Postdoctoral Research

A key ‘kill switch’ in a gene-regulating protein group

Anonymous — Mon, 09 Sep 2019 06:00:00 +0000

A key ‘kill switch’ in a gene-regulating protein group Anonymous (not verified) Mon, 09/09/2019 - 00:00

Trent Knoss

��񱦵� and Howard Hughes Medical Institute (HHMI) biochemists have revealed a key regulatory process in a gene-suppressing protein group that could hold future applications for drug discovery and clinical treatment of diseases, including cancer.

The new research, recently published in the journal Genes & Development, centered on a protein group known as Polycomb Repressive Complex 2 (PRC2), which acts as a gatekeeper for gene expression as cells differentiate and tissues develop.

“PRC2 plays a critical role in stem cell differentiation to make sure that irrelevant genes are switched off,” said Yicheng Long, an HHMI post-doctoral fellow and a co-author of the study. “If you have a muscle cell, for example, PRC2 shuts off genes that are specific to the brain.”

When that regulation goes awry, however, abnormal PRC2 activation is suspected to play a role in the development of diseases such as cardiac hypertrophy, Huntington’s Disease and multiple types of cancer.

Researchers from HHMI and ��񱦵�’s Department of Biochemistry began by re-examining exactly how PRC2 achieves methylation, a complex epigenetic process by which proteins modify the structure of regions of chromosomes.

While examining the activity of human PRC2, the scientists began to notice a “mystery band” appearing in the data. As PRC2 was previously known to modify an important histone protein that is a fundamental unit of human chromosome, the scientists indeed observed this modification in vitro. Surprisingly, the scientists noticed another modification event indicated by this “mystery band.” Although other scientists had seen this band before, nobody could understand how and why it was happening.

“This unexpected band caught our attention and we suspect that this could represent a novel activity and function of PRC2,” said Xueyin Wang, one of the two co-first authors of the study and a then-��񱦵� graduate student now with A2 Biotherapeutics Inc. in California.

Further investigation revealed that this “mystery band” is a self-modification event (named “automethylation”) which have important physiological functions. Using mass spectrometry, it became apparent that PRC2 automethylates three lysines of a flexible, evolutionarily conserved loop. The loop essentially holds the key to its own lock within its own structure and remains poised in an inhibited state. Automethylation of the three lysines unlocks this loop from PRC2’s catalytic center and thus relieves PRC2 from the poised state.

“The interesting question is why nature would devise such a mechanism,” Long said.

The researchers hypothesize that with abundant level of PRC2 in stem cell, the flexible loop ensures that most of it stays inactive until needed, like a fire sprinkler that stays closed during normal operations, only opening when a fire needs to be extinguished. If that sprinkler ever malfunctions and remains open (as in a cancerous mutation), biochemists can now foresee a means of re-closing it to prevent unwanted flooding.

“Others have found the way to activate PRC2,” Long said. “We found a key to turning it off.”

“I expect that many other examples of automethylation will be found,” said Nobel Laureate and Distinguished Professor Thomas Cech, the senior author of the study and an HHMI Investigator. “Many enzymes that regulate our genes do so by adding methyl groups to their target proteins. So they’re also primed to add methyl groups to themselves, allowing them to self-regulate their own activity.”

With greater knowledge of PRC2’s form and function, the research could one day lead to more specific clinical focus on inhibiting activations associated with tumor formation and other known disease pathways.

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Yuanyuan Xie awarded National Cancer Center fellowship to explore the pathological role of transposons

Anonymous — Wed, 12 Jun 2019 14:56:18 +0000

Yuanyuan Xie awarded National Cancer Center fellowship to explore the pathological role of transposons Anonymous (not verified) Wed, 06/12/2019 - 08:56

Lindsay Diamond

Nearly all species’ genomes are littered with millions of genetic sequences called transposons, which are virus-like parasitic elements that can replicate and spread within host genomes. Collectively, transposon-derived sequences constitute about 50 percent of the human genome sequence, and are believed to have - over tens of millions of years - played a critical role in our evolution. Transposons are increasingly recognized to have influenced human biology and adaptation, particularly in the realms of development and immunity. Transposons may also contribute to disease.

Yuanyuan Xie, a postdoctoral researcher in the Chuong Lab, was recently awarded a National Cancer Center Postdoctoral Fellowship to explore the pathological role of transposon-derived sequences known as retrocopies in colorectal cancer.

For the cell to create proteins, the DNA sequence of a gene is transcribed into RNA, which is then normally translated into a protein. However, cellular RNAs are occasionally reverse-transcribed back to DNA and inserted into a different location in the genome, forming a type of gene duplication known as a retrocopy. Retrocopies originate from the activity of retrotransposons, which replicate by reverse transcribing their own RNA into host DNA, but occasionally capture cellular RNAs by accident. While over 8,000 retrocopies can be detected in the human genome, they are often assumed to be nonfunctional. Nevertheless, genomic studies have revealed that many retrocopies have transcribed RNAs or even translated proteins, often with distinct activities from their parental genes.

Repeat sequences can have deleterious effects in the genome and underlie several human disease conditions including Huntington’s disease, fragile X syndrome, several ataxias, and myotonic dystrophy. To protect against potential harm, all organisms have evolved genomic defenses to repress transposons through epigenetic manipulation. Yet, repression is inherently reversible, and inappropriate reactivation of transposons are common in many cancers. However, the specific cellular functions of retrocopies and whether they play a genome-wide role in cancer progression remain unknown.

Answering these questions is what drew Yuanyuan to the interdisciplinarity of Chuong Lab and the BioFrontiers Institute. “My previous experience was in cell signaling pathways and stem cell models, and I was interested in joining the Chuong Lab where I can learn computational genomics to study gene regulatory networks in evolution and disease,” says Xie.

Taking a break from the bench, Yuanyuan scoured The Cancer Genome Atlas (TCGA), a joint effort between the National Cancer Institute and the National Human Genome Research Institute that has characterized over 20,000 primary cancer and normal samples across a variety of different cancers, in search of candidates where there is increased expression of retrocopies, rather than parental genes, in primary tumors.

Now with the fellowship funding, Yuanyuan will head back to the bench to test his hypotheses. “Through activities like DNA and histone modification, these repetitive elements are derepressed in states like cancer and aging. The question remains whether this derepression is a consequence or a cause,” says Xie.

Looking forward, Yuanyuan plans to extend the analysis to a genome-wide CRISPR screen to identify novel protein-coding and non-coding retrocopies involved in tumorigenesis. Overall these experiments seek to uncover an understudied yet potentially extensive pathological role for retrocopies in colorectal cancers wherein the mechanism may be applied to other types of cancers. These studies may help pave the road for more precise cancer therapies that specifically target retrocopies.

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Flu researchers discover new mechanism for battling influenza

Anonymous — Thu, 02 Nov 2017 06:00:00 +0000

Flu researchers discover new mechanism for battling influenza Anonymous (not verified) Thu, 11/02/2017 - 00:00

Lisa Marshall

Just as flu season swings into full gear, researchers from the ��񱦵� and University of Texas at Austin have uncovered a previously unknown mechanism by which the human immune system tries to battle the influenza A virus. The discovery sheds new light on how the virus — which kills 12,000 to 56,000 people in the United States annually — often wins, and it could ultimately lead to new treatments.

“We’ve solved a mystery, revealing a new aspect of our innate immune system and what flu has to do to get around it,” says Nicholas Meyerson, a postdoctoral researcher in the BioFr ontiers Institute and lead author of a paper published in the Nov. 8 issue of Cell Host and Microbe.

The findings, several years in the making, could lead to a better understanding of how the seasonal flu virus, which typically originates in birds, makes its way to humans. They could also inform development of next-generation antivirals able to combat a broad spectrum of influenza strains, says co-senior author Robert Krug, a leading influenza researcher and professor at the University of Texas at Austin.

The paper focuses on two key molecular players in the story of influenza infection: a human protein called TRIM25, which was recently discovered to play an important role in the human immune response to flu infection; and a protein called NS1 present in all strains of the influenza A virus and shown to bind TRIM25 to keep it from doing its job.

“We were basically trying to find out what TRIM25 was doing that flu did not want it to be doing and the role NS1 was playing in blocking that function,” Krug said.

Through a series of laboratory tests, the team revealed two main findings:

TRIM25 acts earlier than previously believed, latching on to a critical and unique flu virus structure like a “molecular clamp” to keep the virus from replicating as soon as TRIM25 detects this unique structure.

NS1 produced by the flu virus can block this function of TRIM25, enabling flu to circumvent the immune response and cause infection.

Previous research had suggested that TRIM25 fought off flu by switching on what is known as the “interferon response” — a complex signaling pathway that arms cells through the body to fight off pathogens. But not all strains of influenza block this interferon signaling pathway, which led Meyerson to suspect another mechanism was at play in helping TRIM25 fight flu.

The paper reveals that TRIM25 is also a “restriction factor,” a special protein present in the fastest-acting arm of the immune system, before spreading infection occurs.

“Restriction factors lie in wait, and should a virus be detected in one of your cells, they have immediate destructive ability,” explains co-senior author Sara Sawyer, an associate professor of Molecular, Cellular and Developmental Biology (MCDB) at ��񱦵�.

Flu uses its NS1 protein to evade TRIM25’s early flu-fighting response, the researchers found.

To do the study, the researchers first infected transgenic cell lines loaded with nonhuman primate versions of TRIM25 with the human influenza A virus. They found that the cells fought off the virus far better than human versions of the TRIM25 protein.

“This told us that TRIM25 has the capacity to crush influenza, but that its human form was less active,” Meyerson said.

To find out how it crushes influenza, the researchers combined purified TRIM25 with purified viral ribonucleoproteins (vRNPs) — eight-piece protein chains that house the influenza genome — and used state-of-the-art electron microscopy to take pictures of what happened.They found that TRIM25 appears to swiftly recognize the unique structure of vRNPs and clamps down on them to keep them from replicating inside the cell.Other experiments confirmed that the NS1 protein in flu virus inhibits this function.

They also found that TRIM25 (previously believed to be present only in the cell cytoplasm) is also present in the cell nucleus, which is the same cellular location where flu replication occurs.

Sawyer and Meyerson are now looking to further investigate the role TRIM25 plays in cross-species transmission of influenza.

More studies are needed, but Krug believes new therapeutics could be designed to block the NS1 protein produced by the flu virus, hobbling its ability to evade the human immune system.

“If you could somehow block NS1 from acting, you could block all strains of the virus,” he says.

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Faculty careers can progress in many directions

Anonymous — Tue, 17 Oct 2017 06:00:00 +0000

Faculty careers can progress in many directions Anonymous (not verified) Tue, 10/17/2017 - 00:00

Viviane Callier

The canonical story of faculty productivity goes like this: A researcher begins a tenure-track position, builds their research group, and publishes as much as possible to make their case for being awarded tenure. After getting tenure, increased service and administrative responsibilities kick in and research productivity slowly declines. But now, a new study shows that, in computer science at least, the majority of faculty members have different—and more idiosyncratic—productivity trajectories. “There are lots of ways people make careers in academia,” says Daniel Larremore, professor of computer science at the University of Colorado in Boulder and one of the study’s lead authors. “There’s some space to revisit our expectations.”

Based on a comprehensive hiring and promotion dataset and a publication database for all 2453 computer science professors in the United States and Canada, Larremore and his co-authors found a huge range of publication trajectories, including the canonical one as well as many variations. That variability was not previously apparent because earlier studies of scholarly productivity typically focused on small datasets and were biased toward high achievers such as Nobel laureates, says Roberta Sinatra, assistant professor at the Central European University in Budapest.

Larremore’s team found that some faculty members remain very productive after tenure, with their publication rate peaking late in their careers and then declining abruptly. Others experience a productivity decline in the first few years on the tenure track, only to see an uptick in their fifth or sixth year. And still others don’t publish much early on but continually increase their output over the course of their careers. “Even though we have a canonical story about what a career in academia looks like, people are all over the map in reality,” Larremore says.

Ultimately, the authors write in the paper, “[t]his diversity in overall productivity, combined with the observation that an individual’s highest impact work is equally likely to be any of his or her publications, implies there are fundamental limits to predicting scientific careers.” For Jevin West, assistant professor in the Information School at the University of Washington in Seattle, that’s a good thing. “I don’t want young scholars to think their trajectory is somehow predestined,” he says. “There’s all sorts of things that lead to big discoveries.” However, cautions Henry Sauermann, associate professor of strategy at the European School of Management and Technology in Berlin, “the paper doesn’t tell us if all these paths are similarly successful in terms of getting tenure.”

It’s important to recognize that tenure committees rely on more than publication counts when evaluating candidates, says Donna Ginther, a professor of economics at the University of Kansas in Lawrence who studies scientific labor markets. These committees also take into account “the impact of the publications, and what the outside letter writers who are experts in the field have to say about the quality, quantity, and impact of the work,” Ginther says, which “may weigh more than the number of publications they’ve produced.” Larremore also emphasizes that publication count doesn’t necessarily reflect the true impact of a scholar’s work. “If you make a software package and it is used by thousands of hospitals, that may be a bigger contribution than five publications,” he says.

In light of the significant variation the new study reveals, funding agencies and hiring, tenure, and promotion committees need to appreciate the diversity of contributions and unpredictability of trajectories, the authors suggest. Evaluators who assume candidates should follow the canonical path may fail to reward people who are following different paths and end up missing out on talented researchers who still have great contributions to make, Sinatra agrees.

Although the data revealed a wide variety of career trajectories, there were also some notable trends. For one thing, men and women follow the canonical trajectory at equal rates, though men showed slightly higher initial and peak productivities. It’s not clear whether those differences are changing over time, moving toward parity in more recent cohorts, or whether differences at the time of hiring become exacerbated as careers progress. The researchers also found that faculty members at more prestigious institutions are more productive initially and have higher peak productivity, reflecting the higher publishing demands at higher-ranked institutions, Ginther notes. “You really need to know what you are getting into before you show up,” she says. “The postdoc can be used as a time to get a lot of work started so you get your publications rolling before you start on that tenure-track clock.”

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Does faculty productivity really decline with age? New study says no

Anonymous — Tue, 17 Oct 2017 06:00:00 +0000

Does faculty productivity really decline with age? New study says no Anonymous (not verified) Tue, 10/17/2017 - 00:00

Lisa Marshall

For 60 years, studies of everyone from psychologists to biologists to mathematicians have shown the same remarkably similar academic research trajectory: Scientists publish prolifically early in their careers, peak after about five years, get tenure and begin a long slow decline in productivity.

But a new ��񱦵� study published today in the journal PNASsuggests that stereotype is misleading.

“We found that only about one-fifth of researchers have careers that actually look like that expected curve, and the other 80 percent exhibit a really diverse set of productivity trajectories,” says first author Samuel Way, a postdoctoral researcher in the Department of Computer Science.

Way notes the long-standing narrative has long served as an unofficial yardstick by which faculty are measured, influencing hiring committees to look for young prolific publishers, and some higher education watchdogs to call for the reinstatement of mandatory retirement or other incentives to nudge older faculty to retire.

“What this study tells us is that productivity comes at various stages and there are a lot of different ways to have a successful career as a scientist,” Way says.

The study is co-authored by Allison Morgan, a PhD student in computer science, and Aaron Clauset and Daniel Larremore, assistant professors rostered in computer science and in the BioFrontiers Institute.

The team looked at more than 200,000 publications from 2,453 tenure track faculty in 205 computer science departments in the United States and Canada.

On average, the stereotypical “rapid-rise, gradual-decline” curve held true. But when the researchers used modern computational methods to drill down to individual patterns, they found the curve to be a “remarkably inaccurate” description of most professors’ careers. A considerable number started off slow publication-wise and showed late-career spikes. Others published at a steady rate over time.

It’s important for the public to know that there are professors who do incredible work all throughout their career and also for young faculty to know there is more than one way to be successful.”
–Daniel Larremore

The study also found:

Scientists today are publishing significantly more papers annually on average (four versus one in 1970), likely due to greater collaboration and a trend toward publishing more incremental findings.
Fifty percent of papers are authored by about 20 percent of faculty.
Women published about 46 percent fewer papers than men early in their career, even when trained and hired at similarly ranked institutions. (More research is underway to determine why. Some theorize pregnancy and childrearing responsibilities, and a tendency for women to volunteer more, could be factors.)

While the study looked only at computer scientists, Way believes its findings likely translate to other disciplines.

The paper is the latest in a series of “science of science” papers using computational social science to explore trends in faculty hiring and productivity. Previous papers looking at computer science, business and history have shown that both prestige and gender matter when it comes to who becomes a faculty member and where.

“If you choose a history professor in the United States at random, chances are better than 50 percent that professor came from one of eight universities,” says Larremore, senior author on the newest paper, noting a disproportionately small number of universities produces a disproportionately large number of faculty. “Those eight departments are the ones deciding the research agenda for an entire field. At the same time, it is not clear how much prestige is a good signal of quality.”

Larremore and Clauset’s research, conducted at ��񱦵� and at the nonprofit Santa Fe Institute, has also shown the prestige hierarchy underlying faculty hiring has a greater impact on women than on men.

“If a man and a woman both get PhDs from a decent state school, she will tend to get a job at a less prestigious school than he does. If they both went to a highly ranked school, she will get an even lower-ranking job than he does,” Larremore explains.

Larremore and Way both caution publication rates cannot, in and of themselves, serve as a reliable measure of career productivity, as some professors do more mentoring and teaching.

They hope the most recent paper will send a message to faculty members, those in charge of hiring and evaluating them, and the public. Over time, the team hopes their “science of science” papers will help shape policy, says Way.

“The more we understand what faculty need to be successful in science, the more we can go about improving policies to set them up for the best careers possible.”

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BioFrontiers postdoctoral fellow first Coloradan to receive prestigious award

Anonymous — Thu, 12 Jan 2017 15:00:50 +0000

BioFrontiers postdoctoral fellow first Coloradan to receive prestigious award Anonymous (not verified) Thu, 01/12/2017 - 08:00

CUBT - ��񱦵� Today

If an anti-aging regimen that involves telomeres – part of the human chromosome – sounds too good to be true, it probably is, says Jens Schmidt, a postdoctoral fellow in the Cech Lab at ��񱦵�’s BioFrontiers Institute.

“There are all these products out there that say ‘hypercharge your telomeres!’ But if you do that in cells that are predisposed to turn into cancer cells you might be in trouble,” says Schmidt, who was just named the first Coloradan to win the prestigious Damon Runyan-Dale Frey Breakthrough Award for cancer research.

Telomeres are elongated caps at the ends of each of our 46 chromosomes which, like the tips of shoelaces, serve to protect our precious DNA from fraying. As telomeres shorten, cells wither and die, and we age. Consequently, telomere preservation – via everything from gene therapy to dietary supplements – has been broadly viewed as the modern-day Fountain of Youth. But Schmidt sees telomeres in a darker light. When preserved via a naturally-occurring enzyme called telomerase, they can also immortalize some cells that are meant to stop dividing and die. Left to proliferate, those cells can lead to cancer.

“Telomere maintenance is one of the few key things cancer needs to survive,” says Schmidt.

With a brand new baby at home, the 33-year-old, Berlin-born scientist aims to use the $100,000 award to further his groundbreaking research exploring precisely how the telomerase enzyme finds, attaches itself to and replenishes telomeres. Ultimately, he and others envision a new generation of targeted cancer drugs which would work by inhibiting that cell-preserving process in cancer cells, while sparing healthy ones (thus avoiding the hair loss and other side effects that cancer drugs can bring).

“Jens has made a significant contribution to the field of understanding telomerase, which has big potential to impact cancer treatment,” says Yung Lie, chief scientific officer for the Damon Runyan Cancer Research Foundation. “He has a developed a very unique way of looking at this in a way that was not technologically possible before.”

To understand just how a telomerase enzyme replenishes a fraying chromosomal end, Schmidt first set out to learn how the two find each other in the relatively vast open space inside the cell. “It’s like if you have 10 buddies and you all go to a Broncos game and you scatter at the stadium,” he explains. “How are you going to find each other without cell phones? What are the chances you’ll just bump into each other? And if you do, how do you keep holding hands to make sure you don’t lose each other again?”

In August, Schmidt and his mentor Nobel laureate Thomas Cech coauthored a paper in the journal Cell which shed significant light on the process.

Schmidt developed a method using the CRISPR genome editing tool to attach fluorescent tags to telomerase enzymes and telomeres. Then he used a high-powered microscope to spy on their movements inside the nuclei of living human cancer cells. A resulting video shows telomerase zipping around the nuclei at a frenzied pace, bumping into telomere after telomere thousands of times before settling in on some, resting there for up to 8 minutes, then zipping away. Schmidt suspects the telomerase is adding DNA sequences as it rests there, elongating the telomere. With his next study, he hopes to find out for sure. “I want to understand this whole process in gory detail.”

Originally from Germany, Schmidt attended the Freie Universitat in Berlin before earning a doctorate in biology from the Massachusetts Institute of Technology and coming to ��񱦵� to study with Cech under a postdoctoral fellowship sponsored by the Damon Runyon Cancer Research Foundation. Of 27 fellows who applied for the Breakthrough Award, he was one of three recipients.

He notes that in some cases, as with the stem cells that yield skin and hair, telomere preservation is indeed beneficial. But when it comes to dietary supplements that aim to promote longevity by enhancing the process, he warns: Buyer beware. None have been approved by the Food and Drug Administration and whether they do anything to truly influence telomeres remains uncertain.

And if they do? “You might look younger,” he says. “But you also might be boosting your cancer risk.”

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Dan Knights Adventure Continues

Anonymous — Wed, 23 May 2012 06:00:00 +0000

Dan Knights Adventure Continues Anonymous (not verified) Wed, 05/23/2012 - 00:00

BioFrontiers

IQ Biology graduate's adventure continues

Dan Knights is a humble guy, with very little reason to be humble. A short list of his titles includes high school math teacher, computer scientist and the 2003 Rubik’s Cube World Champion. He has appeared on the Today Show, The Discovery Channel and as an expert on National Public Radio’s “Wait, Wait… Don’t Tell Me.” Dan has co-authored 21 journal publications, including two in Science and three in Nature.

He is interested in applying machine learning and computational statistics to challenges in biology, genomics and engineering. He is also the first student to graduate from BioFrontier’s Ph.D. certificate program in Interdisciplinary Quantitative Biology, or IQ Biology.

“The IQ Biology program encouraged me to continue to straddle the boundary between computation and biology,” said Dan “It exposed me to a new group of scientists and strengthened my foundations in the life sciences.”

Dan defended his thesis work in April 2012, which also earned him the Outstanding Dissertation Award from CU-Boulder’s College of Engineering and Applied Science. During his graduate studies, he spent much of his time in the lab of BioFrontiers faculty member Rob Knight, researching the microbiome.

Dan's advice for incoming graduate students is simple and effective:

Dan's advice for incoming graduate students is simple and effective: Learn programming and learn how to write code. Don't be afraid to branch out and explore other disciplines during lab rotations. You might be surprised how these connections make you better at what you do. For an impressive list of Dan's publications, visit his website.

The microbiome is the enormous collection of bacterial species that coexist in and on living organisms, including humans, and contribute substantially to our health and disease. The bacteria can be identified indirectly through their DNA genomes, but these experiments generate a vast amount of information. Making sense of all that information required Dan’s computer science expertise.

Dan recently accepted a tenure-track faulty position as an assistant professor of Computer Science at the University of Minnesota, Twin Cities Campus. Before he heads to the City of Lakes, Dan is making a year long stop at The Broad Institute of MIT and Harvard in Cambridge, Mass. to extend his research by doing post-doctoral work. His focus will be a mix of microbiome analysis, and a study of gut microbiota and the human immune response.

“It is unusual for a graduate student to jump right into a tenure-track faculty position, but Dan is unusually talented, and his accomplishments in both computer science and genomics served him well on the job market,” said Tom Cech, Director of the BioFrontiers Institute. “He sets a high standard for students in the IQ Biology program, and we wish him the very best.”

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2012 Butcher Seed Grants Awarded

Anonymous — Thu, 10 May 2012 06:00:00 +0000

2012 Butcher Seed Grants Awarded Anonymous (not verified) Thu, 05/10/2012 - 00:00

BioFrontiers

2012 Butcher Seed Grants Awarded

Ten recipients of the 2012 Butcher Seed Grant Awards were recently notified of their winning proposals in interdisciplinary bioscience. These grants bring critical funding to many of Colorado’s top academic researchers wanting to expand their scientific discoveries, and build new collaborations that span disciplines and academic institutions. This year’s winning proposals are collaborative efforts between researchers at the ��񱦵�, The University of Colorado Denver and National Jewish Health. Winners will receive a maximum of $100,000 to further their research projects.

These proposals offer an exciting look into the biomedical research going on in Colorado, covering everything from therapeutics for heart failure using phenotypic screening, to using live cell imaging to change our understanding of cells. The awardees are:

Investigating phospholipid asymmetry with specific peptide probes

Xue, Ding (PI)
Department of Molecular, Cellular and Developmental Biology, ��񱦵�
Yin, Hang (Co-PI)
BioFrontiers Institute, Department of Chemistry and Biochemistry, ��񱦵�

Discovery of novel therapeutics for heart failure by high throughput phenotypic screening

McKinsey, Timothy (PI)
Division of Cardiology/Department of Medicine, University of Colorado Denver
Reid, Brian (Co-PI)
Department of Pharmaceutical Sciences, University of Colorado Denver

Biological applications of novel shape-persistent, three-dimensional organic molecular cages

Liu, Xuedong (PI)
Department of Chemistry and Biochemistry, ��񱦵�
Zhang, Wei (Co-PI)
Department of Chemistry and Biochemistry, ��񱦵�

Structural studies of DUF1220 protein domains

Sikela, James (PI)
Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine
Pardi, Arthur (Co-PI)
Department of Chemistry and Biochemistry, ��񱦵�

Chemical synthesis and biological characterization of homogeneous human precursor IL-1α glycoforms

Tan, Zhongping (PI)
BioFrontiers Institute, Department of Chemistry and Biochemistry, ��񱦵�
Dinarello, Charles (Co-PI)
Department of Medicine and Immunology, University of Colorado School of Medicine

Role of the Sf3a mRNA splicing complex in innate immunity regulation

Alper, Scott (PI)
Integrated Department of Immunology, National Jewish Health
Leach, Sonia (Co-PI)
Center for Genes, Environment and Health, National Jewish Health
Blumenthal, Thomas (Co-PI)
Department of Molecular, Cellular and Developmental Biology, ��񱦵�

Revolutionizing the way we look at cells: Defining novel organelles by harnessing the power of proteomics and live cell imaging

Ahn, Natalie (PI)
BioFrontiers Institute, Department of Chemistry and Biochemistry, ��񱦵�
Palmer, Amy (Co-PI)
BioFrontiers Institute, Department of Chemistry and Biochemistry, ��񱦵�

4-dimensional flow cardiac MRI for diagnosis of pulmonary hypertension

Fenster, Brett (PI)
Division of Cardiology, National Jewish Health
Hertzberg, Jean (Co-PI)
Department of Mechanical Engineering, ��񱦵�
Schroeder, Joyce (Co-PI)
Department of Radiology, University of Colorado School of Medicine

Cardiac cell mechanobiology

Leinwand, Leslie (PI)
BioFrontiers Institute, Department of Molecular, Cellular and Developmental Biology, ��񱦵�
Anseth, Kristi (Co-PI)
BioFrontiers Institute, Department of Chemical and Biological Engineering, ��񱦵�

The Butcher Symposium began in 2002 as a grassroots effort to bring together scientists from across the CU system to create collaborations and share data. Butcher Seed Grants were awarded in 2002, 2005, 2007 and 2009 to fund potentially transformative new scientific pilot projects that required researchers with different expertise to work together to address critical challenges in the biosciences.

“The 2012 Butcher Seed Grant award winners really represent what we can achieve in the biosciences by using interdisciplinary approaches, said Leslie Leinwand, Chief Scientific Officer at the BioFrontiers Institute. “By approaching human health challenges with the tools and minds of many types of scientists, we make a deeper impact in developing new solutions.”

In addition to the Butcher Seed Grants, additional funding was provided for one winning proposal under the Elliman Family Award in Collaborative Stem Cell Research. The awardee for the Elliman Family Award is:

Treatment of Lipoprotein Lipase (LPL) deficiency with induced pluripotent stem cell (iPSC) technology

Eckel, Robert (PI)
Division of Endocrinology, Metabolism and Diabetes; Division of Cardiology; Department of Medicine; Colorado Clinical and Translational Sciences Institute, University of Colorado Anschutz Medical Campus
Olwin, Bradley (Co-PI)
Department of Molecular, Cellular and Developmental Biology, ��񱦵�
Chen, Jiang (Co-PI)
Department of Dermatology, Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado Anschutz Medical Campus
Wang, Hong (Co-PI)
Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus

In keeping with the tradition of previous Butcher Symposia, recipients of the 2009 Butcher Seed Grants presented the results of their research during the Butcher Symposium in November of 2011. From developing new methods to measure the risk of premature birth to discovering the role of genetics in the development of chronic obstructive pulmonary disease, their research represented fields as diverse as mechanical engineering, biochemistry and computer science—often in the same presentation—and included collaborators from several Colorado academic institutions.

The Butcher Program was founded through the generosity of long-time CU supporters Charlie and Jane Butcher, who saw the potential for “big picture” scientific thinking and creative cross-discipline research to transform lives. The seed grants were awarded this year thanks to continued support from the Butcher family, CU-Boulder and Anschutz Medical Center leaders, and the CU President’s Office.

In addition to supporting the symposium and the seed grants, their support established the Charlie Butcher Award in Biotechnology to recognize scientists from around the world who are using interdisciplinary science to make a significant impact on human welfare and health. The 2011 award went to Nobel Laureate, Rogen Tsien from the University of California, San Diego, who developed fluorescent proteins, which revolutionized imaging live cells.

Additional information on the Butcher Program and on Charlie and Jane Butcher, is located on our website.

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