Computational Biology

Work with bees could unlock potential strength of natural designs in new materials

Anonymous — Mon, 17 Sep 2018 06:00:00 +0000

Work with bees could unlock potential strength of natural designs in new materials Anonymous (not verified) Mon, 09/17/2018 - 00:00

Josh Rhoten

The natural world has had billions of years of evolution to perfect systems, creating elegant solutions to tricky problems. CU Boulder Assistant Professor Orit Peleg’s work hopes to illuminate and explore those solutions with the long-term goal of applying the answers she finds to the materials we interact with daily.

Her most recent research with bees, recently published in Nature Physics, is a small step toward that goal. The project looked at the honeybee cluster swarms that hang in cone shapes from tree branches and are made up of hundreds of individual insects clinging to one another. While these swarms are hundreds of times the size of a single organism, the individual bees that comprise it are able to maintain the structure’s stability despite wind and gravity forcing changes in the overall shape.

Peleg, who is based in the Computer Science Department and the BioFrontiers Institute at CU Boulder, conducted the research during her time as a post-doctoral fellow at Harvard in 2017. She said the use of bees for the project “was a bit crazy,” but presented a good opportunity to work more on modeling and testing these types of systems at a low cost and with relatively simple imaging equipment.

“It is a good way to connect experiments to theory and go back and forth until we have a good understanding of the system,” she said.

The project tried to untangle how the cluster stayed together in various conditions by attaching one to a board that was shaken with varying amplitude, frequency and duration. The results showed that horizontally shaken clusters spread out to form wider, flatter cones, adapting to the movement, but also going back to normal given time. Something similar happened with sharp, pendular movements, but measurements before and after showed that the flattened cones deform less and relaxed faster than the elongated ones. Meanwhile, vertical movement put less strain on the structure which, in turn, required less change from the bees to adapt to the motion.

In the end, the experiment confirmed what Peleg’s agent-based simulations predicted and opened up new questions.

“Our goal in this experiment was to try to pinpoint local rules for behaviors of bees that dictate the mechanical stability of the structure. A bee on one side of swarm can’t say what another bee at the other side of the swarm is doing. It can only say what is happening in its local environment,” Peleg said. “So, by creating this structure, they have to solve this mechanical problem of stability by only using local information.”

But how do they know to do this? Or why? Peleg’s hypothesis is that individual bees respond to the strain they feel during movement, changing their position in the swarm to match it.

“We can think about a local role, where a bee senses those deformations through connections to other bees. If this exceeds a certain threshold, it moves around to address that,” she said. “It doesn’t consider up or down, it just takes the local gradient information. Going up gradient (magnitude) makes it harder for individual bee, but better for the swarm overall.”

Peleg is part of the Multi-functional Materials Interdisciplinary Research Theme at CU and said this work fits well with that theme’s goal of exploring new materials and applications. While there is still more work to be done in studying the fundamental biology at work, she said this research could have applications in swarm robotics or the creation of materials that can sense their environment and respond to it.

“There is a clear connection to structures that insects make like swarms or ant-towers, for example, that are dynamic and respond to things like temperature or mechanical changes,” she said. “The grandiose vison of this, which we are still far away from, is the creation of construction materials that can sense and respond to earthquakes and become more stable in the same sort of way.”

Peleg has an apiary on East Campus and is planning on continuing this kind of work and this project in particular. Specifically, she said there was still work to be done with imaging the inside of the swarms to help with overall understanding of how this process works.

“We still need to look at the internal structure of the swarm through x-rays, for example, as that is completely unknown right now and could be informative,” she said.

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IQ Biology Blog: Computing Machinery and Mouse Genomes

Anonymous — Tue, 10 Mar 2015 06:00:00 +0000

IQ Biology Blog: Computing Machinery and Mouse Genomes Anonymous (not verified) Tue, 03/10/2015 - 00:00

BioFrontiers

I recently attended the 2014 Association for Computing Machinery Conference on Bioinformatics, Computational Biology, and Health Informatics (ACM BCB) with fellow IQ Biology student Joey Azofeifa and our advisor Robin Dowell. The conference had many interesting talks, ranging from theory-heavy explanations of algorithm improvements to very applied talks on using computational analysis for medical procedures. Joey presented his work on FStitch, a tool for measuring RNA transcription with GRO-seq data, which is soon to be published in the conference journal. His talk went very well and he fielded many good questions from interested attendees. In addition, Robin was a panelist for the “Women in Bioinformatics Panel” which addressed specific issues women might face in the field of bioinformatics.

I presented my poster titled “Inferring Ancestry in Mouse Genomes using a Hidden Markov Model”, where I showed my work on determining haplotype block inheritance using single-nucleotide polymorphism data from two selectively bred mouse strains and six of the eight ancestor strains that they were bred from (the other two ancestor strains haven’t been sequenced). To infer ancestry, I used a hidden Markov model (HMM)- a probabilistic model used to find the maximum likelihood path through a state machine. The poster session was great and I ended up having many visitors over during the two-hour timeframe. Some were simply intrigued by the pretty pictures and wanted to know what an HMM was, while others had worked on similar inheritance problems and had good questions about my process. I even spoke with a group that works with the mice strains we used and have imputated the genomes of the two unsequenced ancestor mouse strains, so I’m now looking into incorporating this data in my model.

The conference was held in Newport Beach, CA and while it was hot and sunny the entire weekend, I unfortunately never got a chance to visit the beach. I was lucky enough, however, to have a good friend who lives in the area and whom I hadn’t seen in over a year, so I got to spend some quality time with her. We were trying to plan a trip to see each other soon anyways, so it was really lucky that the conference happened to be in her area!

Currently, other members of the Dowell Lab and I are in the process of writing a paper on the sequencing of the two selectively bred mice strains, which will include my ancestor inference piece as a section. We then hope to extend my work by refining our methods, running simulations, and including the imputed genomes of the missing ancestors. This can hopefully be published as a conference paper later this year.

IQ Bio Blog: Night at the Museum

IQ Bio Blog: Science in pictures

IQ Bio Blog: Workshop on Genomics

IQ Biology Blog: On the leading edge

IQ Biology Blog: Understanding RNA

IQ Biology students win fellowships from NSF

Science is Hard

IQ Biology Program Wins IGERT

When the student becomes the mentor

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Sie Fellows focused on quality of life in Down syndrome

Anonymous — Thu, 10 Jul 2014 06:00:00 +0000

Sie Fellows focused on quality of life in Down syndrome Anonymous (not verified) Thu, 07/10/2014 - 00:00

BioFrontiers

Mary Allen holds up a valentine sent to her from a childhood friend. It sits in her cubicle where she is hard at work tearing apart genomic data looking for patterns. This friend, who has Down syndrome, is part of the reason that Allen, a postdoctoral researcher in Robin Dowell’s lab at the BioFrontiers Institute, became interested in studying aneuploidy. Aneuploidy means that cells have too many, or too few, of one or more chromosomes. In the case of Down syndrome, there is an extra copy of chromosome 21. Allen is exploring what makes people with this extra chromosome survivors.

“Down syndrome is actually not all that survivable,” says Allen. “Only 25 percent of embryos with three copies of chromosome 21 survive to live birth. These people who are surviving and living long lives have something in their DNA—from their genetic background—that is helping them.”

Down syndrome is the most commonly occurring chromosomal condition and more than 400,000 people in the United States are currently living with it. Allen is right about them being survivors. According to the Global Down Syndrome Foundation, life expectancy for people with the syndrome has increased dramatically from 25 years in 1983 to 60 years now, due in part to better educational programs, health care and support from families and communities.

Allen is taking genetic sequencing data from people with Down syndrome and their parents to understand how that extra copy of chromosome 21 puts this population at higher risk for health issues such as heart defects, thyroid conditions, leukemia, Alzheimer’s disease, and respiratory and hearing problems. She is also trying to understand why they are at lower risk for heart attack, stroke, and solid tumor cancers. Allen isn’t out to find a cure for Down syndrome. Her goal is to find what in their DNA is helping these survivors, and how can we design targeted molecular therapy to help them have better lives.

“Once you have had a friend with Down syndrome, stopping the occurrence of the syndrome isn’t on the table,” says Allen. “They are just such great people.”

Allen recently was awarded a Sie Foundation Postdoctoral Fellowship to continue her Down syndrome research for the next two years. This fellowship was created under the Anna and John J. Sie Endowment Fund for the BioFrontiers Institute, which is targeted specifically at funding research to prevent the cognitive and medical ill effects associated with the extra chromosome 21. The fellowship is offered as a collaboration between BioFrontiers and the Linda Crnic Institute for Down Syndrome at the University of Colorado, Anschutz Medical Campus.

The BioFrontiers Institute also awarded Sie Fellowships to Geertruida Josien Levenga of CU-Boulder’s Institute of Behavioral Genetics and to Alfonso Garrido-Lecca of CU-Boulder’s Department of Molecular, Cellular and Developmental Biology. Dr. Levenga is a neuroscientist whose research holds promise for ameliorating the seizures that afflict so many individuals with Down syndrome. Dr. Garrido-Lecca will test the hypothesis that alteration of microRNA levels in individuals with Down syndrome contributes to some of their health challenges.

Dr. Allen sees the new fellowship as welcome news for her work. Research funding for Down syndrome has always been extremely low. The National Institutes of Health in 2012 allocated only $50 in research funding per person living with the condition, versus $270 for Fragile X research, $329 for multiple sclerosis research and $2,867 for cystic fibrosis research. Individuals with Down syndrome have special health needs, like heart conditions and decreased immunity, which can be helped by further research. In addition, since Alzheimer’s disease, leukemia, low muscle tone and weight gain are seen at a high incidence in people with Down syndrome, researching the syndrome may lead to treatments for these associated disorders in the broader population.

“Research on the smaller ear canals of people with Down syndrome is now helping people who suffer from deafness and other auditory disorders,” says Allen. “Unlocking the cellular processes behind one disorder can help us with so many others.”

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CAREER scientist thrives at the intersection of research and teaching

Anonymous — Fri, 21 Mar 2014 06:00:00 +0000

CAREER scientist thrives at the intersection of research and teaching Anonymous (not verified) Fri, 03/21/2014 - 00:00

Meagan Taylor

Most university faculty divide their time between research activities, teaching and service to their institutions, sometimes putting in hundreds of hours weekly to accomplish the job’s demands. Being able to shine in all of these areas is a rare accomplishment, especially for newer faculty. For BioFrontiers faculty member Robin Dowell, juggling these responsibilities is somewhat second nature.

“With respect to components of academia, I firmly believe that these are difficult to separate,” she says. “The best way to deeply understand scientific concepts is to get your hands dirty— actually perform an experiment, write a program, or solve a math problem — or to teach the concepts to someone else. In the best-case scenarios, you do both.”

Her ability to apply this philosophy recently earned Dowell the National Science Foundation’s most prestigious award for junior faculty, the Faculty Early Career Development (CAREER) grant. Providing five years of support totaling more than $650,000, the grant recognizes emerging investigators who excel at combining teaching and research in ways that directly impact their institutions and the broader community. Dowell is one of only ten scientists nationwide in the field of molecular and cellular bioscience who have received the award so far this year.

The CAREER program requires scientists to complete specific aims in both teaching and research. Successful candidates have designed projects in which their research feeds into their teaching goals and vice versa, creating a long-term cycle that advances both aims. Projects are also expected to meet institutional needs, such as providing students with mentored external development opportunities or promoting interdisciplinary research.

Dowell prefers the term “antedisciplinary” in her lab’s approach, a term coined by her graduate mentor, Dr. Sean Eddy. Given her and her students’ concentrations in computer science, statistics, molecular biology and genetics, she defines the concept as “following problem wherever it leads you.”

“I have a hard time when people ask me how I integrate such diverse fields,” she says. “It isn't about integrating fields, areas or components, but rather ignoring those kinds of boundaries.”

The CAREER project embraces this philosophy by providing two unique educational activities for students while furthering the Dowell lab’s continuing research on the molecular impact of aneuploidy. Down syndrome is a well-known example of aneuploidy, which occurs when a person has more copies of a chromosome than normal.

Using computational models of biological processes and experiments on yeast cells, the Dowell lab will explore how regulators—genes that affect the function and form of other genes— affect the early processes of genetic expression, called transcription.

Dowell describes her research in musical terms. If the human genome is the score for a symphony, transcription is like the music heard from that score. In genetics, a regulator gene performs the work of the musical conductor, controlling qualities such as tempo and volume.

While regulators in the human genome number about 1,800, having too many of these conductors in a particular cell can throw off the music. Aneuploidy is an example in which the dose of regulators has altered expression of genes, causing deleterious affects for people with Down syndrome.

“We understand that transcription is affected by aneuploidy, but we don’t know how it works at the molecular level,” Dowell says.

The educational component of project contains two unique objectives that encourage students to engage in external opportunities that contribute to their education and community. The first objective is to establish a permanent iGEM team at CU. iGEM, or international Genetically Engineered Machine, is the world’s foremost synthetic biology competition for undergraduates. Last year’s CU team won the gold medal at the North American competition for their “DIY Biology” project to create a set of low-cost tools for performing synthetic biology.

The second objective is to better engage scientists in understanding Responsible Conduct of Research (RCR) by creating an interactive game. RCR encompasses professional norms and ethical principles scientists must use in the performance of their work.

“The game will not only train scientists in an engaging and interactive manner but also will enable studies into how peer pressure influences ethical behavior.” Dowell wrote in her CAREER grant application. “In the end, the long term impact of creating honest, intelligent and creative scientists is incalculable.”

More information on antedisciplinary research, iGEM and aneuploidy can be found on the Dowell Lab website.

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2014 Butcher Seed Grant Winners Announced

Anonymous — Wed, 12 Mar 2014 06:00:00 +0000

2014 Butcher Seed Grant Winners Announced Anonymous (not verified) Wed, 03/12/2014 - 00:00

BioFrontiers

Butcher Seed Grant Winners

Seven recipients of the 2014 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 across the University of Colorado system and National Jewish Health. Winners will receive between $70,000 and $75,000 to further their research projects.

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, 2009 and 2012 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 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, and CU-Boulder and Anschutz Medical Center leaders.

In addition to supporting the symposium and the seed grants, the support from the Butchers also 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 2013 award went to biologist Jack Szostak of Harvard University whose discovery of how chromosomes are protected by telomeres won him the 2009 Nobel Prize in Physiology or Medicine. For additional information on the Butcher Program and on Charlie and Jane Butcher, please visit our site.

This year’s winning proposals offer an exciting look into the biomedical research going on in Colorado, covering everything from studying seizures in the brain using small fiber optical devices, to finding ways of using the vast collection of microbiome data for diagnosing disease. The awardees are:

“Optimized deep-brain imaging of activity in over a hundred neurons for imaging seizures”

Emily Gibson (PI) - Department of Bioengineering, University of Colorado, Denver, Anschutz Medical Campus
Juliet Gopinath (Co-PI) - Department of Electrical, Computer and Energy Engineering, University of Colorado, Boulder
Victor Bright (Co-PI) - Department of Mechanical Engineering, University of Colorado, Boulder

“Developing a Platform for in vivo Imaging of Chronic Bacterial Infection”

Corrella Detweiler (PI) - Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder
Amy Palmer (Co-PI) - BioFrontiers Institute and Department of Chemistry and Biochemistry, University of Colorado, Boulder

“Single-molecule physical probing of glycan recognition by viral capsid proteins”

Robert L. Garcea (PI) - BioFrontiers Institute and Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder
Thomas Perkins (Co-PI) - JILA, NIST, Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder

“Conformational dynamics of dystrophin probed using single-molecule FRET”

Krishna Mallela (PI) - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Denver, Anschutz Medical Campus
David Nesbitt (Co-PI) - JILA, NIST Quantum Physics Division, Department of Chemistry and Biochemistry, University of Colorado, Boulder

“Extracting diagnostic signals from human microbiome data”

Aaron Clauset (PI) - BioFrontiers Institute and Department of Computer Science, University of Colorado, Boulder
Ken Krauter (Co-PI) - Institute for Behavioral Genetics and Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder
Matt McQueen (Co-PI) - Institute for Behavioral Genetics and Department of Integrative Physiology, University of Colorado, Boulder

“The Nano Rainbow: Multicolor Biolabels for Simultaneous Molecular Scale Tracking and Tailored Assays of Biological Agents”

Kevin Tvrdy (PI) - Department of Chemistry and Biochemistry, University of Colorado, Colorado Springs
Anatoliy Pinchuk (Co-PI) - BioFrontiers Center and Department of Physics and Energy Science, University of Colorado, Colorado Springs

“Targeted Delivery of Antioxidant Peptides to the Pulmonary Arteries for the Treatment of Pulmonary Hypertension”

Leah R. Villegas (PI) - Department of Pediatrics/Cardiovascular Pulmonary Research, University of Colorado, Denver, Anschutz Medical Campus
MyPhuong T. Le (Co-PI) - Department of Renal Medicine, University of Colorado, Denver, Anschutz Medical Campus

As a new extension of the Butcher seed grant program, grants for graduate students and postdoctoral fellows were sponsored by the student-led BioFrontiers Science Alliance. These monetary awards were made possible through generous donations from Roy Parker, Leslie Leinwand and Mike Yarus, and the BioFrontiers Institute. To be eligible, these research projects needed to be led by a CU-Boulder graduate student or postdoctoral fellow with a collaborator from a different department. These researchers were also required to present a poster about their work at the 2013 Butcher Symposium. A total of seven applications for the grants were submitted.

Two seed grants were funded at $2,000 and a third was funded at $1,500. The awardees are:

“Analyzing polyomavirus factories with double-helix super resolution microscopy”

Katie Heiser (Lead) - Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder
Anthony Barsic (Collaborator) - Department of Electrical, Computer, and Energy Engineering, University of Colorado, Boulder
Kevin Dean (Collaborator) - BioFrontiers Advanced Imaging Resource, University of Colorado, Boulder

“Characterizing structural variants in a mouse model of alcohol dependence”

Eitan Halper-Stromberg (Lead) - Department of Computational Biosciences, University of Colorado, Denver
Aaron Odell (Collaborator) - Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder

“Non-invasive monitoring of MMP activity of cardiac fibroblasts cultured under diseased and fibrotic microenvironment”

Jennifer Leight (Lead) - Department of Chemical and Biological Engineering, University of Colorado, Boulder
William Wan (Collaborator) - Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder

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BioFrontiers partners with Avery Brewing

Anonymous — Fri, 31 Jan 2014 07:00:00 +0000

BioFrontiers partners with Avery Brewing Anonymous (not verified) Fri, 01/31/2014 - 00:00

BioFrontiers

BioFrontiers partners with world’s oldest biotech industry: Breweries

In the basement of the Jennie Smoly Caruthers Biotechnology Building on CU-Boulder’s East Campus sits a machine that can sequence roughly 6 billion DNA segments in about a week.

By comparison, human DNA consists of roughly 3 billion bases, and it took more than a decade for the first human genome to be sequenced by an international team of scientists.

The machine, an Illumnia HiSeq2000, is the centerpiece of the BioFrontiers Institute’s Next-Gen Sequencing Facility, and it has become a critical piece of equipment for researchers across campus. But it’s also an important resource for the Front Range’s thriving biotech industry, which routinely relies on the facility for sequencing work.

The facility has partnered with all kinds of local biotech big hitters, including a company that makes biofuels and another that makes tests for genetic mutations. But in 2013, the Next-Gen Sequencing Facility forged a new relationship with a well-loved but less-obvious local biotech company: Boulder-based Avery Brewing.

“I would argue that brewing and brewing chemistry is one of the oldest biotechnologies in the world,” said Jim Huntley, director of CU-Boulder’s sequencing facility. “They do a lot of analysis on the quality of their product. Any biotech company does that. I don’t care if you’re making beer or you’re making an enzyme that’s used to catalyze some reaction; there’s always a degree of quality control.”

Huntley and Robin Dowell, an assistant professor at BioFrontiers, are helping Avery find a way to maintain its much-lauded beer quality less expensively by sequencing the genomes of six of the yeast strains used at Avery during the fermentation process.

An IPA that tastes like an IPA

The problem Avery wants to fix is the possible cross-contamination of yeast strains. Unlike large brewing operations, microbreweries use the same equipment to brew multiple types of beer using more than one yeast strain, which can occasionally lead to the yeast strains growing where they don’t belong.

The yeast used in the brewing process feeds on sugar to produce alcohol and carbon dioxide. But along the way, the yeast produces other products that affect the flavor of the beer, including fruity esters, buttery ketones and spicy phenolics. Different strains of yeast produce different flavors, and so using the correct yeast is key to brewing the desired beer.

“For example, our IPA is fermented with a different strain of yeast than our Belgian wit,” said Dan Driscoll, Avery’s staff microbiologist. “We occasionally see our Belgian wit yeast is growing in an IPA tank and that’s a problem because that yeast is incredibly phenolic so the resulting beer smells clovy and spicy. In the interest of consistency, we can’t call our IPA our IPA if it tastes and smells different than the last batch.”

[video:https://www.youtube.com/watch?time_continue=4&v=4yehwrdKRGM]

Though it’s rare, when cross-contamination occurs, the entire tank of beer, typically about 240 barrels, has to be flushed.

In the past, Avery has uncovered cases of cross-contamination by sampling the beer while it’s in the fermentation tanks, streaking the sample on an agar plate, putting the plate in an incubator and waiting 48 hours for the yeast to grow.

“What I said, being a microbiologist, when I first got here was, ‘It would be great if we could find a way to both identify this cross-contamination sooner and determine how severe it needs to be in order for us to start picking up on those off flavors,’ ” Driscoll said.

Driscoll, a veteran of the more traditional biotech industry, knew that Avery could purchase a machine that would allow it to quickly differentiate the yeasts based on their genetic codes. But there was a catch: the genetic codes were not known.

Through a connection in the biotech industry, Driscoll got in contact with Huntley, who said he might be able to help Avery with its problem.

“Since we get funding from the state to maintain and operate the facility and purchase equipment, we really want to engage with the local biotech communities and other regional research organizations to provide them access to cutting-edge instrumentation,” Huntley said.

Because Avery uses commercially available yeast strains, and because the microbrew industry has a culture of openly sharing techniques and tools, working with Avery could benefit Colorado’s entire brewing industry, which has a total annual economic benefit to the state of more than $400 million.

‘Think globally, sequence locally’

Avery provided Huntley with six of its yeast strains, including its house ale yeast, which is used in a half dozen of the brewery’s beers. At the Next-Gen Sequencing Facility, Huntley loaded the samples into the HiSeq 2000, which works by shredding multiple copies of the yeast’s DNA into tiny little pieces and then sequencing all those overlapping pieces at the same time to produce a coherent picture of its entire genetic code.

But just knowing the genetic code isn’t enough to solve Avery’s problem. Driscoll also needs to know exactly how the yeasts’ genetic codes differ from each other to be able to tell the yeast strains apart—which is where BioFrontiers researcher Robin Dowell comes in.

Dowell’s lab specializes in differences between yeasts, though she doesn’t typically study the strains that are used to brew beer.

“We focus on two strains that, from a genetic perspective, are about as different as any two random people,” Dowell said. “We look at inter-strain differences all the time, and what Avery really cares about is identifying strain differences they can actually leverage to say, ‘This strain is this one and that strain is that one.’ ”

Once the differences in the strains have been identified, Avery Brewing Company will be able to determine if a tank is contaminated with the wrong kind of yeast in a matter of hours rather than days. The contaminated beer will still have to be flushed, but the test will make it possible for Avery to free up the tank sooner, allowing them to start brewing another beer that they can actually sell.

For the Next-Gen Sequencing Facility, the continued partnership with Avery is just part of what they are charged to do—help strengthen the local biotech community.

“When the local biotech community is stronger, it allows for more startups and more product development, which brings more jobs to the area,” Huntley said. “As I always quip, ‘Think globally, but sequence locally.’ ”

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JSCBB Mini Symposium

Anonymous — Thu, 19 Dec 2013 07:00:00 +0000

JSCBB Mini Symposium Anonymous (not verified) Thu, 12/19/2013 - 00:00

BioFrontiers

JSCBB Mini Symposium Encourages Collaboration

It looks a lot like the other buildings on the CU-Boulder campus, with its rustic Italian-inspired tile roof and red brick, but the Jennie Smoly Caruthers Biotechnology Building (affectionately known by its inhabitants as JSCBB) is something quite different. It was designed to support those scientists and engineers whose research was driving them into other academic areas, and who wanted to use the best tools from other disciplines to do their work. This building houses engineers, biologists, chemists, biochemists, computer scientists and physicists. These are the CU faculty that speak “interdisciplinar-ese”.

In a building where a biochemist can have barbecue with a biofuels expert, good ideas are bound to proliferate. The challenge is getting these dedicated researchers away from their labs and talking to each other. It takes conversation to initiate collaboration. To help this process along, the JSCBB Mini Symposium was born.

The JSCBB Mini Symposium took place on July 29 with 15 faculty members presenting on topics that spanned from biomarkers for cancer, to tissue engineering, biofuels and the microbiome. Faculty members represented the groups in the JSCBB: the BioFrontiers Institute, the Division of Biochemistry and the Department of Chemical and Biological Engineering. JSCBB’s Butcher Auditorium was packed for all five sessions throughout the day.

“It’s sort of like being at an international conference. We’re hearing all these great talks and listening to incredible talent,” says BioFrontiers Institute Director, Tom Cech. “The best part is that we never have to leave the building.”

Talks during the day highlighted just how broad the research is at JSCBB. Ryan Gill, an associate professor in the Department of Chemical and Biological Engineering detailed the challenges of creating the genome of new bacteria that could break down biomass and turn it into biofuels.

These bacterial helpers have to be resistant to invaders, tolerant of solvents and good at breaking down cell structures. This work piqued the interest of BioFrontiers’ Rob Knight who is an associate professor of biochemistry studying the bacteria, fungus and viruses that populate the human gut, skin and mouth. These researchers, who have collaborated before, will likely meet up again on this challenge.

BioFrontier’s Tom Cech explained the importance of telomerase in the health of human cells, and its role in cancer. During a question session after his talk, BioFrontiers Chief Scientific Officer Leslie Leinwand mentioned that there are virtually no cancers that attack heart muscle tissue, one of her specialized areas of study. “Has anyone studied the telomerase in that tissue?” she asked.

Cech paused momentarily, thinking and replied: “Not that I know of. But we could do it,” he said…hinting at the possibility of a future collaboration between the two.

If the goal of the JSCBB Mini Symposium was to get these talented scientists and engineers communicating with one another, it was successful. Faculty members caught up with each other during the lunch break and reception. In addition, students had free reign to ask questions about the information they had seen during the event. Probably the best measure of success of this event is the desire by these very busy researchers to do it again—a goal that was more than met.

“This will be one of many,” says Distinguished Professor of Chemistry and Biochemistry, Marv Caruthers. “It’s something we should do twice a year…or maybe more.”

BioFrontiers researchers uncover new target for cancer research

BioFrontiers Scientist Tackles a Childhood Disease of the Heart

Kristi Anseth Lecture: "The Body Shop"

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Science is Hard

Anonymous — Mon, 18 Nov 2013 07:00:00 +0000

Science is Hard Anonymous (not verified) Mon, 11/18/2013 - 00:00

Joey Azofeifa

It must be said that I have had a very difficult time writing this blog-post. The reason, after a few too many cups of coffee, came clear to me: Science is Hard (and I worried if that’s what I should tell my readers). Certainly there are intellectual struggles in Science, the esoteric aspects of an algorithm, and the even more enigmatic explanations of it on StackOverflow, can be mind-numbingly painful. But the real reason that Science is Hard (at least from the perspective of a lowly and naïve graduate student) circumvents “advanced” material and is better understood as an emotional one.

At the point of a really innovative thought, the scientist exists outside the documented, outside the history. At such an apex, he or she is met with a flurry of emotions: motivation, passion, strength and, to a degree, reluctance. But why feel the fear? Did Richard Feynman feel the fear? Albert Einstein? Probably. No, definitely. Any truly original moment identifies the thinker as different and such a separation from the comfort of the known begets questions of assuredness, obligation and failure. And so, Science is Hard because the very nature of Science is to innovate, push-past and discover and these struggles bring along the unwelcome feelings of separation.

As someone who works at the interface of computer science and biology, let me tell you: I feel the fear. Not because I would presume to have had something truly original but because such an interface is so new, untouched and foreign that every step is fraught in new territory. New textbooks are created every year to describe the field of “bioinformatics” but with very little collective agreement. Why? Well I think there are just so few foundational principles for bioinformatics that consensus still waits; I mean it’s a chaotic, free-for-all.

Within this spinning cacophony, innovation is ripe for the picking and this reason (among others) motivated a move from a background in biology to a graduate degree in computer science. Should I emphasize my thesis again? I think so: Science is Hard. The move away from the comfortable pleasures of a biological background was/is hard. But don’t worry, here is the silver lining: it has been a wildly rewarding experience.

Without going into the gory details of my 2-hour nights of sleep, eye’s glazed by a terminal screen and the quiet jitters of too much caffeine, I can honestly say I am glad to have taken the plunge into computer science. Not only because the field of bioinformatics is “hot” but such a transition highlights the whole purpose of Science: to stand outside the comfortable.

Few biologists are willing to venture into the blackbox of computer science (and probably even fewer computer scientists dare walk into the realm of the wet-lab). Yet, the knowledge that a field frightens or intimidates is reason enough to walk into it. And in all honestly, it need not frighten. With so many new graduate programs emerging like BioFrontier’s Interdisciplinary Quantitative Biology Program more resources are available now more than ever to help smooth the transition between varying scientific disciplines.

It goes without saying: one must be willing to feel stupid for an indeterminate (seemingly infinite) amount of time. But there are moments, really great, exciting, outstanding moments (albeit, few in the beginning), when you start to make connections, drawing parallels between the two fields. And such connectivity cannot be described or written down, it is felt. It is the clichéd, quintessential “a-ha” moment that harkens to the archetype of a true scientist. Those willing to step outside the familiar will feel the fear, I can promise you that, but you will also feel strength of character that will better you both as a scientist and as a thinker.

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Genotypes, phenotypes, alternators and faulty wiring

Anonymous — Mon, 19 Nov 2012 07:00:00 +0000

Genotypes, phenotypes, alternators and faulty wiring Anonymous (not verified) Mon, 11/19/2012 - 00:00

BioFrontiers

Genotypes, phenotypes, alternators and faulty wiring

Robin Dowell understands machines of all kinds. The MCD Biology assistant professor and BioFrontiers faculty member has been restoring old cars since she was 14 years old. She rebuilt her first engine with her dad, who is a petroleum engineer. It was a 1977 Mercury Monarch and she drove it throughout high school.

After high school she rebuilt a 1976 Ford F150 truck and drove it to college, earning a double bachelors degree in the unlikely combination of computer engineering and genetics. She then went on to get a master’s degree in computer science and a doctorate in biomedical engineering. She still owns the truck.

“Cars are simple machines. If you have a really good mechanic, you can go from a single noise in the engine to a diagnosis. For example, a bad mechanic will see electrical problems and just replace the battery or maybe the whole alternator. You'll be back in two months or less with more electrical problems," she says. “Good mechanics can tell when it is the alternator failing and just replace the brushes or if the problem is actually due to some faulty wiring somewhere in the system. We need that ability to look at a symptom and follow it to the core problem.”

Dowell believes that part of the solution is in the genotype and phenotype of each person. Your genotype is the catalog of genes that build everything about you. Your phenotype is how you look, how you are put together, and to some degree, the kind of behaviors you exhibit.

In 2001, the Human Genome Project was completed after more than 1,000 scientists worldwide sifted through 3 billion bits of data in each human cell to map the ordering of all human genes. You have about 20,000 genes in a unique combination that makes you, you. Every time a baby is born, a new genome is created.

With all our newfound knowledge of the genes and how they influence our phenotype, scientists are eager to apply this to predicting disease in humans: if you have a specific gene combination, you are likely to get a specific disease. It turned out that it wasn’t that easy.

In 2009 Dowell and a team of scientists got up close and personal with Saccharomyces cerevisiae— a type of yeast best known for its starring role in the fermentation process of bread and beer. They sequenced the genome of a new individual strain of the famed fungus and narrowed their focus on only the genes required to keep the organism alive. As they were getting closer to narrowing down what kept the yeast alive, they were also getting further away.

Dowell and her team discovered that genetic sequencing made up only part of the roadmap to understanding each individual. It was also very complex genetic interactions across the entire network of genes that influenced phenotype: the same mutation in different individuals created different phenotypes because of unique interactions across the network.

“The genome gave us a parts list,” says Dowell. “Now we’ve realized that there is much more to understanding a genome than a simple parts list.”

It seems like not such a big deal when you are talking about yeast, but when you apply this to how drugs interact in individual humans, it becomes a bigger issue. The human condition becomes a moving target with constant mutations at a genetic level that affect the phenotype of each individual. Designing drugs that work effectively for all people, without killing any of them, becomes nearly impossible.

Dowell’s vision is to one day understand how genes influence disease susceptibility—a likely insurmountable goal for anyone but someone with her background in computer science and genetics. Like the Mercury Monarch engine she restored in her teens, she wants to be able to listen to the engine and know that it is not just the alternator that is going bad.

“That is what we’re missing in medicine right now,” she says. “We want to get to a mechanistic understanding of human beings. And to get there we have to know that it is all connected.”

You can read Robin’s paper, Genotype to Phenotype: A Complex Problem here.

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Robin Dowell

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BioFrontiers researchers uncover new target for cancer research

Anonymous — Wed, 24 Oct 2012 06:00:00 +0000

BioFrontiers researchers uncover new target for cancer research Anonymous (not verified) Wed, 10/24/2012 - 00:00

BioFrontiers

In a new paper released today in Nature, BioFrontiers Institute scientists at the University of Colorado in Boulder, Tom Cech and Leslie Leinwand, detailed a new target for anti-cancer drug development that is sitting at the ends of our DNA. Researchers in the two scientists’ laboratories collaborated to find a patch of amino acids that, if blocked by a drug docked onto the chromosome end at this location, may prevent cancerous cells from reproducing. The amino acids at this site are called the “TEL patch” and once modified, the end of the chromosome is unable to recruit the telomerase enzyme, which is necessary for growth of many cancerous cells.

Coauthors on the study include postdoctoral fellows, Jayakrishnan Nandakumar and Ina Weidenfeld; University of Colorado undergraduate student, Caitlin Bell; and Howard Hughes Medical Institute Senior Scientist, Arthur Zaug.

“This is an exciting scientific discovery that gives us a new way of looking at the problem of cancer. What is amazing is that changing a single amino acid in the TEL patch stops the growth of telomeres. We are a long way from a drug solution for cancer, but this discovery gives us a different, and hopefully more effective, target,” said Cech. He is the Director of the BioFrontiers Institute, a Howard Hughes Medical Investigator and winner of the 1989 Nobel Prize in Chemistry.

Telomeres have been studied since the 1970’s for their role in cancer. They are constructed of repetitive nucleotide sequences that sit at the ends of our chromosomes like the ribbon tails on a bow. This extra material protects the ends of the chromosomes from deteriorating, or fusing with neighboring chromosome ends. Telomeres are consumed during cell division and, over time, will become shorter and provide less cover for the chromosomes they are protecting. An enzyme called telomerase replenishes telomeres throughout their lifecycles.

Telomerase is the enzyme that keeps cells young. From stem cells to germ cells, telomerase helps cells continue to live and multiply. Too little telomerase produces diseases of bone marrow, lungs and skin. Too much telomerase results in cells that over proliferate and may become “immortal.” As these immortal cells continue to divide and replenish, they build cancerous tumors. Scientists estimate that telomerase activation is a contributor in up to 90 percent of human cancers.

To date, development of cancer therapies has focused on limiting the enzymatic action of telomerase to slow the growth of cancerous cells. With their latest discovery, Cech and Leinwand envision a cancer drug that would lock into the TEL patch at chromosome ends to keep telomerase from binding there. This approach of inhibiting the docking of telomerase may be the elegant solution to the complex problem of cancerous cells. Cech, a biochemist, and Leinwand, a biologist, joined forces to work on their latest solution.

“This work was really made possible by the fact that our labs are so close. My lab was able to provide the cell biology and understanding of genetics, and Tom’s lab allowed us to explore the biochemistry. We have a unique situation at BioFrontiers where labs and people comingle to make discoveries just like this,” said Leinwand. She is the Chief Scientific Officer of the BioFrontiers Institute and a professor of molecular, cellular and developmental biology.

Researchers at the University of Colorado have a significant history in developing marketable biotechnologies. Cech founded Ribozyme Pharmaceuticals, Inc. Leinwand co-founded Myogen with CU professor Michael Bristow, Hiberna and recently launched MyoKardia.

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