Biochemistry

Scientist gleans human lessons from bacterial immune systems

Anonymous — Fri, 01 Mar 2024 18:56:40 +0000

Scientist gleans human lessons from bacterial immune systems Anonymous (not verified) Fri, 03/01/2024 - 11:56

Rachel Sauer

CU Boulder PhD student Emily Kibby has won the Harold M. Weintraub Graduate Student Award in recognition of her work researching bacterial immune responses

There are certain advantages to being a one-celled organism with no nucleus. In general, reproduction happens fast, and thus evolution does, too.

Take bacteria, for example: A bacterium can be invaded by a phage, which is a virus that infects and replicates only in bacterial cells, and within several generations—which can emerge in a single day—the bacteria may have evolved immunity to that virus.

“We’re so evolutionarily outclassed by bacteria,” says Emily Kibby, a PhD candidate in the University of Colorado Boulder Department of Biochemistry and member of the Aaron Whiteley Research Group. “They can evolve so much faster, and they’re the real biochemical innovators of life on this planet. I think we have so much to learn from them.”

CU Boulder PhD candidate Emily Kibby has been recognized with the Harold M. Weintraub Graduate Student Award for outstanding achievement during graduate studies in the biological sciences.

In fact, since joining Whiteley’s research group in 2020 for her graduate studies, that’s exactly what Kibby has done—work to understand how eukaryotes (organisms whose cells contain a nucleus encased in a membrane), including humans, have acquired and adapted bacterial immune proteins for their own purposes.

Her work recently was recognized with the Harold M. Weintraub Graduate Student Award, given by the Fred Hutch Cancer Center to honor outstanding achievement during graduate studies in the biological sciences. Kibby and her fellow winners were chosen for the quality, originality and scientific significance of their research and will be honored at a symposium May 3 in Seattle.

“Emily is highly deserving of the Weintraub award because she is a dedicated scientist whose fearlessness and innovative thinking have allowed her to open new research areas in my lab,” says Aaron Whiteley, a CU Boulder assistant professor of biochemistry.

“One of the most impressive aspects of her thesis work was a decision in her fourth year to undertake a new project in computational biology. She demonstrated independence and resourcefulness, seeking out necessary expertise from other investigators and in the literature. It can be very hard to break into new disciplines, and I am extremely proud of her accomplishments. I expect nothing short of amazing things to come!”

Bacterial origins

Kibby credits excellent AP biology and AP chemistry teachers at her Wisconsin high school with nurturing her ever-growing interest in science. It also helps that both of her parents are teachers, she says.

So, when she was considering what to study as an undergraduate at Swarthmore College, “I decided to head down the middle between biology and chemistry,” she says. “I’ve just always been fascinated by the molecular mechanisms that make life possible. We have this incredible amount of molecular detail on cellular processes, but there’s still so much more to learn. That’s always what’s been so exciting to me, that we know so much but there’s this vast amount still to learn.”

She fell in love with bacteria during her undergraduate summers working in Helen Blackwell’s lab at the University of Wisconsin-Madison, where an aim is to devise novel chemical tools to decode and interfere with bacterial communication pathways.

After joining the Whiteley Lab, Kibby delved into research about bacterial immune systems and host-pathogen interactions. In studying the constant conflict between bacteria and phages, Kibby explored the wide range of immune pathways bacteria use to counter phage infection.

Kibby and her research colleagues homed in on proteins containing a NACHT module, which are present not only in prokaryotic bacteria, but in eukaryotic cells as well. These genetic overlaps demonstrate that elements of the human immune system originated in bacteria, Kibby says.

I’ve just always been fascinated by the molecular mechanisms that make life possible. We have this incredible amount of molecular detail on cellular processes, but there’s still so much more to learn."

“Rather than NACHT modules evolving out of thin air, it’s more likely they came to us from bacteria,” she explains. “At some point early in the history of human evolution, an ancient eukaryote interacted with a bacterial cell that had evolved this type of immunity and was able to adopt that for its own protection.”

The incredible diversity of bacteria

After four years of research, Kibby and her colleagues published their findings about how these bacterial proteins protect against phage. She then pivoted to research using AlphaFold Multimer to predict protein-protein interactions: “I shifted to this new approach in part because our mammalian NACHT proteins that have this great example of recognizing specific proteins,” Kibby says. “So, I thought I would learn something new and see if I could use computational tools to predict similar interactions in bacteria.”

AlphaFold Multimer is a tool that emerged from Google DeepMind, one of Google’s artificial intelligence think tanks, and has proven extremely good at predicting the structures of proteins from just an amino acid sequence, for example. It also can predict the interactions between multiple different proteins.

After learning the computational underpinnings of these predictions, Kibby is now doing lab work with actual proteins to determine whether the predictions are correct—do the proteins actually do what the computer says they will?

“I hope what we’re doing now helps set a standard for how to integrate protein predictions with wet lab validation,” Kibby says. “AlphaFold Multimer is really just another screening tool. It’s amazing and it’s shattering all the barriers of what we had been able to do before, but you will always have to have your controls and always have to validate your hits.”

In the midst of this research, Kibby hopes to defend her thesis in September and receive her PhD in December. She then aims to do postdoctoral research and ultimately earn a role at a university that allows her to research and teach, because guiding people through the fascinating universe of bacteria is one of her passions.

“The way I explain it is, everything is infected by viruses, and we have evolved number of ways to protect ourselves from these threats,” she says. “A lot of times, we think of bacteria as threats to our own immune system, and that’s true, they can be. But bacteria are also threatened by virus, and just like us, to protect themselves they have also evolved immune systems.

“If you look at CRISPR, for example, it’s revolutionizing medicine and research, but in the wild CRISPR is a bacterial immune system that protects bacteria from phages. There are very practical human applications for understanding the incredible diversity of bacteria.”

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CU Boulder PhD student Emily Kibby has won the Harold M. Weintraub Graduate Student Award in recognition of her work researching bacterial immune responses.

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Biochemist wins Cogswell Award for Inspirational Teaching

Anonymous — Fri, 23 Feb 2024 23:51:37 +0000

Biochemist wins Cogswell Award for Inspirational Teaching Anonymous (not verified) Fri, 02/23/2024 - 16:51

Amy Palmer, professor of biochemistry, recognized for revamping classroom experiences, championing diversity and striving to connect with students ‘beyond the course curriculum’

Amy Palmer, a biochemistry professor at the University of Colorado Boulder, has won the 2024 Cogswell Award for Inspirational Instruction.

Supported by a generous donation from Craig Cogswell, a three-time alumnus of CU Boulder, the award recognizes outstanding instruction in the college, honoring individuals for their inspirational qualities and teaching abilities.

Palmer, who is faculty director of the Honors Program, joined the CU Boulder faculty in 2005. She holds a bachelor’s in chemistry from Dartmouth College, a master’s in education from Stanford University, and a PhD in biophysical chemistry from Stanford.

Amy Palmer (second from left), a CU Boulder professor of biochemistry and the 2024 Cogswell Award winner, met with students in Mumbai, India, in January. (Photo: Amy Palmer)

In letters of nomination, her students and colleagues praised her for adopting state-of-the-art science-teaching methods, launching a new biochemistry seminar course for first-year students, transforming how traditional courses are taught, and advancing the diversity of student populations.

Moreover, they said she genuinely cares about students, striving to get to know them personally and “connect with them beyond the course curriculum.”

“Professor Palmer is a phenomenal teacher and universally praised by students from all levels at CU for her outstanding teaching pedagogy, her commitment to students and her inspirational character,” four of her colleagues wrote.

In his nomination letter, one former student said: "The dedication she demonstrates through meticulously planned lessons, coupled with a dynamic teaching style, makes her classes both enjoyable and academically enriching. What truly distinguishes Amy is her inspirational impact on students. She goes beyond imparting knowledge; she instills a sense of curiosity and a desire for academic excellence. Amy's passion for the subject matter is infectious, motivating students to explore beyond the confines of the curriculum and develop a deeper understanding of the material."

A dedication to teaching

Another former student, now a PhD candidate at Harvard University, wrote that Palmer had inspired her inside and outside of the classroom. Several connections and collaborations resulted from Palmer’s “admirable generosity with her time,” the student said, adding:

“When I first met Professor Palmer, I was primarily interested in pursuing a career in medicine, but after engaging with Dr. Palmer and hearing about her training and current career, I was inspired to consider and ultimately pursue further training in academia. The lasting impact of Dr. Palmer’s guidance and inspiration on my training as a scientist cannot be overstated; it drives me forward still today.”

Teaching and mentoring students are two of my career passions. The opportunity to work with undergraduates and try to transform how we teach science is what drove me to become a professor. It is so rewarding to hear from students that this has had an impact on them.”

Given her accomplishments and praise from such students, her colleagues said, “It is no wonder that Professor Palmer is one of the most admired faculty members among our student body.”

Palmer said she was “deeply touched and honored” for both the nomination and the award. “Teaching and mentoring students are two of my career passions. The opportunity to work with undergraduates and try to transform how we teach science is what drove me to become a professor. It is so rewarding to hear from students that this has had an impact on them.”

Cogswell earned a bachelor’s degree in history in 1970, followed by master’s degrees in education in 1979 and in educational psychological studies in 1984.

Cogswell retired from a long career as a high school social studies teacher, corporate educator and young-teacher mentor. He was named Colorado Teacher of the Year in 2000.

“I think university instructors always have the dilemma that their primary focus is research or writing, things like that,” he told the Colorado Arts and Sciences magazine in 2017. “To me, at the university level, when someone really works hard on being a dynamic, interesting or challenging teacher, that is something that should be acknowledged and rewarded.”

He said he is “overwhelmed” by the Palmer’s record, adding: “Professor Amy Palmer richly deserves the recognition. She is clearly a knowledgeable and innovative teacher, creating new courses and learning structures. Her ability to engage students in a meaningful way with difficult concepts is a special gift.

“More importantly to me, she has encouraged and supported her students with a variety of opportunities that address different learning styles and needs,” Cogswell said, adding that she shows “that special combination of energy, enthusiasm and talent that demonstrate teaching at its best.”

Top image: Amy Palmer and (background) a hippocampal neuron expressing a zinc FRET sensor (Image by Lynn Sanford of the Palmer Lab)

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Amy Palmer, professor of biochemistry, recognized for revamping classroom experiences, championing diversity and striving to connect with students ‘beyond the course curriculum.’

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Not just the powerhouse of a cell

Anonymous — Thu, 19 Oct 2023 18:23:48 +0000

Not just the powerhouse of a cell Anonymous (not verified) Thu, 10/19/2023 - 12:23

Rachel Sauer

Newly published CU Boulder research reveals previously unknown qualities of a gene vital to a cell’s mitochondrial structure and function

A key takeaway from first-year biology is that mitochondria are the powerhouses of cells—it’s the thing most people know about them.

However, mitochondria perform a large array of functions for cells beyond generating the chemical energy that powers a cell’s biochemical reactions. They play a role calcium signaling and storage, signaling between cells and cell death. And through these various and vital mitochondrial functions, a master regulator is the OPA1 gene.

For a long time, researchers have known that OPA1 plays a crucial role in mitochondria. For example, OPA1 helps maintain the architecture of the mitochondria’s inner membrane. Without that maintenance, a protein, cytochrome c, can leak into the cell and trigger cell death at the wrong time.

While researchers have long known that OPA1 is vital to mitochondria and mitochondrial membranes in human cells, not much has been known about how OPA1 does its work. But research recently published in the journal Nature sheds new light on how OPA1 helps reshape mitochondrial membranes and how that translates to cellular health.

Halil Aydin, a CU Boulder assistant professor of biochemistry, led research that discovered surprising plasticity in the vital OPA1 gene.

“We’ve known for a long time that this gene exists, we know that it’s important in a variety of diseases, including cardiovascular disease, cancer, neurodegenerative disease,” says principal investigator Halil Aydin, a University of Colorado Boulder assistant professor of biochemistry. “What we didn’t know is how it functions. Our goal is to understand how it works and then in the future use that as a blueprint for developing therapeutic strategies or drugs.”

Unexpected plasticity

Aydin and his research group first separated OPA1 from cells and studied it in vitro to understand its atomic structure, which was no easy feat. When OPA1 is remodeling mitochondrial membranes in the cell, that process happens extremely fast, “we’re talking at the microsecond level,” Aydin says. “This was always confusing to me as a biologist, how it can happen so fast.”

One of the research group's biggest discoveries in studying OPA1 outside the cell was its plasticity and flexibility. Aydin says he had not been expecting to see that degree of plasticity, and while it went a long way toward explaining how OPA1 is so dynamic, it makes getting a clear photo very difficult.

The researchers used an electron microscope to study OPA1, “but imagine taking a picture with your phone,” Aydin says. “You move it even a little, something in the background moves even a tiny bit, and the picture is blurry. So, it was tough for us to find the conditions where we could just lock in on OPA1 and see it clearly. We were shocked by how dynamic and flexible it is.”

With a better understanding of OPA1’s atomic structure, Aydin and his research colleagues were better able to study it at work in mitochondrial membranes. They saw that through a particular lipid-binding process in mitochondrial membranes, OPA1 can help shape and reshape the mitochondria.

“Mitochondria are shaped like a tubule,” Aydin says. “If you think about them like a balloon animal, OPA1 changes the chape of the balloon depending on cellular needs or energy demands. OPA1 is like the person making the balloon animals.”

Aydin and his research group are currently collaborating with researchers at Vanderbilt University to directly study OPA1 activity in stem cell-derived neurons. Via molecular manipulation, they are studying how changes in OPA1’s activity affect essential cellular functions.

A clearer path

A broader aim of the newly published and ongoing research is to understand how molecular observations in the lab translate to cellular health, Aydin says. There are more than 400 disease variants that affect the OPA1 protein, and by determining its molecular architecture “we can better map all these disease mutations and understand how they affect protein functions,” Aydin says. “In the case of the neurons, that can lead to a decrease in neuronal health and cause optic neuropathies and other neurodegenerative disorders.”

For example, autosomal dominant optic atrophy, a hereditary disorder that can lead to progressive loss of vision or childhood blindness, is caused by mutations in the OPA1 gene. A goal of gene therapies in the future will be targeting and correcting this mutation, Aydin says.

“In science, we call this the bottom-up approach,” he says. “We start by looking at a single molecule, then the organelle, then the cell, then tissue, then systems. The power of this is that once we understand something at the atomic level, that translation gets clearer at each step that follows. So, as we learn more about how OPA1 functions, the path to better drugs and therapeutics becomes clearer.”

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Newly published CU Boulder research reveals previously unknown qualities of a gene vital to a cell’s mitochondrial structure and function.

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Studying the surprising similarities between humans and bacteria

Anonymous — Fri, 13 Oct 2023 22:29:57 +0000

Studying the surprising similarities between humans and bacteria Anonymous (not verified) Fri, 10/13/2023 - 16:29

Rachel Sauer

CU Boulder researcher Aaron Whiteley is recognized by the American Society for Microbiology for his work exploring bacterial immune responses and how it translates to the human immune system

A University of Colorado Boulder researcher has been recognized with the 2024 American Society for Microbiology Award for Early Career Basic Research for his work exploring how bacterial immune systems recognize and respond to phage infection.

Aaron Whiteley, an assistant professor of biochemistry, was honored for his research finding that bacterial and human immune systems are highly related and share a common ancestor. He and his research colleagues in the Whiteley Lab study what bacterial immune response can indicate about host-pathogen interactions and the mechanisms of signaling in human cells.

By focusing on specific signaling pathways in bacteria and human cells, particularly the cGAS-STING pathway, Whiteley hopes to better understand the role they play in resistance to infectious disease and cancer. Better understanding can inform better, more-targeted therapeutics.

Common ancestors

Whiteley’s research began with an interest in host-pathogen interactions, “how viruses and bacteria make humans sick,” he says. “And more generally, I’ve always been interested in aspects of microbiology, how bacterial organisms go about their daily life.

CU Boulder researcher Aaron Whiteley recently was recognized by the American Society for Microbiology with the 2024 Award for Early Career Basic Research.

During his post-doctoral studies, he worked on research studying how bacteria defend themselves against phages, which are viruses that infect and replicate only in bacterial cells and are the most abundant organisms in the biosphere. He was electrified by the discovery of an enzyme that not only defends against phages, but whose homologue—or a gene inherited in two species from a common ancestry—defended human cells against viruses.

That led him to the study of phages and common ancestors that both human cells and bacteria share.

“We tend to think of the human immune system as this intricate system of genes that maybe animals invented in isolation,” Whiteley says. “What our and other research has shown is that probably over a billion years ago, bacteria and unicellular animals were interacting. Maybe the animal was eating the bacteria, because somehow the genes in the bacteria got into the germ line of that animal.

“If the gene was anti-viral in bacteria, it was anti-viral in the animal cell, which is probably why we kept it. It was stolen from bacteria and now used to detect viruses that would make animals sick. Mice have these genes, we have these genes, bacteria have these genes. Our contention is that if we can figure out how this immune response works in bacteria, we can better understand how it works in human cells.”

Studying immune signaling

Whiteley and his research group focus on two major families of immune signaling or innate immune genes: cGAS, which plays a critical role in immunity by detecting foreign DNA, and NLR-related proteins.

“NLRs in human cells detect all sorts of pathogens, and we’ve found them in bacteria, which has been really cool,” Whiteley says. “We’ve been trying to understand how they work; the main emphasis is how they sense the virus. How does the cell see to know that there’s a virus inside of it?

“That’s a really tough question biochemically for a bacterium to figure out. Viruses are so good at stripping themselves down to just their genome, so this is a fascinating problem that viruses and hosts have been arguing over: Viruses are trying to become the most minimal and most inconspicuous, and the host is looking for any molecular signal to recognize them.”

Every time researchers think a host has outsmarted the virus, Whiteley says, they discover that the virus has made another protein that inhibits the host’s detection system. “Viruses always seem to have the upper hand, yet we’re still here,” Whiteley says. “In both our immune system and the bacterial immune system, there isn’t just one pathway; there are hundreds.”

Whiteley notes that while the human immune system is essentially the same between individuals, there may be few or no similarities in immune systems between two bacteria plucked from the wild. For example, two E. coli cells may have dozens of different pathways for detecting the virus and no similarities between the two cells.

“So, the virus now has to keep up with all of those different pathways in each individual cell,” Whiteley says. “E. coli have figured out how to decentralize this knowledge and spread it out all over, which probably contributes to why any host still exists.”

Better at treating disease

By understanding the ancestors of these signaling proteins present in human cells and originating in bacterial ones, Whiteley and his lab group aim to understand fundamental qualities of the human immune system.

We haven’t actually diversified that much from our bacterial roots. The protein structures are the same, so if we can understand what these proteins do in bacteria then it may be much easier to apply that understanding to humans.”

“We haven’t actually diversified that much from our bacterial roots,” he says. “The protein structures are the same, so if we can understand what these proteins do in bacteria then it may be much easier to apply that understanding to humans. If we can figure out how bacteria turn them on, that might be a good understanding that can inform the next RNA vaccine.”

A mutated version of human NLRs is associated with ulcerative colitis and inflammatory bowel disease, so understanding how the NLRs are signaling generally may lead to better treatments. There also is a potential to develop better caner immunotherapy drugs and treatments for autoimmune disease through understanding the cGAS-STING pathway.

“Anti-phage proteins seem to have great applications in biotech and I’m excited to continue working on that,” Whiteley says. “We’ve developed a biosensor for the human cGAS pathway and maybe down the road that will help us understand whether a cancer patient is going to respond to a particular treatment.

“If we can better understand how to turn more of a person’s immune system on or make sure they’re taking the right drug ahead of that activation, I think we’re going to be much better at treating disease.”

Top image: phages on a bacteria cell (source: Eye of Science/Science Source)

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CU Boulder researcher Aaron Whiteley is recognized by the American Society for Microbiology for his work exploring bacterial immune responses and how it translates to the human immune system.

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International award recognizes researcher’s contributions to life science

Anonymous — Thu, 14 Sep 2023 15:17:55 +0000

International award recognizes researcher’s contributions to life science Anonymous (not verified) Thu, 09/14/2023 - 09:17

CU Boulder distinguished professor Karolin Luger is awarded the 2023 World Laureates Association Prize in Life Sciences or Medicine

University of Colorado Boulder researcher Karolin Luger, a distinguished professor of biochemistry and Jennie Smoly Caruthers Endowed Chair of Biochemistry, has been awarded the 2023 World Laureates Association Prize in Life Science or Medicine.

The award, announced Thursday morning in Shanghai, China, recognizes Luger’s deep body of research “elucidating the structure of the nucleosome at the atomic level, providing the basis for understanding chromatin, gene regulation and epigenetics,” the award citation notes.

The World Laureates Association (WLA) Prize is an international science prize established in 2021 that recognizes researchers and technologists worldwide for their contributions to science. It aims to “support global science and technology advancement, address the challenges to humanity and promote society's long-term progress,” according to the WLA.

The WLA Prize is awarded in two categories: computer science or mathematics and life science or medicine. The winners in each category share approximately $1.38 million as part of the award.

CU Boulder distinguished professor Karolin Luger received the 2023 World Laureates Association Prize in Life Science or Medicine Thursday.

Luger is joined in the WLA Prize in Life Science or Mathematics by Daniela Rhodes, emeritus group leader at the MRC Laboratory of Molecular Biology at Cambridge University, and Timothy J. Richmond, professor emeritus of crystallography of biological macromolecules at ETH Zurich.

Luger, Richmond and Rhodes partnered on groundbreaking research published in 1997 that “revealed details of the nucleosome structure that have guided subsequent studies on chromatin-binding proteins, histone-modifying enzymes and nucleosome positioning and remodeling and their control of transcription regulation and DNA replication,” the WLA notes. The three laureates "have left an indelible mark on the history of our understanding of chromosome structure" through their more than two decades of research.

Luger and her colleagues in the Luger Lab focus much of their current research on the structural and mechanistic biology of genome organization in all domains of life. A significant goal is to understand the fundamental impact of chromatin architecture on genome-related processes such as gene transcription, DNA replication and DNA repair in eukaryotes, or cells in which the genetic material of DNA is contained within a nucleus in the form of chromosomes. They also study chromatin organization in non-eukaryotic organisms such a viruses, archaea and bacteria, to elucidate the evolutionary origins of the nucleosome.

The lab also studies a protein that serves as a first responder to DNA damage, by recruiting the complicated machinery to prevent dangerous, disease-causing mutation. An aim of this research is to design better drugs for treating cancer through comprehensive investigations of its structure and mechanism.

The WLA Prize is a meaningful recognition of this research. “Just like the DNA double helix which it organizes, the nucleosome is almost transcendent in its beauty, and it provides so much insight into genome organization,” Luger says. “Images of the structure are found on the cover of textbooks, in museums and they have inspired works of art. It took a lot of effort and grit not just from the three of us, but by many of our coworkers, to make it reveal its secrets. I am thrilled and honored to share this prize with Tim and Daniela, but in my mind the real winner is the nucleosome.”

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CU Boulder distinguished professor Karolin Luger is awarded the 2023 World Laureates Association Prize in Life Sciences or Medicine.

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The right zinc levels are key to human health, researchers find

Anonymous — Mon, 24 Jul 2023 17:39:30 +0000

The right zinc levels are key to human health, researchers find Anonymous (not verified) Mon, 07/24/2023 - 11:39

Rachel Sauer

Using innovative fluorescent sensors and computational modeling, CU Boulder biochemistry researcher Amy Palmer tracked naturally cycling cells to better understand an essential micronutrient

Zinc is one of those micronutrients that many people know they need but are otherwise a little vague on the particulars.

Unlike, say, calcium, which most people know can be gained from a glass of milk, or the potassium found in a banana, sources of zinc sometimes aren’t as well-known.

The unknowns about zinc further extend to how it works in the body. While research has demonstrated that zinc is essential for a host of vital functions—from cell growth and proliferation to DNA creation, immune system support, building proteins and many others—not much has been known about how zinc does its work. In fact, a lot of what scientists know about how zinc functions in the body, especially its role in growth, has been learned by studying its absence in cases of zinc deficiency.

Amy Palmer, professor of biochemistry, developed innovative technology to measure zinc in naturally cycling cells over 60 hours.

However, newly published research led by Amy Palmer, a professor in the University of Colorado Boulder Department of Biochemistry, sheds new light—fluorescent light, in fact—on zinc’s role in cell growth. The research shows that when zinc levels are too low or too high, all cell proliferation stops until zinc levels come back into an acceptable range. It also revealed a phenomenon the researchers called a “zinc pulse"—right after a cell divides, it experiences a transient increase in zinc that comes back down after about an hour.

Palmer and her research colleagues, post-doctoral research associate Ananya Rakshit and graduate student Samuel Holtzen, were able to arrive at this new understanding of zinc’s vital role by using genetically encoded fluorescent sensors that change color and give off light when zinc binds to them.

“For the field, these fluorescent sensors were a big breakthrough because they allowed us to measure and quantify zinc in individual cells over many hours,” Palmer explains. “We can watch the zinc as the cell gets ready to divide, as it divides and as the two daughter cells go through the same process.

“We need to understand at the cellular level why is it that zinc is required, where is it required, how much is required. One missing piece of the puzzle, particularly when we think of zinc supplementation, is understanding and knowing when cells need zinc and how much they actually need.”

Using fluorescence

Palmer, who is internationally recognized for her work in developing the fluorescent sensors that detect metals in cells without disrupting cell function, and her research colleagues used a bit of biochemistry and a bit of engineering to create a sensor that will bind to zinc and only zinc.

“These fluorescent reporters are less perturbing to cells, letting them naturally cycle, and they’re really the wave of the future for this field of research,” Palmer says. “My colleague Sabrina Spencer really pioneered the approach of studying naturally cycling cells, and we learned a lot from her and her lab. Our angle was to take these fluorescent reporters and create some specifically for zinc.”

When Palmer initiated her lab at CU, she and her colleagues began developing these fluorescent sensors, building on post-doctoral research that Palmer completed with her advisor, Roger Tsien. Tsien won the Nobel Prize in Chemistry for discovering and developing the green fluorescent protein, which he and other scientists used to track when and where certain genes are expressed in cells.

“What’s really fun about these fluorescent sensors is they’re made out of proteins that are genetically encoded,” Palmer says. “They have a DNA sequence, and that one piece of DNA encodes a protein that will bind to zinc.

“This color switch when it binds to zinc specifically, this was a big breakthrough. It’s easy to get a very small response, but it’s harder to get a really big, robust response that can be used to track cells over 60 hours. We went through a lot of iterative optimization of our tools to get them to work the way we want.”

The effort paid off, though, because a lot of previous research added chemicals to cells to stop them from dividing or removed their growth serum—a process that could also remove zinc. Then, removing the chemical or adding the growth serum reinitiated cell division, aligning the cells so that they were all doing the same thing at the same time. That scenario, however, is not representative of what happens in a human body.

By introducing the fluorescent reporters to cells, Palmer and her colleagues could not only measure zinc levels, but also track each individual cell over 60 hours. Working with naturally cycling cells allowed the cells do their normal business in real time. Then, the researchers computationally figured out what state each cell was in and how much zinc it contained at each point during that time.

Implications for nutrition and disease

Palmer’s research was not only important because of the innovative tools being developed and used to study the cell cycle, but because zinc’s essentiality is not widely known yet the impacts of zinc deficiency can be significant. About 17% of the world’s population is zinc deficient and zinc deficiency represents a public health crisis in some parts of the world.

Palmer and her co-researchers found that a cell experiences a “zinc pulse" right after it divides and has a transient increase in zinc that comes back down after about an hour.

Severe zinc deficiency can result in slowing or cessation of growth and development, delayed sexual maturation, impaired immune function and wound healing and many others. However, scientists are just now beginning to understand when cells need zinc and how much of it they need.

By using fluorescent sensors to track zinc uptake in individual cells over 60 hours, Palmer and her co-researchers were able to discover the zinc pulse that occurs right after a cell divides.

“We don’t yet know exactly why that happens, but we speculate that the two new daughter cells need to bring in a lot of zinc to set up growth in the individual cell,” Palmer says. “If they don’t have that pulse then they can’t keep going and they have to pause.”

The researchers also saw that zinc levels need to be just right—if they’re too high or too low then cell function pauses until zinc levels return to normal. During that pause, they observed that cells struggled to make DNA.

Building on the results of the recently published study, undergraduate researchers in Palmer’s lab are studying the very high levels of zinc often found in breast cancer cells and why those cells don’t pause in response to high zinc levels the way healthy cells would. It’s almost as though cells have a safety switch that cancer is somehow able to bypass, Palmer says.

Digging deeper into when and why cells need zinc and how much of it may “have implications for understanding human nutrition at the whole-organism level, implications for understanding zinc dysregulation or dysfunction in disease,” Palmer says. “We’re really working to understand that set point and that fundamental mechanism that each cell has where it senses its zinc status and how, within a certain range, it can regulate how much zinc it has.

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Using innovative fluorescent sensors and computational modeling, CU Boulder biochemistry researcher Amy Palmer tracked naturally cycling cells to better understand an essential micronutrient.

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CU Boulder’s Aaron Whiteley named a Pew Scholar

Anonymous — Tue, 13 Jun 2023 17:57:08 +0000

CU Boulder’s Aaron Whiteley named a Pew Scholar Anonymous (not verified) Tue, 06/13/2023 - 11:57

The biochemistry assistant professor is investigating how inflammatory proteins called NLRs establish the first line of defense against viral infection in bacteria and humans

Aaron Whiteley, an assistant professor in the Department of Biochemistry at the University of Colorado Boulder, has been selected to join the Pew Scholars Program in the Biomedical Sciences, the Pew Charitable Trusts announced today.

“I am truly thrilled to be named a Pew Scholar,” said Whiteley. “Support from this grant will help my lab pursue high-risk/high-reward research on how the immune system recognizes pathogens. I hope one day our findings can inform design of the next generation of vaccines and antiviral treatments.”

Aaron Whiteley, an assistant professor in the Department of Biochemistry at CU Boulder, was recently selected to join the Pew Scholars Program in the Biomedical Sciences. Whiteley’s recent research has identified unexpected similarities between how bacteria and human cells fight off viruses.

This award follows a recent publication from the Whiteley lab in the journal Cell that identified unexpected similarities between how bacteria and human cells fight off viruses. The article reveals that a part of the human immune system, called “NLRs,” actually originated from bacteria.

“Like studying a fossil, understanding bacterial ancestors of our NLRs will help us understand the human immune systems,” Whiteley said.

He added, “One of the most impactful aspects of being a Biomedical Scholar is connection to the fantastic network of Pew-supported scientists from across the country. This award is career milestone—I am grateful for the recognition and opportunity.”

Whiteley is one of 22 early career scientists who will receive four years of funding to spearhead innovative studies exploring human health and medicine.

This award is career milestone—I am grateful for the recognition and opportunity.”

The 2023 class—all early career, junior faculty—joins a rich legacy of more than 1,000 scientists who have received awards from Pew since 1985. Current scholars have opportunities to meet annually with fellow Pew-funded scientists to exchange ideas and forge connections across a wide variety of disciplines.

“From vaccine development to treatments for complex diseases, biomedical research is foundational to solving some of the world’s greatest challenges,” said Susan K. Urahn, Pew’s president and CEO. “Pew is thrilled to welcome this new class of researchers and support their efforts to advance scientific knowledge and improve human health.”

Scholars were chosen from 188 applicants nominated by leading academic institutions and researchers throughout the United States. This year’s class includes scientists who are studying how external and internal factors affect the gut microbe, what causes HIV to re-emerge when treatment is halted and how living an urban lifestyle affects long-term health.

“This new class of scholars embodies the creativity and curiosity that is key to science discovery,” said Craig C. Mello, a 1995 Pew scholar, 2006 Nobel Laureate in physiology or medicine and chair of the national advisory of committee for the scholars’ program.

“With support from Pew and its network of colleges and advisors, I am confident this group will do great things to advance biomedical science.”

The biochemistry assistant professor is investigating how inflammatory proteins called NLRs establish the first line of defense against viral infection in bacteria and humans.

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Three CU Boulder profs win Boettcher Foundation awards

Anonymous — Mon, 12 Jun 2023 23:12:26 +0000

Three CU Boulder profs win Boettcher Foundation awards Anonymous (not verified) Mon, 06/12/2023 - 17:12

The awards are part of $1.88 million in 2023 biomedical research grant funding for Colorado researchers

Three University of Colorado Boulder assistant professors have been named 2023 Boettcher Investigators, each earning $235,000 in grant funding to support up to three years of biomedical research. The 13-year-old program invests in leading Colorado researchers during the early stages of their careers, providing support to fund their independent scientific research.

Nuris Figueroa Morales studies the complex interactions between microorganisms and their environment.

The three CU Boulder award winners and their fields of study are:

Nuris Figueroa, assistant professor, physics; studying the mechanics of mucus organization and transport;
Halil Aydin, assistant professor, biochemistry; investigating cellular and molecular mechanisms of mitochondrial form and function in human health and disease; and
Nick Bottenus, assistant professor, biomedical, mechanics of materials, and robotics and systems design in the College of Engineering and Applied Science; studying binding kinetics of targeted microbubble agents.

Funding for the awards is made possible in part by the Webb-Waring Biomedical Research Awards program, which is administered by the Boettcher Foundation.

“It’s an honor to be acknowledged by a distinguished organization,” Aydin said of the Boettcher Foundation. “The Boettcher Foundation Webb-Waring Biomedical Research Award will grant our laboratory the opportunity to develop novel approaches and push the boundaries of high-resolution imaging and structural cell biology to advance our understanding of how cellular machines function normally, and how they are corrupted by disease. An integrative understanding of how protein machines function has implications for targeting cardiovascular diseases, metabolic disorders, cancers, aging and a wide range of neurodegenerative diseases.”

Halil Aydin is an expert in membrane biology, cell signaling, proteins and enzymology, molecular biophysics, structural biology, and electron cryo-microscopy (cryoEM).

Figueroa also expressed thanks to the Boettcher Webb-Waring Biomedical Research Program and for what the funding will mean for her research team’s work.

“With this research grant, my team and I will have the means to investigate mechanical properties of lung mucus, how it flows, and how bacteria navigate in it,” she said. “Our research will look at the biophysics of lung-obstructive diseases using new quantitative and interdisciplinary tools, to further understand causes and consequences of failed mucus clearance and hopefully device solutions.”

Bottenus said, “Being named a Boettcher Investigator is an amazing career milestone. I’m grateful to become a part of a rich community of biomedical researchers throughout Colorado. This award will allow my group to grow in new directions, applying our acoustics and signal processing techniques to more fundamental biological investigations. I hope that our work will translate to improved diagnostic imaging, personalized medicine, and accessible health care technologies as we pursue new approaches to molecular imaging.”

Assistant Professor Nick Bottenus' research is focused on developing system-level solutions to problems in diagnostic ultrasound imaging.

The awards given to the three CU Boulder assistant professors are part of a larger pot of $1.88 million grant funding awarded to eight individuals from four of Colorado’s research institutions: CU Boulder, University of Colorado Anschutz Medical Campus,Colorado State University and National Jewish Health.

“We are thrilled to support our 2023 Boettcher Investigators, and as proud investors in their work, we are confident that these exceptional researchers will continue to push the boundaries of discovery and medical breakthrough,” said Katie Kramer, president and CEO of the Boettcher Foundation. “Their innovative research holds the promise of transformational impact that will drive progress in health care and make a meaningful difference in the lives of Coloradans.”

Since its inception in 2010, the Webb-Waring Biomedical Research Awards program has advanced the work of 98 Boettcher Investigators with more than $20 million in grant funds. The researchers have attracted more than $150 million in additional independent research funding from federal, state and private sources.

“Colorado BioScience Association applauds Boettcher Foundation’s support of Colorado’s most dynamic and promising researchers,” said Elyse Blazevich, president and CEO of the Colorado BioScience Association.

“The Webb-Waring Biomedical Awards program invests in Colorado researchers at a pivotal time in their careers and encourages them to deepen their roots in Colorado as they contribute to the leading-edge health innovations coming from our state.”

The awards are part of $1.88 million in 2023 biomedical research grant funding for Colorado researchers.

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Three scientists win support for high-risk, high-reward research

Anonymous — Tue, 04 Oct 2022 14:41:14 +0000

Three scientists win support for high-risk, high-reward research Anonymous (not verified) Tue, 10/04/2022 - 08:41

National Institutes of Health funds CU Boulder researchers’ work on mental illnesses, HIV vaccines and improved cancer treatments

Three scientists at the University of Colorado Boulder have won prestigious, High-Risk, High-Reward Research Program awards, the National Institutes of Health (NIH) announced today.

The awards to Lisa Hiura, Sara Sawyer and Aaron Whiteley are among 103 grants nationwide, totaling more than $200 million over five years. Hiura, Sawyer and Whiteley won support for their respective research probing mental illnesses that appear in adolescence, facilitating better and faster development of HIV vaccines, and understanding the connection between the gut microbiome and the efficacy of cancer treatments.

“The science advanced by these researchers is poised to blaze new paths of discovery in human health,” said Lawrence A. Tabak, DDS, PhD, the director of NIH.

“This unique cohort of scientists will transform what is known in the biological and behavioral world. We are privileged to support this innovative science.”

At the top of the page: Sara Sawyer. Above: Lisa Hiura.

Hiura, a postdoctoral fellow in molecular biology, has won the Director’s Early Independence Award, which supports “outstanding junior scientists with the intellect, scientific creativity, drive and maturity bypass the traditional postdoctoral training period to launch independent research careers.” The five-year grant carries $1.25 million in funding.

Hiura plans to study a mechanism that plays a crucial role in people’s ability to form close bonds with loved ones. When that mechanism, called the mesolimbic dopamine system, functions atypically, neuropsychiatric diseases can arise during adolescence, Hiura notes.

Social experiences play a crucial role in brain development, says Hiura, adding that “the ways in which changing adolescent reward circuits are shaped by early social interactions to facilitate adult bonding remains unknown.”

Hiura plans to “leverage the use of the socially monogamous prairie vole system to discover the activational, functional and transcriptional features of dopaminergic reward circuit development, furthering our understanding of the pathophysiology of diseases that involve impaired social bonding behaviors.”

Hiura said she was honored to be selected, adding: “It is an incredible opportunity to immediately begin pursuing my research questions on the developmental origins of social bonding. Recent advances in our ability to observe and probe brain function makes this an especially exciting time to be in social neuroscience. With this grant, my lab will be able to tap into the molecular processes that transform our early experiences into the neural foundations of our psychosocial health and wellbeing.”

Sawyer, professor of molecular, cellular and developmental biology, has won a Pioneer Award, which supports scientists with “outstanding records of creativity pursuing new research directions to develop pioneering approaches to major challenges in biomedical, social science and behavioral research.” It is a five-year, $3.5 million grant.

Sawyer and her team will be developing a new model organism that will facilitate better and faster development of HIV vaccines. Sawyer has been working on this breakthrough for a decade and says, “Just like young people today, I grew up in the era of an emerging pandemic. I remember thinking as a teenager that I wanted to help in the fight against HIV/AIDS, and that determination has only intensified with time.”

HIV has killed 36 million people, and another 37 million people are living with chronic infection. Even today, almost 2,000 people per day die of HIV/AIDS globally.

Aaron Whiteley

Whiteley, assistant professor of biochemistry, has won a New Innovator Award, which is reserved for “exceptionally creative early career scientists proposing innovative, high-impact projects.” It is a $1.5 million, five-year grant.

Whiteley’s research aims to shed light on why variations in bacteria in the gut microbiome correspond to variations in cancer patients’ responsiveness to immunotherapy. The mechanism is not well understood.

Recent evidence suggests the cGAS-STING immune pathway, an immune system pathway that is a key mediator of inflammation from infection, cellular stress or tissue damage, also plays a crucial role in activating anticancer signaling, and Whiteley’s group has found that gut-associated bacteria produce signaling molecules that activate with this pathway.

He adds: “Funding from the New Innovator Award provides critical support for our ambitious project. We hope that by understanding how bacteria in the microbiome manipulate cGAS-STING signaling, we will enable future development of better anticancer therapeutic agents."

The NIH Common Fund’s High-Risk, High-Reward Research program aims to accelerate the pace of biomedical, behavioral and social science discoveries by supporting exceptionally creative scientists conducting highly innovative research.

The program seeks to identify scientists with high-impact ideas that may be risky or at a stage too early to fare well in the traditional peer review process. The program encourages creative, outside-the-box thinkers to pursue exciting and innovative ideas in any area of biomedical, behavioral or social science within the NIH mission.

The NIH Common Fund encourages collaboration and supports a series of exceptionally high-impact, trans-NIH programs.

The NIH, the nation's medical research agency, includes 27 Institutes and centers and is a component of the U.S. Department of Health and Human Services.

The NIH is the primary federal agency conducting and supporting basic, clinical and translational medical research, and is investigating the causes, treatments and cures for both common and rare diseases.

National Institutes of Health funds CU Boulder researchers’ work on mental illnesses, HIV vaccines and improved cancer treatments.

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Major gift to enhance diversity of life-science researchers

Anonymous — Fri, 17 Jun 2022 21:56:40 +0000

Major gift to enhance diversity of life-science researchers Anonymous (not verified) Fri, 06/17/2022 - 15:56

With support from the Shurl and Kay Curci Foundation, six life-science scholars gain support during their first two years of PhD work, beginning this fall

Six life science scholars will embark on their PhD studies and contribute their unique cultural experiences to the University of Colorado Boulder campus this fall through a nearly $1.9 million gift to the university from the Shurl and Kay Curci Foundation, the foundation has announced.

The foundation is a California-based organization whose mission is “to support science-based research striving for the advancement of a healthy and sustainable future for humans.”

CU Boulder’s incoming Curci Scholars, five of whom are women and five of whom are international students, will enter graduate programs in molecular, cellular and developmental biology, biochemistry, psychology and neuroscience or integrative physiology.

Six incoming life-science scholars are, top row, from left: Angie Liu, Emily Prevost, Emily Yeo; bottom row: Hope Townsend, Joshiah Peters, Sophie Breunig.

The gift will ultimately support 12 graduate students through the first two years of their PhD education “with the hope of increasing the percentages of gender diversity and international students at the university pursuing a PhD in the life sciences,” according to the gift agreement.

Through the gift, the university aims to award two-thirds of the scholarships to international students and half to increase gender diversity in the life sciences. The second cohort of six Curci Scholars will be awarded beginning in 2023.

“We are deeply grateful for the generosity and foresight of the Curci Foundation. It is an honor and a joy to partner with them to significantly expand the opportunities for women and international students to earn a doctoral degree in life sciences at a top-tier research institution,” said James W.C. White, acting dean of the College of Arts and Sciences.

“Our graduate research programs in the life sciences are excellent and perform critically important work that makes life better for all of us. The Curci Scholarship will enhance the diversity, international prominence and human impact of these programs.”

Lee Niswander, professor and chair of the Department of Molecular, Cellular and Developmental Biology, concurred, saying that the university’s life-science departments are “thrilled” to partner with the Curci Foundation to enrich and expand the university’s graduate programs.

She added: “The Curci scholarship has already fundamentally enhanced our recruitment of exceptional international and gender diverse scholars, and our world-known research laboratories will provide rich experiences for these scholars in cutting-edge life science research. We are extremely grateful to the Curci Foundation for their generous support.”

The foundation’s gift to CU Boulder is one of six made to elite institutions in the United States, the others being the University of Utah, the University of California, Berkeley, UC San Diego, UC San Francisco and the University of Washington.

Header image courtesy of Institute of Cognitive Science’s Intermountain Neuroimaging Consortium

With support from the Shurl and Kay Curci Foundation, six life-science scholars gain support during their first two years of PhD work, beginning this fall.

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