Graduate Students

Chris Smith (IQ Biology): Evolution Meeting

Anonymous — Wed, 26 Jun 2019 20:47:51 +0000

Chris Smith (IQ Biology): Evolution Meeting Anonymous (not verified) Wed, 06/26/2019 - 14:47

Chris Smith

I just got back from the Evolution Meeting in Providence and I’m full of information and ideas for research. I had the opportunity to reconnect with past colleagues and meet some new people. Other CU �鶹ӰԺ folks attended, including the labs of Dan Doak, Nancy Emery, Nolan Kane, Stacy Smith, and Scott Taylor (sorry if I missed any others).

Although most of the research represented at Evolution is empirical research on understanding and preserving biodiversity, many attendees were excited to discuss methods. In particular, producing large amounts of DNA sequencing data - both empirically, and using computer simulations - is no longer limiting in many cases. Therefore, the challenge of developing theory and methods for analyzing these data has received more attention in recent years.

Highlighting a couple of talks I thought were memorable: Paul Hohenlohe (U. Idaho) described the array of reduced representation sequencing approaches that are available and important trade-offs among them. Adam Jones (also U. Idaho) used simulations to see if and how pleiotropy and epistasis affect scans for loci involved in adaptation; he reported that pleiotropic effects don’t really affect outlier scans and that some important loci are still detected in the presence of genetic interactions. Zach Gompert (Utah State) presented a cool approach for quantifying fluctuating selection.

My presentation was part of the session on Population Genetics Theory, which is too broad of a name for the session because the talks were each focused specifically on inferring historical population sizes and admixture. Multiple speakers used ancient DNA to infer population history and used computer simulations to validate their approach. Other speakers, including myself, were trying to “break” commonly used tools that infer population history, to understand which parameters and data work best, or worst.

On a fun note, we got to see the “WaterFire” event in downtown Providence next to the convention center. This event is a big deal. There were thousands of attendees packed onto bridges and standing in the park along the river. Leading up to, and during the event, large amplifiers played music covering a range of- and alternating dissonantly between- intense classical music, tribal music, country music, and horns. At dusk, they lit small bonfires floating on the river. That’s it.

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Muscle-building proteins hold clues to ALS, muscle degeneration

Anonymous — Wed, 31 Oct 2018 06:00:00 +0000

Muscle-building proteins hold clues to ALS, muscle degeneration Anonymous (not verified) Wed, 10/31/2018 - 00:00

Lisa Marshall

Toxic protein assemblies, or "amyloids," long considered to be key drivers in many neuromuscular diseases, also play a beneficial role in the development of healthy muscle tissue, �鶹ӰԺ researchers have found.

"Ours is the first study to show that amyloid-like structures not only exist in healthy skeletal muscle during regeneration, but are likely important for its formation," said co-first author Thomas Vogler, an M.D./PhD candidate in the Department of Molecular, Cellular, and Developmental Biology (MCDB).

The surprising finding, published today in the journal Nature, sheds new light on the potential origins of a host of incurable disorders, ranging from amyotrophic lateral sclerosis (ALS) to inclusion body myopathy (which causes debilitating muscle degeneration) to certain forms of muscular dystrophy.

The researchers believe it could ultimately open new avenues for treating musculoskeletal diseases and also lend new understanding to related neurological disorders like Parkinson's and Alzheimer's disease, in which different amyloids play a role.

"Many of these degenerative diseases share a similar scenario in which they have these protein aggregates that accumulate in the cell and gum up the system," said co-first author Joshua Wheeler, also an M.D./PhD candidate in the Department of Biochemistry. "As these aggregates are beneficial for normal regeneration, our data suggest that the cell is just damaged and trying to repair itself."

For the study, Vogler and MCDB professor Brad Olwin, who study muscle generation, teamed up with Wheeler and Roy Parker, who study RNA, to investigate a protein called TDP-43.

TDP-43 has long been suspected to be a culprit in disease, having been found in the skeletal muscle of people with inclusion body myopathy and the neurons of people with ALS. But when the researchers closely examined muscle tissue growing in culture in the lab, they discovered clumps of TDP-43 were present not only in diseased tissue but also in healthy tissue.

"That was astounding," said Olwin. "These amyloid-like aggregates, which we thought were toxic, seemed to be a normal part of muscle formation, appearing at a certain time and then disappearing again once the muscle was formed."

Subsequent studies in muscle tissue growing in culture showed that when the gene that codes for TDP-43 was knocked out, muscles didn't grow. When the researchers looked at human tissue biopsied from healthy people whose muscles were regenerating, they found aggregates, or "myo-granules," of TDP-43. Further RNA-protein mapping analysis showed that the clusters - like shipping trucks traveling throughout the cell - appear to carry instructions for how to build contractile muscle fibers.

Wheeler and Vogler, both competitive runners and long-time friends, came up with the initial idea for the study while on a trail run. Wheeler says the data suggest that when healthy athletes push their muscles hard via things like marathons and ultramarathons, they are probably also forming amyloid-like clusters within their cells.

The key question remains: Why do most people quickly clear these proteins while others do not, with. the granules - like sugar cubes that won't dissolve - clustering together and causing disease?

"If they normally form and go away, something is making them dissolve," said Olwin. "Figuring out the mechanisms involved could potentially open a new avenue for treatments."

The team is also interested in exploring whether a similar process may occur in the brain after injury, kick-starting disease. And subsequent studies will go even further to identify what the protein clusters do.

"This is a great example of how collaboration across disciplines can lead to really important work," said Parker.

As participants in CU's Medical Science Training Program, which enables students to concurrently pursue a medical degree at the Anschutz Medical Campus and a PhD at CU �鶹ӰԺ, Wheeler and Vogler hope that someday the work they do in the lab will help the patients they see in the clinic.

"The holy grail of all this is to be able to treat devastating and incurable diseases like ALS and to develop therapeutic strategies to improve skeletal muscle and fitness," said Wheeler. "We are just opening the door on this."

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World Congress of Biomechanics – Dublin, Ireland

Anonymous — Wed, 24 Oct 2018 16:53:57 +0000

World Congress of Biomechanics – Dublin, Ireland Anonymous (not verified) Wed, 10/24/2018 - 10:53

Kristin Calahan

This summer, I had the opportunity to present my research at the 2018 World Congress of Biomechanics in Dublin, Ireland. As the premier meeting worldwide in the field of biomechanics, this was an incredible opportunity to network with scientists in this field, both within my subfield of biomechanics and far outside of it. I especially enjoyed this aspect of the conference because as an IQ Biology student I am intrigued by interdisciplinarity and the intersection of biology and mechanics at different length scales.

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Tom Cech leads RNA splicing dance

Anonymous — Fri, 20 Apr 2018 16:18:53 +0000

Tom Cech leads RNA splicing dance Anonymous (not verified) Fri, 04/20/2018 - 10:18

Cu �鶹ӰԺ Today

As part of BioFrontiers Institute Professor John Rinn’s biochemistry class, this week graduate students performed an RNA splicing interpretive dance on the west lawn of the Jennie Smoly Caruthers Biotech Building. CU Nobel Laureate and BioFrontiers Director Tom Cech (in the tie-dye T-shirt) played the starring role of the catalytic G, since he discovered and won the Nobel Prize for it. The balloons represent different parts of genes—purple are exons and green are introns.

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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 �鶹ӰԺ 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 CU �鶹ӰԺ 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 CU �鶹ӰԺ 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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Giancarlo Bruni named Gilliam fellow for minority mentorship

Anonymous — Mon, 14 Aug 2017 14:00:00 +0000

Giancarlo Bruni named Gilliam fellow for minority mentorship Anonymous (not verified) Mon, 08/14/2017 - 08:00

The Howard Hughes Medical Institute (HHMI) has announced today the 2017 Gilliam Fellowship awardees—exceptional doctoral students who have the potential to be leaders in their fields as well as the desire to advance diversity and inclusion in the sciences. CU �鶹ӰԺ Graduate Research Assistant Giancarlo Bruni is one of 39 recipients.

Bruni is currently pursuing a PhD in molecular, cellular, and developmental biology on the topic of bacterial electrophysiology. Prior to starting his graduate work at CU �鶹ӰԺ, he held research positions at Teleos Therapeutics and Massachusetts General Hospital.

Bruni also serves as a mentor to underrepresented groups through CU �鶹ӰԺ's SMART program, a 10-week summer session that helps level the playing field for underserved students who have not had the opportunity to participate in authentic research. He also worked with undergraduate students through the Colorado Advantage Program, encouraging them to pursue a graduate education by discussing his own experiences as a CU �鶹ӰԺ graduate student.

Read the HHMI news release published today.

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Curiosity killed the cat, but it may help you get the Nobel prize

Anonymous — Fri, 17 Mar 2017 06:00:00 +0000

Curiosity killed the cat, but it may help you get the Nobel prize Anonymous (not verified) Fri, 03/17/2017 - 00:00

BioFrontiers Institute

I don't feel frightened by not knowing things, by being lost in a mysterious universe without having any purpose - which is the way it really is so far as I can tell - it does not frighten me.

–Richard Feynman, The Pleasure of Finding Things Out

Doctoral students have a lot of time on their hands. It may appear otherwise, but the unstructured nature of a graduate student’s life lends itself to exploring seemingly endless plains of fascinating information. I am a Materials Science and Engineering Ph.D. student working on developing molecular tools like CRISPR (Clustered Regularly-Interspaced Short Palindromic Repeats used for editing DNA) to make microorganisms that can convert sugar into plastics. And somehow, on a snowy day in early January, I found myself going down a rabbit hole of attention-grabbing references that led from CRISPR to molybdenum.

Here are just a few fascinating facts I learned from this search: Did you know that molybdenum, occupying position 42 in the periodic table, has the sixth-highest melting point of any element? And that one of the world’s largest molybdenum mines – the Henderson Mine – is located near Leadville, Colorado, and adjoins a 10-mile railroad tunnel that goes under the Continental Divide? Or that molybdenum is an essential cofactor for nitrogen fixation in plants and arsenic detoxification in the liver? That there are species of archaea – some of the most ancient organisms on our planet – that can survive at pH < 0 (think battery acid) and reproduce at 250° F? And that some archaea have flat square-shaped cells? Oh, and that thing that initially began my search? There are now over 16 different subtypes of CRISPR systems.

So, how did I get from CRISPR to molybdenum mining? Mere curiosity. It may appear like a form of procrastination, but I prefer to think of it as an “idea treasure hunt.” In the process of mental exploration, one thought leads to another through association. Sometimes they flow in a linear pattern, other times they branch, splay and explode into thousands of new connections, forming intricate webs of facts and concepts in our brains. Occasionally an idea might wormhole its way to a distant node in the network, generating a surprising product – or even a revolutionary discovery. The mind theorists call this process the “promiscuous combination of ideas,” and it has led many scientists to come up with new theories and unexpected solutions.

Richard Feynman had the spark for his Nobel Prize-winning idea when he saw a student throw a plate across the cafeteria. Initially, he set out to solve a classical mechanics problem, but ended up in the quantum physics realm: the calculations of the wobbling speed and rotation of the plate transformed into a theory of how electron orbits move in relativity. Of course, that flying dish alone did not inspire the Nobel Prize theory. It involved connecting the dots from a giant constellation of concepts and theories in his mind. In the words of Feynman, “then there's the Dirac equation in electrodynamics. And then quantum electrodynamics. And before I knew it…the whole business that I got the Nobel Prize for came from that piddling around with the wobbling plate.”

One could argue that it was his deep understanding of physical principles and intense concentration that led Feynman to formulate the theory. I bet at least part of it was that Feynman was a man with insatiable curiosity; he was curious about how dreams work, how smart ants are, Japanese culture, or whether jelly can set at a low temperature if continuously stirred. When something grabbed his attention – like the wobbling plate – he chased after it, regardless of whether it was an elusive physics problem or something trivial he simply wanted to know more about. On his curiosity-fueled hunt for interesting things, he acquired a wealth of information and the ability to effectively process it, which enables one to draw surprising connections between distant ideas.

The information age has created a kind of “meta-mind” where people can easily share their ideas and together contribute to solving advanced problems. Most of the scientific discoveries today come not from individual researchers, but from the combined efforts of many people working in a field. For example, initial observations of the effects of CRISPR occurred in the dairy industry, where deliberate exposure to bacterial viruses (phages) was used to protect bacterial cultures against future phage infections¹. A computer search for similar sequences found fragments of phage DNA in the curious spacer-repeat CRISPR patterns, so it was proposed to be the bacterial “immune system”. Later, other researchers realized that CRISPRs could be expressed in different organisms and harnessed to target specified DNA sequences. Thus, CRISPR editing technology emerged from the combined efforts of many different labs and is now being proposed for applications like modifying human embryos – a prospect almost as far removed from its original use for making yogurt as it is from molybdenum mining.

I doubt that any scientist could have single-handedly figured out the application of CRISPR technology for gene editing purposes. Advancements like that take the combinatorial powers of the collective scientific mind. However, smaller discoveries are happening in labs every day, and they also require connecting the dots between quite distant concepts. So, next time you catch yourself procrastinating by reading seemingly unrelated articles on the internet, or by watching ants going about their business, or throwing a Frisbee (while trying to calculate its rotation speed in the air) – don’t be so hard on yourself. After all, you may just stumble upon your Nobel Prize idea.

¹If you are curious, this source provides a great timeline of CRISPR discovery and development.

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Continuing a bioscience legacy at CU �鶹ӰԺ

Anonymous — Mon, 01 Aug 2016 06:00:00 +0000

Continuing a bioscience legacy at CU �鶹ӰԺ Anonymous (not verified) Mon, 08/01/2016 - 00:00

BioFrontiers

John Milligan spent two years at the �鶹ӰԺ during his graduate studies in the mid-1980’s. He helped to move his mentor, Dr. Olke Uhlenbeck, in a U-Haul truck across the Great Plains to the Rockies. Uhlenbeck was recruited from the University of Illinois in 1986 to head CU �鶹ӰԺ’s biochemistry division, which included many of CU’s research stars.

Five years before, in 1980, Professor Marvin Caruthers and seven other research scientists founded Amgen, a biotechnology company that now has approximately 18,000 employees worldwide. Four years later CU’s Tom Cech would win the 1989 Nobel Prize in chemistry.

Milligan is now the president and chief operating officer of Foster City, California-based Gilead Sciences, Inc., a biopharmaceutical company focused on advancing the care of patients suffering from life-threatening diseases worldwide. Milligan spent two years of his PhD studies at CU �鶹ӰԺ in Uhlenbeck’s lab after it moved from the University of Illinois, and then later started at the then-developing Gilead Sciences as employee #32.

“Because I came to CU in the middle of my graduate work, I enjoyed the best of both Colorado and Illinois,” says Milligan, who eventually returned to the University of Illinois to finish his PhD. “In Colorado I loved that we were aligned with biologists and that there was a close community of people working on RNA.”

To honor the mentorship Milligan received from Uhlenbeck, he recently donated $1 million to establish the Olke C. Uhlenbeck Endowed Graduate Fund for students participating in the BioFrontiers Interdisciplinary Quantitative Biology, or IQ Biology, PhD program. Milligan liked that the program focuses on exposing graduate students to other aspects of working in biological sciences, from writing computer code and learning applied math to professional development: all skills important to any career, whether in industry or academia.

“I really value the time I spent at CU �鶹ӰԺ with Olke,” says Milligan. “I appreciate the conversations we had as I developed into a scientist. He also taught me to be leader by showing me what it meant to be engaged in research and intellectually curious.”

The BioFrontiers Institute’s Director, Tom Cech, now a distinguished professor in chemistry and biochemistry at CU �鶹ӰԺ, will participate in choosing the first Uhlenbeck Fellow from the incoming class of IQ Biology students this fall.

“I love that John is supporting graduate education. It’s the right thing to do at the right time,” says Uhlenbeck, adding, “I feel a little strange to have something named after me…but I’ll get over it.”

Milligan and Uhlenbeck arrived at CU �鶹ӰԺ during a period of rapid growth in its reputation as a ribonucleic acid (RNA) research powerhouse. Uhlenbeck agreed to come to �鶹ӰԺ, with the condition that CU’s various RNA research groups meet together regularly to share information and collaborate on projects.

These “RNA Clubs” eventually grew to more than 100 faculty, students and industry scientists sharing what they were discovering about RNA. The interactive meetings helped CU �鶹ӰԺ to grow in its RNA research dominance, which supported the launch of many �鶹ӰԺ biotechnology startups, including Ribozyme Pharmaceuticals Inc. and NeXstar Pharmaceuticals, Inc. The RNA Club is still active at CU, more than 30 years later.

Despite the often-bleak news graduate students face about the loss of federal funding and academic jobs, Uhlenbeck has a positive outlook about the opportunities graduate students now have. Over his academic career he mentored more than 40 graduate students, including Milligan.

He feels that students now have more choices for career paths and are not limited to life in academia. �鶹ӰԺ a third of Uhlenbeck’s former students now hold academic jobs, but the rest have varied careers ranging from a patent attorney to running a lab for testing biological samples from hospitals.

“My best advice to graduate students right now would be to keep an open mind,” says Uhlenbeck. “I think students are sometimes discouraged when they believe they have to become professors. The world is so much bigger now and they may find they are better suited for research in industry, medicine or law. You need to be intellectually agile to be able to know how to search for something when you don’t know everything.”

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Bioinformatics answers questions

Anonymous — Fri, 05 Jun 2015 06:00:00 +0000

Bioinformatics answers questions Anonymous (not verified) Fri, 06/05/2015 - 00:00

BioFrontiers

Bioinformatics answers questions of cancer and career path

Phil Richardson, an author on a paper recently published in Nature, developed a love for bioinformatics in BioFrontiers' Robin Dowell's lab. His next move: pursuing a graduate degree in medical genomics.

At some point in school, we were taught that humans are a diploid species, made of cells with two sets of chromosomes – one set contributed by each parent. This idea neatly packaged the way we believed cells carried on with dividing themselves and creating more cells, but it isn’t the only way. Polyploidy occurs when cells have more than two complete sets of chromosomes. Polyploids are common: Plants, some fish and amphibians are polyploid. Aneuploidy is yet another chromosomal mix – one where there is an abnormal number of chromosomes in a cell due to extra or missing chromosomes. While being diploid looks much simpler on paper, recent research points to the chromosomal flexibility of the ancestors of many diploid species, because as it turns out, polyploidy and aneuploidy appear to be pretty helpful in smoothing out the evolutionary ride.

In a recent paper in Nature, BioFrontiers Institute faculty member, Robin Dowell, an assistant professor of Molecular, Cellular and Developmental Biology, describes the influence that polyploidy has on accelerating evolutionary adaptation. By studying Saccharomyces cerevisiae, a helpful species of yeast well-known in winemaking, baking and beer brewing, Dowell was able to show that many individual strains can switch between polyploidy and aneuploidy, and they do so to adapt to evolutionary and environmental changes.

“To me, the interesting thing that came out of this study is that being aneuploid can help polyploids,” says Dowell. “When faced with a lot of evolutionary or environmental pressure, polyploid cells can switch quickly to being aneuploid. It seems like it becomes a short-term solution for these cells.”

Dowell’s lab is, in part, focused on studying how chromosomes influence adaptation and how these adaptations affect cellular processes. These processes are poorly studied because genetic data creates huge datasets and many labs lack the computational tools and abilities to dig through them. Dowell’s lab, in the Jennie Smoly Caruthers biotechnology building, blends a biological wet lab with a computational dry lab resulting in research that has the capability to look deeply at bioinformatics.

Phil Richmond is part of Dowell’s lab and a co-author on the Nature paper. He did much of the groundwork for this research as an undergraduate in the Department of Molecular, Cellular and Developmental Biology at CU-�鶹ӰԺ. His job was to comb through the data of 130 genome-sequenced strains, narrowing the dataset to 78 that were of acceptable quality to study.

“One of my biggest contributions on this project was benchmarking a way to track mutations in the genes,” says Richmond. “Everything was built for humans with a diploid assumption and the current tools couldn’t find mutations in polyploid yeast. This was my first really cool experience in digging into genomics.”

Polyploidy and aneuploidy become interesting study subjects when it comes to cancer. From a cancer standpoint, polyploidy is a mistake in replication of chromosomes, and the odds of a polyploid cell becoming cancerous are increased. Some cancers appear to start when the cell divides and extra chromosomes go into one cell instead of splitting evenly between two. As this happens over and over, a cell can quickly become what scientists call “self-interested” and become a soft tumor.

Genetic sequencing is showing promise as a powerful tool for learning about different types of cancers. Richmond started at CU-�鶹ӰԺ as a pre-medical student and quickly fell in love with biology. Dowell hired him into her lab as a sophomore where he filed papers and washed glassware, but it wasn’t long before Dowell recruited him for a programming project.

“I had never programmed anything,” says Richmond. “But since then, the number of tools available and people that are interested in bioinformatics has grown exponentially, and I’ve been riding that wave ever since. I’m no expert in any of the fields I’ve collaborated in, but my bioinformatics skillset has allowed me to be useful in a lot of different projects. I chose a path that will just keep growing.”

Richmond would love to see cancerous tumors undergo genetic sequencing so that doctors will know what they are treating and how best to treat it. He believes that, although sequencing costs are still relatively high, it might be more cost effective in the long run to sequence a tumor rather than have a patient take the wrong drugs without results.

“This study really brought out one big outlying question,” says Richmond. “When a tumor becomes polyploid, is it the result of some random system, or is it providing an advantage to the cell? We’ve shown that yeast—a eukaryote—is able to adapt faster in the polyploid state, so what we learned is helping us to think of the chromosomal copy number profile in cancer as more of an evolutionary advantage rather than the result of a chaotic and unstable system operating in the cell. This may change the way we approach the treatment of this disease in the future.”

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