train all staff and figure out how to balance that testing with all of our normal testing for patients seen at our hospital and clinic. It was stressful to have to get the validation paperwork and new procedures at a rapid pace, and I have worked a lot of long hours.

You both worked in blood banks during the 2012 Aurora movie theater shooting. What was that like?

Amy: We both got called into work the night of the shootings and came to the hospital blood bank right away. That was a crazy night of assisting in testing and preparing blood products for a mass-casualty situation, but definitely affirmed my decision to go into the career field. What the hospital laboratory does is so important, and this pandemic is another reminder of that.

How has having each other been therapeutic?

Cara: My work on the admin side directly impacts Amy in her lab, as her lab follows the procedures I've written and uses the same materials, so we've been able to brainstorm together on some things or bounce questions off of each other.

Amy: Through the stress of the pandemic it was nice to have someone who was there for me, and understood how hard it was to have to continue working as if things were business as usual. Cara understood how physically and mentally exhausting it was to have to work hard and work long hours. I needed her to vent to, but also to inspire me to go work hard again the next day since we were in this together.

Both of you went to the same university, same degree, same career field — just how competitive are you two?

Cara: Neither of us have a competitive bone in our bodies! We've always been really supportive of each other and want the other to do well.

Amy: I agree with that! It makes sense that we ended up in similar careers since our love of science has always been the thing that bonded us. I think we used our different strengths to find our niches in the career field, no competitiveness there.

What's one common misconception about being a twin?

Cara: I think people sometimes love to assume that we do everything together since we're in the same career field. We've rarely worked directly together, and have our own lives and interests outside of work. We're just like any other really close friends!

Amy: I don't think twins are that different from any other siblings who are close.

Interview condensed and edited.

Photo courtesy Cara Faliano

Twins Cara and Amy Faliano have been on the frontlines of the COVID-19 pandemic in the labs of the UCHealth system.

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Healthcare at Home

Anonymous — Mon, 01 Jun 2020 17:40:00 +0000

Healthcare at Home Anonymous (not verified) Mon, 06/01/2020 - 11:40

Christie Sounart

ŷ��ڱ��Ƶ Boulder computer science assistant professor Mirela Alistar wants to make healthcare more personal. Her work with microfluidic biochips is getting us there. Here, the director of the ATLAS Institute’s Living Matter Lab discusses her biochips, in-home testing and melding science with art.

What brought you to ŷ��ڱ��Ƶ?

I was ready to start my own research group, so I embarked on an exciting journey of applying to more than 100 universities for a faculty position. While interviewing all over the world, I was impressed with the interdisciplinarity of ATLAS Institute, with ŷ��ڱ��Ƶ’s ambition and drive to support young faculty and with Boulder’s natural beauty and progressive culture. Needless to say, choosing ŷ��ڱ��Ƶ Boulder was the easiest decision I ever made.

What is your main intention with the Living Matter Lab?

As the name says, I am interested in living matter, especially in its non-human form. In the Living Matter Lab, we explore the connection between humans and the life around us by focusing on personal healthcare. Specifically, we are investigating how far we can push healthcare into the hands of people by the means of technology. To do this, we develop biochip instruments that can be used at home by people for various medical applications.

Can you describe these instruments?

Biochips are small electronic devices that manipulate droplets of fluids by executing bio-protocols — programs that move, split and mix droplets containing chemical compounds (reagents). Biochips automate processes traditionally performed in wet labs. The key advantage of biochips is that they are adaptable, thus capable of running different bio-protocols. Instead of going to a specialist, a patient can download a bio-protocol.

Why do we need biochips?

Microfluidics is the engineering that figures out how to manipulate fluids in very small amounts, at micro level. You see, fluids at large scale — the coffee in your cup, the water coming from the tap — behave very differently than when in very small amounts. To give you an idea of how small we are talking, the size of a rain droplet is about 20 microliters [one-millionth of a liter] and that is around the maximum size approached with microfluidics. Such tiny amounts of fluids are hard to manipulate because they have a strong surface tension that has to be overcome. Biochip instruments are able to manipulate such droplets in the picoliter [a trillionth of a liter] range.

What sort of tests might people perform with these?

Biochips have been shown to be able to perform basic tests, such as detecting the glucose levels on physiological fluids such as blood, saliva, urine and serum. We are working on developing a procedure that allows biochips to test for bacterial and viral infections.

Mirela Alistar

Could these biochips detect coronaviruses or other viral infections?

I am working on developing biochips that can perform ELISA [enzyme-linked immunosorbent assay], a standard procedure used to detect viral infections. ELISA is currently used as one of the methods of testing for [the novel] coronavirus. We do hope during the next year we will have a biochip that can run ELISA, and that means it will be able to detect various viral infections. I am also aware and even had collaborated with other research labs working on the same problem. However, even if any of us are successful in developing such biochips, they will still need quite a few years of development until approved to be used as a diagnosis tool.

What do you see them being used for the most initially?

I foresee a progressive roadmap for biochips, where they first will be adopted by doctors as an effective way of performing quick tests, an essential step in differential diagnosis. Then, I see a lot of potential for biochips to be used in mobile settings, such as during traveling or outdoor activities. Finally, biochips will empower patients to perform selected tests at home, as part of their decision whether to see a doctor.

How could these change our healthcare system?

Similar to how mobile computing has enabled over 60% of the population to solve a wide range of problems by means of software, I believe that biochips will change how people interact with a wide range of healthcare processes. In the long run, I believe biochips will lead to democratizing healthcare, and to a process that moves away from the current ‘one size fits all’ concept towards more personalized care.

Are there non-health uses for these biochips?

Yes, for example, researchers at University of Washington forked one of our older biochip devices and are using it for DNA computing. That means they embed DNA inside the droplets and use the droplet mixing and splitting to perform operations on the information contained in the DNA. I am also aware of people that replicated our biochips to use them for perfume mixing. One of the students in my class is designing a biochip that tells the time, basically a clock with fluids.

What other things are you working on right now?

Apart from personal healthcare, we have a second angle to approach our work in the Living Matter Lab. This angle is an artistic one, where we explore and design interactions and tangible interfaces between humans and non-human life. Examples of current projects include designing an escape room where humans and dinoflagellates [algae] collaborate to find the exit, developing do-it-yourself spirulina bioreactors for at-home use and inventing biomaterials that allow kids to grow their own toys and people to ‘cook’ their own clothes.

What do you do outside of your work?

I am focused right now on building a strong community in Boulder that engages in sci-art and bio-art. I would love to see science, technology and art coming together in interactive installations and performances available to the public at large.

Interview condensed and edited.

Illustration by TheiSpot/ Keith Negley

ŷ��ڱ��Ƶ Boulder computer science assistant professor Mirela Alistar wants to make healthcare more personal. Her work with microfluidic biochips is getting us there.

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Q&A: Why We Should Care ŷ��ڱ��Ƶ Soil Biodiversity

Anonymous — Wed, 16 Oct 2019 16:46:14 +0000

Q&A: Why We Should Care ŷ��ڱ��Ƶ Soil Biodiversity Anonymous (not verified) Wed, 10/16/2019 - 10:46 Ula Chrobak

Kelly Ramirez (PhDEbio’12) on how understanding microbial ecology can help solve global problems of hunger, land degradation and climate change.

When we think about biodiversity, many of us imagine charismatic animals like polar bears or vibrant ecosystems like the rainforest. But a fundamental type of biodiversity is far less visible —the microbes, small invertebrates and other creatures that inhabit the soil. Places we might not imagine as biodiversity hotspots, like New York City’s Central Park, are home to a vast foodweb of thousands of organisms, many of which support the cycling of elements that makes this earth habitable.

ŷ��ڱ��Ƶ Boulder alumna Kelly Ramirez, soil microbial ecologist at the Netherlands Institute of Ecology, is trying to learn more about the role of these underappreciated ecosystems. Outside her research, she’s also involved with the increasing the visibility of women scientists, through her organization, 500 Women Scientists.

How do you define soil biodiversity?
Soil biodiversity is all the microbes, earthworms, even moles that contribute to creating an ecosystem that cycles nutrients, supports plant life, food, water — pretty much all the things terrestrial ecosystems rely on.

Why is soil biodiversity important?
Fundamentally, it’s important to help plants grow. We wouldn't have a green earth without brown soil. Soil stores carbon, cycles water, cycles nutrients. Soil is included in all the ecosystem services that are necessary for humans to be on Earth.

We wouldn't ask that same question of why are plants important. It’s just not as obvious, because we can’t see soil organisms functioning, whereas we can see a tree growing, we can see corn growing and then it produces food.

What sparked your interest in soil biodiversity?
When I was doing my bachelor’s degree, I kept taking microbiology and virology classes and I was convinced that I was gonna go to medical school. My virology class had a teacher who had one of those old slide projectors and it was just story time for an hour and a half twice a week.

Then I took an ecology class and the concepts of ecology were also really cool, and they had a whole different framework. In ecology, especially when you think about microbes, there's this whole frontier of so many questions.

So I looked for graduate programs that had microbial ecology. I found Noah Fierer [at ŷ��ڱ��Ƶ Boulder] and he was studying microbial ecology in the soil. I was really inspired and motivated by his work and he invited me to his lab.

I was really interested to study microbes and what they do in any ecosystem. You can ask very similar questions whether you’re in the soil or studying microbes on leaves, caterpillar guts, or water. As I finished my PhD I was like, Ok, we have all this data about microbes, but what can we actually do with it? It doesn't help save the environment, combat climate change, or restore ecosystems if we just have a list of microbial species.

So, I started a postdoc with Diana Wall at ŷ��ڱ��Ƶ State in 2012 to bring this really important research that people were doing with soil organisms into the management and policy world. There's conservation work for plants and animals, but that's not a thing in the microbial world. We still have so many questions. How do you restore a soil to have a microbial community that you want? Well, we don't even know what the community would look like.

You were the executive director of the Global Soil Biodiversity Initiative between 2012 and 2014. What did you do there?
It was really fun. The goal was to link researchers and research across soil biodiversity. I created a network of people working on microbes, on earthworms, on tardigrades [a group of eight-legged microscopic animals] — on anything to do with soil biodiversity. We try to promote and amplify their research. We would go to conferences directed at policymakers, bringing in these stories of soil biodiversity to say ‘Hey, there are these organisms out there that have been largely forgotten in biodiversity estimates in the world.’

One way we highlighted those organisms that was with a research project. We went to Central Park and we collected soil samples to look at what the biodiversity was. There’s like 150,000 types of bacteria in the soil, and 70,000 types of fungi, earthworms and tardigrades. That was interesting research, but it also was a great talking piece. I can talk to anyone about Central Park. And then the number of organisms that occur in the soil just in Central Park is really astounding.

The other part was getting people together to talk about the steps that we have to take to translate research so it actually can be used in policy.

Are you still involved with the organization?
Yes. We're working on a project together to push the discussion about the topics that soil biodiversity needs to be more present in for these global agendas, like the UN Sustainable Development Goals.

What questions are you trying to answer in your research?
Lately I’ve been thinking a lot about the role the microbes have in helping plant establishment, success and productivity. Just like the human microbiome, it’s thought that there is an important core microbiome for plant communities. But my work is showing that it’s really variable based on the plant species.

We've been looking at range expansion. When an ecosystem gets warmer or drier and plants move there or leave, do they bring along their microbes? Or do they find new microbes?

Another area of research that I’m interested in is carbon cycling in the soil. We know that microbes and soil biodiversity are intimately connected to the cycling and storage of carbon in the soil, but how does that change across different land uses? As land is used more and more for agriculture, can they store as much carbon in the soil? And are there ways to help restore the biodiversity in the soil to increase carbon storage? These are tricky questions because it’s not like we're just going to add more of this one type of this bacteria and that still solve everything. It’s a lot more complex than that.

That does sound complicated. What keeps you motivated to do this research?
The questions in ecology are one thing, but the questions of solving global hunger or climate change are really serious, so if my research can even a little bit inform on that, that would be really great. What motivates me is balancing my research questions with important global sustainability questions, and figuring out ways that my research can fit into those questions.

This year I went to the Convention on Biological Diversity conference in Egypt, COP14. I presented about soil biodiversity, but I also just got to listen to people from all over the world talk about the challenges that their countries face with land degradation and agriculture and the solutions that they're applying. It's really inspiring for me so sit in on those.

What’s your favorite soil organism?
I love bacteria, but the most cuddly organism is the tardigrade. Everyone loves it. We always use it in photos to convince people that soil has cuddly organisms.

What have you been working on recently with 500 women scientists?
We now have over 10,000 women who have signed up on our Request a Scientist database. There’s this idea that there aren’t any good women in this field. But there are a lot of great women scientists, it’s just that they're not usually asked to do things. We have some funding to rebuild that database so that we can have more than the 10,000 women that we have in there right now.

The other thing we're working on that I'm really excited about is that we are developing a fellowship for women of color leading in STEM.

And then we're still building up our international network of women scientists with our local chapters that we call pods. We have over 300 pods around the world. We also amplify their work, because a lot of them are doing awesome work in their communities.

Condensed and edited by Ula Chrobak

Kelly Ramirez (PhDEbio'12) on how understanding microbial ecology can help solve global problems of hunger, land degradation and climate change.

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Blowing the Doors Off the Microbial World

Anonymous — Fri, 01 Mar 2019 07:00:00 +0000

Blowing the Doors Off the Microbial World Anonymous (not verified) Fri, 03/01/2019 - 00:00

Lisa Marshall

Photo by Glenn Asakawa

ŷ��ڱ��Ƶ's Norm Pace isn't intimidated by the darkness of remote caves, or the vastness of the microbial universe. He's mastered both.

Norm Pace can still remember what it smelled like in that first cave.

The year was 1957. The place, Monroe County, Indiana.

The boy, a precocious 14-year-old who had talked his way into the local caving club’s expedition to the newly discovered Monroe Cave.

After ducking through a hidden entrance, climbing down 20 feet and slithering on his belly for a quarter-mile, young Pace stood up to behold a room full of 40-foot rock formations coated in a white crystalline substance known as “moon milk.”

“It smelled wet, mucky and alien in there,” said Pace, now a ŷ��ڱ��Ƶ distinguished professor emeritus of molecular, cellular and developmental biology. “It was clear that this was not a world like the one I was used to.”

Pace has since discovered and mapped some of the largest and most dangerous caves on the planet, a hobby that has required him to traverse deep underground lakes in a wetsuit and scuba gear, rappel down waterfalls and narrowly escape death.

Among cavers, he is a legend.

But he is best known for his exploration of a different once-alien terrain: The world of microbes.

A recent National Academy of Science honoree for his “pioneering work on methods for delineating the diversity of life on Earth,” Pace is credited with developing gene sequencing tools that have made it possible to identify virtually all microorganisms, wherever they live — remote caves, ocean floors, inside our own bodies. The current boom in microbiome research (the study of the myriad bugs living in, on and around us) wouldn’t have been possible without him, colleagues say. And thanks in part to his work, the microbial “tree of life” as we know it is rapidly filling in.

“Microbiology is going through a Golden Age right now, and it is largely because of Norm,” said Hazel Barton, a University of Akron scientist who once worked in Pace’s lab. “He revolutionized the field.”

A Renaissance in Science

When I meet Pace at his ŷ��ڱ��Ƶ office, he greets me with a cold fist bump. He bumps fists with everyone: After decades of studying microorganisms, he knows too well what’s on people’s fingers. His fist is cold. Though it’s November and already dark, he rode his bike to meet me.

At age 76, he has started riding again, not long after surgery to remove several brain tumors and starting a new immunotherapy for Stage 4 melanoma.

He is in clinical remission. He thanks science.

“There is an incredible renaissance occurring in science right now,” he said. “The fact that I am even sitting here talking to you right now is evidence of that.”

Another scientific renaissance was underway during Pace’s rural Indiana childhood.

After his parents bought him a microscope kit, he spent hours poring over the strange rods and spheres. At 15, after building his own chemistry lab, he ruptured his ear drum and shattered the surrounding bones in a mishap with a batch of silver fulminate.

“Still can’t hear out of it,” he said.

The only way to study microorganisms was to grow them in petri dishes. Pace would find a better way.

Pace’s formal entrée into science came in 1957, after the Soviet Union launched the Sputnik satellite. The U.S. government took note of the competition and launched two-week camps to engage kids in science. Pace was brought to Indiana University, where he met a molecular biologist. He was hooked.

“We didn’t know a whole lot about the natural microbial world,” he said.

Insects dominated textbooks then. Microorganisms appeared only in the contexts of “disease and rot,” he said. And the only way a scientist could study a microorganism was to grow it in a petri dish and observe its physical traits under a microscope.

This was problematic, because only a miniscule fraction of microbes will actually survive in a lab.

“If you couldn’t culture it, you couldn’t identify it,” he said.

Pace would find a better way.

Filling in the Tree of Life

He attended Indiana University and the University of Illinois before ultimately making his way to ŷ��ڱ��Ƶ in 1999.

For years he studied ribosomal RNA, the molecules that form the protein-making machinery of cells. His friend Carl Woese taught him that by comparing rRNA between organisms, one could infer a lot about how they evolved and the relationship between them.

Pace ran with the idea:

What if, rather than trying to grow a patch of some unknown microorganism in a lab to study it, you just sucked a bit of RNA from it in its environment, sequenced the genes, and compared them to those of other known organisms already plotted on the tree of life?

It was all about measuring the difference, or distance, between things, he said — kind of like mapping a cave. Pace first tried it with some mysterious pink filaments he and students scooped from a bubbling cauldron in Yellowstone National Park.

The resulting paper, published in 1984 in Science, made history, marking the first time anyone identified an organism by sequencing its genes.

Biologists now had a way to study microbes that wouldn’t grow in labs.

“We went from not recognizing 99.9 percent of the microbes out there to having the ability to identify everything,” said Akron’s Barton.

Since then, Pace has used genetic sequencing to discover communities of bacteria from the New York City subway, household showerheads and inside the intestines of a Russian surgeonfish (where he discovered the world’s largest bacterium, Epulopiscium fishelsoni).

Scientists worldwide have followed.

In the mid 1980s, all known bacteria fit into about a dozen groups, or phyla. Today, there are about 150. Entire conferences are dedicated to the microbes living in our gut.

How many species are there?

“How many stars are in the sky?” said Pace. “It’s one of those wonderful unknowables.”

Mapping the Unknown

The same could be said for the world’s caves, which, thanks to Pace’s hobby, we also understand better now.

Because GPS is hard to use underground, mapping a cave requires old-fashioned exploration: “You have to physically move through it and measure angles and distances,” said Barton, a fellow caver.

For Pace, this has made for great adventures.

Photo courtesy Norm Pace

At ŷ��ڱ��Ƶ’s Spring Cave, he had to don full scuba gear, wear it as he scaled a waterfall, then drop into an underground river and swim, the water lit only with a headlamp, for 300 feet.

In a cave near Grenoble, France, he broke ribs when his backpack slipped, smashing him against a rock wall.

During one harrowing expedition through a Mexican cave, he was making his way down a wall near a frigid waterfall when the clip holding his rope popped open, hurtling him downward into the torrent until the rope caught him 30 feet below. He dangled upside down for minutes, cold water rushing over his head, before freeing himself. His fellow cavers thought he was dead.

“I actually went through the mental process of dying,” said Pace, who led his last cave expedition in 2016. “That was interesting.”

Mortality called again in 2017, when he had a seizure while preparing for a lecture. “When I heard Stage 4 melanoma, I figured, ‘F#$@, I’m outta here’” he said.

But after 18 months on the immunotherapy drug Keytruda, he’s reinventing himself.

He recently remarried his former wife, Bernadette, a professional trapeze artist, he’s on the lecture circuit, and though he’s closed his lab, he teaches occasionally.

His protégés describe him as intimidatingly smart, at times cantankerous and extraordinarily generous.

“I am where I am today because of him,” said ŷ��ڱ��Ƶ School of Mines professor John Spear.

Each year, around Nobel Prize season, former students cross their fingers and whisper Pace’s name.

He’s humbled, but not holding his breath.

After he’s gone, he has just one wish:

“I want to be remembered as the guy who blew the door off the microbial world.”

Comment on this story? Email editor@colorado.edu.

ŷ��ڱ��Ƶ's Norm Pace isn't intimidated by the darkness of remote caves, or the vastness of the microbial universe. He's mastered both.

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First of Fly: Drosophila Research and Biological Discovery

Anonymous — Fri, 14 Dec 2018 22:09:30 +0000

First of Fly: Drosophila Research and Biological Discovery Anonymous (not verified) Fri, 12/14/2018 - 15:09

By Stephanie Mohr (PhDMCDBio’99)
(Harvard University Press, 272 pages; 2018)

Buy the Book

A single species of fly, Drosophila melanogaster, has been the subject of scientific research for more than one hundred years. Why does this tiny insect merit such intense scrutiny?

Drosophila’s importance as a research organism began with its short life cycle, ability to reproduce in large numbers, and easy-to-see mutant phenotypes. Over time, laboratory investigation revealed surprising similarities between flies and other animals at the level of genes, gene networks, cell interactions, physiology, immunity, and behavior. Like humans, flies learn and remember, fight microbial infection, and slow down as they age. Scientists use Drosophila to investigate complex biological activities in a simple but intact living system. Fly research provides answers to some of the most challenging questions in biology and biomedicine, including how cells transmit signals and form ordered structures, how we can interpret the wealth of human genome data now available, and how we can develop effective treatments for cancer, diabetes, and neurodegenerative diseases.

Written by a leader in the Drosophila research community, First in Fly celebrates key insights uncovered by investigators using this model organism. Stephanie Elizabeth Mohr draws on these “first in fly” findings to introduce fundamental biological concepts gained over the last century and explore how research in the common fruit fly has expanded our understanding of human health and disease.

Stephanie Mohr’s (PhDMCDBio’99) book First in Fly: Drosophila Research and Biological Discovery, was included in Smithsonian magazine’s list of Ten Best Science Books of 2018. The book was published in March 2018 by Harvard University Press. Stephanie is the Director of the Functional Genomics Resource Lab at Harvard Medical School, where she is also a lecturer on genetics.

A single species of fly, Drosophila melanogaster, has been the subject of scientific research for more than one hundred years. Why does this tiny insect merit such intense scrutiny?

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The Bee Counters

Anonymous — Mon, 01 Dec 2014 17:15:00 +0000

The Bee Counters Anonymous (not verified) Mon, 12/01/2014 - 10:15

Holly Hickman

ŷ��ڱ��Ƶ has one of the nation's most diverse bee fauna. An army of volunteers is helping ŷ��ڱ��Ƶ scientists track hundreds of front range species.

When a phenomenon called colony collapse disorder began ravaging honey bee populations in the mid-2000s, the world took notice: Flowers, food crops and ecosystems depend on bee pollination.

Of late, mass colony collapse has moderated in the United States, but honey bees’ long-term population trend is still sharply downward. And there are thousands of other bee species about which little is known because they get less attention. ŷ��ڱ��Ƶ alone is home to 946 species, more than all but four other states.

Their circumstances are not assumed to be good, based on existing surveys.

“In general, bee populations are considered to be in decline everywhere,” says Virginia Scott, entomology collections manager at the University of ŷ��ڱ��Ƶ Museum of Natural History in Boulder.

To learn more about ŷ��ڱ��Ƶ’s abundant solitary wood nesting bees, which make up about 25 percent of all Front Range species — and to lay a foundation for scientific assessments of population changes — Scott and colleague Alexandra Rose in 2013 established The Bees’ Needs, a research project involving hundreds of volunteer “citizen scientists.”

“We want to understand the ‘other’ bee mystery,” says Rose, a bird biologist who is the museum’s program manager for citizen science.

Counting bees isn’t easy: Small and spry, they can live throughout a vast area.

“Some are the size of gnats,” says Rose.

“You’d think they were fruit flies.”

Also, the Front Range is home to a great diversity of bees, about 650 species, or more than two-thirds of all ŷ��ڱ��Ƶ species. (Only the desert states of California, Arizona, New Mexico and Utah have more.) Learning something about them all requires a small army.

The Bees’ Needs’ volunteers — 528 in 2014, up from 337 a year earlier — don’t need advanced science training. Mainly, Scott says, they need to be diligent observers and recorders.

“I suppose patience helps, too,” she says.

A goal of The Bees’ Needs is establishing baseline populations for as many species as possible.

These will provide a basis for comparison in the future.

To make data collection convenient, the museum provides volunteers with nesting boxes similar to birdhouses — stationary attractions where bees (and wasps) take shelter and deposit identifying traces.

The first year of the program, Rose, Scott and friends drilled 10,000 holes of varying sizes into each of 250 wooden boxes.

Volunteers install the boxes in sunny spots (shady ones attract earwigs) and track nests bees build there, noting the plugs mother bees put into the holes to protect their larvae. Different species use different plug materials — resin, for example, or chewed leaves, grass, mud or silk. Volunteers check the nests every two weeks from April to October, taking pictures and reporting on nest materials.

Adult bees die after the first hard frost. In the spring, offspring chew through the plugs to enter the world outside.

“It’s fun, especially as you get others involved,” says volunteer Sandra Laursen, a researcher in ŷ��ڱ��Ƶ’s ethnography & evaluation research unit.

Last year Laursen hung her nesting box on the fence of her Boulder condominium complex and found that the box’s “apartments” especially appealed to children.

“One ten-year-old boy quite liked it when he had spotted something I hadn’t,” she says.

So far, nobody’s been stung (or said so, anyway), according to Rose — not even by the wasps that also take advantage of the boxes for nesting.

Wasps engender less fondness than bees — “We discovered early on that wasp is a four-letter word,” says Scott — but they too are important pollinators. Solitary wasps harvest aphids, caterpillars and other garden pests. Rose calls them “the unsung heroes of the gardening world,” noting they pollinate flowers along the way: “Talk about organic gardening!”

Rose soon expects to finish analyzing the citizen scientists’ 2013 data sets. This will yield initial baseline populations for many ŷ��ڱ��Ƶ bee and wasp species. Data sets collected in the years ahead will help reveal population changes.

“This is a long-term project,” Scott says. “The more cumulative data we can collect, the more we’ll understand the mysteries of these solitary insects.”

To volunteer for the 2015 Bees’ Needs project, visit beesneeds.colorado.edu/.

Photo courtesy ŷ��ڱ��Ƶ Museum of Natural HIstory (bee); Diane Wilson (bees on flowers)

ŷ��ڱ��Ƶ Bees: A Sampler

Common name: Cuckoo leaf-cutting bee
Scientific name: Coelioxys sp.
Looks like: White stripes, pointy abdomen
Size: 1/2″

Common name: Mason bee
Scientific name: Hoplitis albifrons
Looks like: Jet black, elongate, patches of pale hairs
Size: 5/8″

Common name: Green mason bee
Scientific name: Hoplitis fulgida
Looks like: Bright metallic green or blue-green, elongate
Size: 1/2″

Common name: Masked bee
Scientific name: Hylaeus leptochepalus
Looks like: Shiny, black, nearly hairless with ivory marking on face, legs
Size: 1/4″

Common name: Leaf-cutting bee
Scientific name: Megachile sp.
Looks like: Fuzzy
Size: 5/8″

Common name: Pugnacious leaf-cutting bee
Scientific name: Megachile Pugnata
Looks like: Gray, large-head, white stripes on elongate abdomen
Size: 3/4″

Common name: Mason bee
Scientific name: Osmia sp.
Looks like: A fly; rotund, metallic blue
Size: 3/8″

Common name: Cuckoo bee
Scientific name: Stelis rudbeckiarum
Looks like: A stocky wasp, bald, black with yellow stripes
Size: 5/16″

ŷ��ڱ��Ƶ has one of the nation's most diverse bee fauna. An army of volunteers is helping ŷ��ڱ��Ƶ scientists track hundreds of front range species.

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Winter 2014

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Biology

Leslie Leinwand & The Science of Getting Things Done

Healing a big, sick heart

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