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IQ Biology Blog: Computing Machinery and Mouse Genomes

IQ Biology Blog: My experience with Evolution

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IQ Biology Blog: My experience with Evolution

Anonymous — Tue, 30 Aug 2016 06:00:00 +0000

IQ Biology Blog: My experience with Evolution Anonymous (not verified) Tue, 08/30/2016 - 00:00

BioFrontiers

by April Goebl

Attending Evolution, the premier international conference for evolutionary biology, had a big influence on my recently spawned, yet still vague, choice to pursue a career in evolutionary biology. Held in Austin, Texas this year and the largest conference in its field, Evolution is a joint event for three major societies: the American Society of Naturalists, the Society for the Study of Evolution, and the Society of Systematic Biologists.

By observing well-seasoned Evolution attendees, I noted their strategy for making the most of the busy conference: Attend talks on emerging methods, and spend time re-connecting with old lab mates and collaborators. For those transitioning from undergraduate, this conference was an optimal space to explore the breadth of current evolutionary biology research and to casually meet and chat with potential graduate advisors.

For me (someone recently starting on their PhD journey with broad interests in ecology, evolution and environmental biology) attending this conference felt like a well-timed bonus. I was able to attend talks and posters ranging from genomics, population genetics theory and ecological genetics to speciation and adaptation, biogeography, and conservation biology.

While this breadth of selection was nothing short of overwhelming for someone that struggles with indecision, the payoff of defining where my interests lie was well worth it. The challenge of navigating which talks to attend and how to traverse the conference center in time to make my next session of interest, was balanced by the reward of gaining insight into how to appropriately ask questions in this field and how to try to answer them.

IQ Biology Blog: Computing Machinery and Mouse Genomes

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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.

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Science is Hard

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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.

IQ Biology Program Wins IGERT

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IQ Biology Blog: On the leading edge

Anonymous — Fri, 06 Sep 2013 06:00:00 +0000

IQ Biology Blog: On the leading edge Anonymous (not verified) Fri, 09/06/2013 - 00:00

BioFrontiers

Studying Quantitative Genomics in Italy

By: Nora Connor

I returned this past weekend from a conference and workshop called Quantitative Laws of Genome Evolution in Lake Como, Italy. An Italian physicist named Marco Lagomarsino created the conference, which brought together an interdisciplinary group of statistical physicists, biophysicists, chemists and biologists to talk about genomics.

My personal research interests lie in understanding horizontal gene transfer in bacteria and its relationship to the development of antibiotic resistance. I talked with many attendees – who were mostly European grad students and postdocs – about my own research on bacterial genome size. But to really understand the talks and lectures, I needed a solid grounding in a broad range of fields.

In that regard, I couldn’t have been better prepared for this conference. IQBiology gave me the background I needed to understand and appreciate almost every seminar for ten jam-packed days. I had done a project on protein folding for the IQBiology Foundations course, which enabled me to talk with a Danish researcher about his work on metabolic networks. I understood the talks about evolutionary processes in software packages because of my advisor Aaron Clauset’s research about macroevolution – and I spoke with those physicists about their work, how it relates to genetic evolution, and future collaborations. I could converse with biophysicists studying biofilm growth because I had done wet lab work with Bacillus subtilis and watched (and smelled!) my colonies grow wrinkly biofilms. And I was able to engage with researchers studying nucleosome methylation and its potential role in tumor-cell replication, because I understood the nucleosome’s role in transcriptional regulation, thanks to my Statistical Genomics class with Robin Dowell and Manuel Lladser.


*Nora enjoyed this view on her daily conference commute.*

Many of the senior scientists at the conference are interested in the next frontier in biology. They asserted that the years 1990-2010 were the era of genomics, and the years 2010-2020 will be the years of “pangenomics.” The pangenome describes the whole universe of possible genes that might be available to an organism, and thus the possible functions or traits that an organism might be able to adopt. In bacteria, these can be acquired via horizontal gene transfer or viral transduction. The incredible conclusion thus far is that the entire prokaryotic pangenome may include only one million genes. Sure, that may sound like a lot of genes, but remember that bacteria and archaea have been evolving for 3.5 billion years! This area is just developing, but there was a lot of enthusiasm about how ecology may constrain functional radiations, and the implications for cell immunity – for instance, whether individual cells can combat cancerous mutations or viral invasions.

Even though many of the physicists and chemists at the conference were engaged in theoretical research, most of them saw direct application of their work to medical and societal problems. The talks alternated between models of so-called “fitness flux”, to the philosophy of the origin of life, to new approaches to combating HIV and antibiotic resistance. This is the frontier of science, being navigated by interdisciplinary researchers from all over the world. I am incredibly grateful to the IQBiology program for my interdisciplinary education to allow me to be on the leading edge of the cutting-edge.

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IQ Biology Blog: Understanding RNA

Anonymous — Tue, 16 Jul 2013 06:00:00 +0000

IQ Biology Blog: Understanding RNA Anonymous (not verified) Tue, 07/16/2013 - 00:00

Aaron Wacholder

The newly constructed structure in the National Botanical Gardens in Ireland, meant to symbolize the flow of information from DNA to RNA and proteins, contains a representation of the DNA double helix, a ribosome, and thehammerhead ribozyme. Sculptures of the DNA helix have been constructed all over the world; indeed, wandering through Trinity College Dublin a few miles from the gardens I found a double helix sculpture that had been unveiled by James Watson in 2003. Though much rarer, there's at least one previous sculpture of a ribosome, located at Cold Spring Harbor. I can say after some searching, however, that I believe the Ireland National Botanical Gardens contains the first example of a sculpture of catalytic RNA. Ribozymes, hugely important to our understanding of the place of RNA in the universe, had been discovered by Nobel Laureate, BioFrontiers Institute Director, and IQ Biology Foundations class instructor Thomas Cech in 1981, but this appears to be its first manifestation in sculpted form.

My opportunity to attend the unveiling of the scultpure was mostly the result of luck. The sculptor, Charles Jenks, requested a 3D model of the hammerhead ribozyme on which to base his sculpture, and molecular biologist John Atkins, who organized the event asked Tom Cech if he could provide one. Dr. Cech decided it would be a good opportunity for our Foundations class to show off our artistic talents as well as our understanding of RNA structure, a major subject of the course. We divided outselves into teams and competed to see which of us could produce the most accurate representation, with the reward being a trip to Ireland. Building an accurate 3D model from the computer representation in Pymol (a program for molecule visualization) requires spatial skills that I, leaning more towards the theoretical side of biology, do not have. Fortunately, my teammate Zachary Dunlap was much more skilled than myself in this regard, and due to his talent and effort, our final model was deemed the most accurate. Zach and I were invited to attend the unveiling of the statue.

**An early, only moderately succesful attempt at a hammerhead ribozyme model. The one we actually sent was better. I haven't been able to locate it.**

James Watson, who (as you probably know) was one of the discoverers of the structure of DNA, spoke at the unveiling. A major theme of his speech, and the sculpture itself, was the complexity of RNA. Watson said one line which I've thought about quite a bit in the time since (I didn't immediately recognize its significance, so this is my paraphrase): DNA is as much as most people can understand. Understanding RNA makes someone a scientist.

***James Watson, co-discoverer of the double helix, speaking in front of the ribozyme***

The public has some understanding and appreciation of DNA, but comprehending RNA, and what it does and means, is much harder, in part due to its many biological roles. That's why there are many sculptures of the DNA double helix in the world, but so few of RNA, and why the exhibition in the Botanical Gardens is novel and interesting. This sculpture, comissioned in order to promote understanding of science among the young, includes RNA as well as DNA so as to educate on the many new discoveries involving RNA in the last 30 years. The discovery of ribozymes established that RNA was more than its role in the Central Dogma as passive messenger, transmitting genetic information from DNA to be translated into proteins, the catalytic units of the cell. Rather, RNA is itself an active player: the hammerhead ribozyme can cleave RNA without protein enzymes. Since the discovery of catalytic RNA, we have learned more and more about how RNA is involved in a multitude of functions: information, structure, regulation, catalysis. The multifaceted nature of the molecule is emphasized in the sculpture. Three forms of RNA are placed on top of the ribozyme, over the words: The First Multitasker. It is an appropriate term.

**This is supposed to look like a question mark, to symbolize all we still don't know about RNA.**

The structure of DNA is aesthetically pleasing, and its discovery a great accomplishment. But I think it was the right decision to put an example of catalytic RNA as the focus of the exhibit, the first structure a person will see walking down the path towards the sculpture. The discovery of Watson and Crick represented the accomplishment of a great scientific goal that had been established as soon as it was understood that DNA was the genetic material. But Cech's discovery is an example of something that, to me, is an even more exciting appeal of science: the potential for an unexpected result to overturn previous knowledge, to add complexity to our old understanding of life and open the path to whole new areas of research, previously unimagined.

***The familiar DNA double helix, with ribosome in the background***

Aaron Wacholder is beginning his second year in the IQ Biology program. He is pursuing a PhD in Ecology and Evolutionary Biology.

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IQ Bio Blog: Interdisciplinarity on Steroids

Anonymous — Wed, 06 Feb 2013 07:00:00 +0000

IQ Bio Blog: Interdisciplinarity on Steroids Anonymous (not verified) Wed, 02/06/2013 - 00:00

BioFrontiers

IQ Bio Blog: Interdisciplinarity on Steroids

by: Ryan Langendorf

At my last mentoring committee meeting, after discussing the tug-of-war that the Environmental Studies and IQ Biology programs have been playing with my schedule, Dr. Brett Melbourne paused and quietly commented that my life is “interdisciplinarity on steroids!” We all laughed, but sometimes I lose sight of how many worlds I inhabit. Most graduate students are like horses at a racetrack: blinders on, charging ahead singularly. I am lucky enough to have found myself in not one, but two programs that span disciplines in meaningful ways.

So what is a day of interdisciplinarity on steroids like? Well, imagine being crowded into a small, overly warm basement classroom debating the role scientists ought to play in society and politics with perspectives ranging from philosophical justifications to legislative ideologies to scientific uncertainty. Then, the clock strikes 1:30. You grab your things, dash out of the room, sprint up the stairs, tear across the quad, zigzag past oncoming traffic, catch the bus pulling out, stampede over to the new biotech building on east campus, run up the stairs, yank open the door, slide next to your classmates and start in on a presentation explaining how Fourier transforms are used in x-ray crystallography and electron microscopy. Just another Tuesday afternoon.

Definitely hyperbolic, but that cross-campus dash I made last semester happened not only every Tuesday but almost daily as I bumped into people or switched homework gears or met up with PIs and students for research meetings. I would never trade my life at CU for a more traditional graduate career, but making connections between the disparate areas of my life can be a career on its own. Sometimes I like to imagine people carrying spools of string everywhere they go. I’m not sure how my path through life would appear to an eagle passing by, but I like to imagine it would zigzag around the campus connecting seemingly unrelated buildings in interesting ways.

"I have come to believe that scientists are truly today's superheroes. And just like any good superheroes, tackling the greatest of obstacles requires teamwork."

I spent this past summer in the Nevada desert trapping and tracking Microdipodops pallidus (the adorable and locally at-risk pale kangaroo mouse which tries very hard to live up to its name) and figuring out where and what graduate school would be for me. My advisor, Dr. Dan Doak, offered the more traditional ecology and evolutionary biology department as an option and it weighed heavily on me.

I have always sought means to integrate far-ranging disciplines like math, sociology, public policy, and computer science into my research, but have always done so from a more traditional perch. When I visited schools last spring I made sure to ask every student I encountered how often they interacted with people from different disciplines and with different perspectives. So few seemed to understand why I was even asking, as if all the answers lay close at hand. Here, in Boulder, I am surrounded by people who see differences as the strongest reason to collaborate, and it is inspiring.

I have come to believe that scientists are truly today’s superheroes. We may not have omnipotent suits in our closets like Tony Stark or be able to read minds like Charles Xavier, but when it comes to saving the world, to believing no disease incurable, no planet too far away, no species too unimportant, the scientific community is a pretty heroic bunch. And just like any good superheroes, tackling the greatest of obstacles requires teamwork.

The inspirational Nigerian author Chimamanda Adichie speaks of “the danger of a single story”. By this she means the threat of people who see the world through only one perspective, who approach life singularly. This danger seems as real as ever for scientists, and I hope more students find it within themselves to challenge disciplinary thinking as profoundly and meaningfully as my classmates and colleagues in Boulder do every day.

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