I recently listened to the Systems Biology Nature podcast.

Systems biology is mathematical modeling of biological systems (even at the molecular/gene level) with the intention of reproducing emergent properties in complex living systems. These mathematical systems could  combine everything from gene regulatory networks to crazy metabolic networks into one glorious approximated abomination of biology. This research could lead to at least two great things:

1. Spore 2 (check out local guest blogger Kate’s Spore creature gallery)
2. Accurate evolution simulations, ie. new opportunities for creationist bashing

Systems biology is a perfect example of a new multidisciplinary field. It combines the work of mathematicians, computer scientists, physicists, bioinformaticians, biochemists, molecular biologists, cell biologists, and geneticists. Even a philosophy major could probably slip into the team undetected for a little while!

As grad school selection approaches and life decisions loom above like an angry sun, it really begs the question: Should one be specializing or diversifying ones skill set?

Sure, you could diversify (your bonds) and learn about computer science and physics like me, or you could specialize the old fashion way and join some miraculous science collaboration dream team to work on cutting edge science.

The case for diversifying is argued nicely in a PLoS essay entitled: “Antedisciplinary Science“. (Hat tip!)

It turns out that antedisciplinary science aligns nicely with the ideal Jacks of Science “Jack of all trades” blogging philosophy:

Perhaps the whole idea of interdisciplinary science is the wrong way to look at what we want to encourage. What we really mean is “antedisciplinary” science—the science that precedes the organization of new disciplines, the Wild West frontier stage that comes before the law arrives.

The essay was written by a computational biologist and the topic really hits home for me. By next April I’ll have graduated with equal amounts of physics and computer science credits thanks to University of Waterloo’s free-spirited computational science program. But I’m kinda doomed. I don’t have the expected skillset of a physics major or of a computer science major if I choose to go to grad school for either.

I should have specialized in something!

Why am I currently researching computational chemistry!?

Why do I plan to study polymer physics next term!?

Who am I!?

What’s the best way to bypass expensive conference fees as an undergrad? Volunteering of course!

This year I’m volunteering at the ISMB 2008 conference in Toronto, which, for a minor time commitment, entitles me to hear fascinating presentations on all aspects of computational biology and bioinformatics. One of these was a tutorial on ncRNA (noncoding RNA) gene finding, given by Jan Gorodkin and Ivo Hofacker.

First, a quick intro.  Most of what we know about the genome deals with coding sequence:

• DNA that’s transcribed into messenger RNA (mRNA) 
• mRNA that’s translated into proteins

But only 1.3-1.6% of the (human) genome codes for protein!  The rest, despite the popular misconception, is not “junk DNA“.  DNA and the transcribed non protein coding RNA have many functions, a few of which we know about [PDF].  The recent ENCODE pilot project estimated that as much as 97% of the human genome is transcribed into mRNA at some point. But what does it do?

There are many different classes of ncRNAs.  First, you’ve got transfer RNA (tRNA) and ribosomes, which have functions in translation of mRNA to peptides.

Another type of ncRNA are MicroRNA, or miRNA.  These are short sequences of RNA that are complementary to (protein coding) mRNA.  They act as downregulators (suppressors) of genes, by attaching to the mRNA and getting in the way of the translational machinery.

Discovering ncRNA genes can be tricky! This is mostly due to the fact that ncRNA function is in many cases tied inextricably to the structure of the transcribed RNA.  RNA, being single stranded, can double up on itself and form loops and helixes (as pictured below).  These crazy loops are called the secondary structure. The secondary structure of RNA is what results from the first pass of folding, and serves as a simplified (but useful) model for the 3D structure of the RNA.

Because the secondary structure results from the pairing of bases, any of the so-called canonical base pairs (C-G, A-U, U-G, and the reverse of all three) can occur.  Mutations can occur that change the sequence, but keep the bases paired in the same way, leading to structures that are the same, but with sequences that are very different.  

However, a single nucleotide that no longer base pairs the same way can produce a completely different secondary structure.  In the world of bioinformatics this can make it difficult for computer algorithms relying only on nucleotide data to align sequences that are too dissimilar.  There are algorithms that can align sequences based on conserved structure, but they are computationally expensive both in terms of memory and CPU time.

That said, sometimes alignment based only on sequence are good enough.  Sequence alignment tools are fairly common, and alignment data across many species is available for downloading.  Algorithms can use these alignments to discover the genomic locations of new ncRNA genes.  Because the sequence (well, structure) of an ncRNA gene will stand firm while the sequence around it mutates, functional genes will stand out as regions with high conservation across an evolutionary tree.

The alignment of multiple sequences is used in a few different ways to discover ncRNA genes.  Some of them use the known evolutionary tree in a probabilistic way (how likely is it that this nucleotide mutated from A to U?  What if it’s part of a base pair?) to try and find a consensus structure.  Others calculate the stability of the stuctures formed.  Sequences with the most stable structures tend to be functional.  There are algorithms that combine the two approaches.

The sets ncRNA genes predicted by these different matches have little overlap.  This may be due to lots of false positives being predicted, or it may be because certain approaches are more likely to find ncRNA genes of certain types or with certain properties.  Improvement of these methods, as well as secondary-structure based sequence alignment and prediction of RNA structure and function, remain areas of ongoing research.  It’s clear that we’ve already begun to crack the genetic code.

The secondary structure of ribosomal RNA from E. coli.

But as my first order of business, I’d like to demolish some zoological misconceptions I commonly come across. I hate zoological misconceptions! Let’s begin:

1. Assuming you live in the New World, honey bees are not your friends. Nor are they friends with your true bee friends, the native bumblebees. Honey bees were introduced to the Americas by European apiculturalists, making them an ALIEN/INVASIVE species. So, it shouldn’t be any wonder that they are “declining“, given that they didn’t belong here in the first place (OH SNAP).

2. Daddy Long-Legs are not spiders, nor are they poisonous. They are harvestmen. Also, check out the weird pro-harvestmen science bias in the Wikipedia article:

Because they are an ubiquitous order, but species are often restricted to small regions due to their low dispersal rate^{[citation needed]}, they are good models for biogeographic studies^{[dubious – discuss]}.

Indeed! Dubious!

3. Polar bears are not a distinct biologically species, separate from grizzly bears and brown bears (which themselves are not biologically distinct). In other words, polar bears, grizzly bears and brown bears are in fact all the same (biological) species, and hybridization is possible!

4. Monkeys and Apes are different things! Chimpanzees, Bonobos, Gorillas, Orangutans, Gibbons and Humans are apes. Apes, I say! Monkeys are things like Tarmarins, Capuchins, Owl Monkeys (above), etc. So, next time your esteemed associates say “Humans are descended from monkeys!” you can say “That statement is incorrect, associates! They are descended from, and still are, apes!”.

5. Killer whales are oceanic dolphins, not whales. Similarly, Koala bears are not bears.

Do you feel informed? I have many more such facts, stay tuned!

Last year I did a co-op placement working on some medical imaging software. Looking back, I definitely needed more C++ knowledge, but I ended up walking away with from the job with many crucial linux development, programming, and pasta boiling skills.

Wait, pasta boiling?

You heard me correctly. Here’s a short video of some zitoni we imaged in real-time using the software I was working on. Note that the quality is butchered because it was originally captured in an unusual resolution.

You can see me frantically moving the slice plane and rotating this view in 3D. This branching pasta creation was made to to be similar to the branching vasculature found in the body so we could easily test our software and catheter tracking.

I made this fantastic creation by first obtaining zitoni, a long tubular pasta, from Masellis Supermarket in Toronto (it’s a great Italian market). Then I boiled the pasta until al dente in water and Gadovist, which is a commonly used contrast agent for MRI. I carefully sliced holes and wrapped the pasta joints in Saran Wrap. I then suspended the pasta abomination in Agar. All credit goes to my graduate student supervisor Kevan Anderson who came up with the idea.

Near the end of the video, in the cross sectional slice of the pasta tube, you can see some horrible black mess within the pasta. That’s an air bubble due to my sloppy joint wrapping. It shows up as black, an area of zero signal, because air has no magnetic properties. 

In the making of the pasta phantom I used enough contrast agent to make the pasta appear gray under MR, but what if I wanted more precision to have the pasta appear identical to human tissue? 

New research in Nature last week outlined the fabrication of magnetic particles for use as contrast agents in MRI. By engineering your own magnetic particles you could tailor their characteristic spectral signals to show up exactly how you’d like them to. The precise control of contrast with magnetic particles has great implications in imaging from cell tracking, to micro fluidics, to realistic pasta arteries. 

However, it is really moral to keep animals locked in our houses, mostly for our own enjoyment? Furthermore, is it moral to genetically alter (i.e. breed) animals to look “cute” or “handsome”, even if that means creating in serious health risks for the animals?

Based on the picture above, I’m inclined to say that the moral risks are well-worth the hilarious pet-wig payoffs. For the sake of argument, here’s a run-though of the various moral justifications I’ve heard from pet-owners, along with my zoological retorts:

1. “Pets live much better/more comfortable/longer lives in human homes than they would in the wild.”

This one is tough to defend. It rests upon the anthrocentric idea that humans, being all-mighty, must know what’s best for animals and how to give them the most fulfilling lives possible. But how can you ever know whether or your dog is truly better off in your house versus the lush woods?

2. “Dogs and cats have been selectively bred to enjoy the company of humans. My dog loves it at home!”

The problem with this that is assumes that the behavior the animal has been selected to express (amicability to humans) is truly reflective of the animals thoughts/”feelings” (i.e. that they really do enjoy the company of humans, rather than simply behave that way).

3. “Working animals, such as seeing-eye dogs, increase the owner’s quality of life dramatically.”

This is probably true. However, it doesn’t change the fact that the animal is born into a life of servitude.

4. “It has been suggested that dogs may have domesticated themselves. They’ve got themselves into this mess, they can get themselves out.”

I haven’t thought of a clever response to this yet. I was thinking about using “Its only a theory!”, but we all know where that leads.

So, it seems that the keeping of animals as pets is, at least in some ways, difficult to defend from a moral standpoint. In spite of all my zoological musings, Chris sent me the following video that blew my arguments to smitherines:

Did you know that scientists have created artificial DNA? Just for the record, that’s only one step away from inserting the DNA into a cell and bringing it to life. However, this area of research is still in it’s infancy so we won’t have any soulless synthetic human puppets for very much longer a long time.

Most recently, the synthesis of a meager 500,000 base pair bacterial genome was explained in detail by the researchers at the J. Craig Venter Institute. The size of the bacterial genome pales in comparison to our hulking 3 billion base pair human genome of champions but it’s a step in the right direction. Naturally, stepping in said direction is a cause for bioethical concern but I’m more interested in the new possibilities for biocrime!

It has been 20 years since DNA evidence was first admitted in court which lead to a death sentence. Similarly, it has been a recurring plot device for television crime drama for just as long. Being exposed to such shows, today’s criminals know better than to leave saliva, blood, or semen at the scene of a crime if they can help it. Although, with the advent of synthetic DNA, bodily fluids may be making an unexpected comeback…

Everyone knows that planting DNA evidence like hair or fingernail clippings is a straight forward way to frame someone for a crime they didn’t commit, but let me walk you through a more intriguing scenario:

1. Almost half a billion DNA profiles of offenders are contained in the FBI’s CODIS National DNA Index.
2. A crooked cop or hacker mastermind leaks criminal DNA profiles to the internet. 
3. A regular joe (RJ) obtains a DNA profile of regular criminal (RC) on parole in his area.
4. RJ has DNA synthesized en masse and inserted into cells by a private lab.
5. RJ commits his crime of choice, stealing a rhubarb pie from a windowsill, without leaving any trace of his own DNA (easier said than done).
6. The forged DNA is left at the scene of the crime.
7. Forensic scientists find a direct DNA match with RC using the CODIS National DNA Index.
8. Assuming RC has no significant alibi, he is considered a repeat offender and found guilty of grand theft pastry.
9. RJ, pretty hungry at this point, consumes pie and sends an anonymous thank-you card to J. Craig Venter Institute without ever having made contact with RC.

This scenario may seem far fetched but it’s undeniable that the validity of DNA evidence relies on the fact that people assume DNA cannot be tampered with. Much like the questionable admissibility of digital photography and digital video in court due to computer forgery, DNA evidence will one day be under high scrutiny. 

Computer simulations of evolution offer an excellent solution to this problem. Using these simulations, students and scientists can explore the process of evolution and get (in some cases highly visual) results in a matter of minutes. Luckily, thanks to intrepid biologist/programmers, many of these sexy in silico simulations of evolution are now freely available for download! Here are a few, at a glance:

Breve Creatures

Gene Pool

Java Evolution Simulator

Java Biomorph (Java implementation of the Dawkins Biomorph program)

Mushroom Life

(OK, its not a true evolution simulator, but I have a soft spot for Conway’s Game of Life. And mushrooms.)

See also:

Dr. Saul’s Evolution Lab
Evorunners
Flow in games
Maxis 1990 computer game Simlife
Discussion of the validity of computer simulation to provide evidence for evolution.

Jacks of Science is a bit of an experiment.

I hypothesized that the site would become a flourishing group science blog as far back as 2006.

To observe this desired blog state I devised a simple theory. I would mix a solution from a staff of student bloggers in different fields such as Physics, Biology, Geology, and Chemistry.

Would I be able to find reactants that formed a homogeneous mixture or a highly reactive substance on the brink of explosion?! Even if I found writers that worked coherently together, would I continue to get decent results over time? 

I figured that the greatness of Jacks of Science would be directly correlated with post diversity. Many authors would lead to diversity in post subject matter, writing style, humor, complexity, geekiness, and length. However, in theory, things are much different than in experiment. As you may have noticed, this diversity of authors ended up just being a diverse range of posts authored by me. I didn’t follow through on my original plan of finding other writers since I was busy trying to become a better blogger myself.

The original intention of the site has been lost but, 102 posts later, as my domain renewal date draws nearer, you’re looking at the results of the Jacks of Science experiment. Full of random art doodled on my class notes (which now includes my 1st and 2nd year!), to pro-piracy open science discussion, to science DJ mixes, to my most popular article: Science Valentines.

So I’m trying to draw some conclusions about the data so far. As far as the traffic indicates the site is growing in popularity but I’m just not sure if things are working out. Blogging is a lot of fun, but the Jacks of Science initiative, as originally imagined, has been stagnant for some time. It doesn’t seem to be going anywhere for a variety of reasons off the top of my head.

• No clear audience that I’m writing for!
• No incentive for new writers to be part of the site!
• I can only post once a week by myself (quality over quantity)!
• Science is boring (and thus cannot reach a wide enough audience)!
• My single column blog theme is too narrow!

You may have heard of Craig Venter before, as his former company Celera Genomics was one of the two groups responsible for publishing the first human genome sequence. However, Craig Venter is crazy. So crazy, that Craig Venter just might kill you if you get him angry. Why, you ask? Here are five starter reasons:

5. He’s infamously cut-throat

He’s been called alternately “Darth Venter“, “a one man superpower “, and “an asshole”. But how did Venter get this reputation? It likely has something to do with him patenting human gene sequences for profit. Also, blowing up Alderaan.

4. He was in Viet-Nam

That’s right, Venter was in the shit. Probably explains the 1000-yard stare in this picture.

3. He’s a billionaire

Craig Venter is so damn rich that he could pay to have a piano dropped on you and your loved ones, every day of the year for the next 300 hundred years [($1,000,000,000 / $8000)/365]. Plus, he has two magic science boats, a team of brilliant lackies, and a cool rain jacket.

2. He sequenced his own genome

He really did. If you think one Craig Venter might kill you, imagine what an army of clone-Venters could achieve.

1. His lab recently created the first synthetic genome

If you thought Venter’s heyday had past, think again. The J. Craig Venter Institute is has been busy creating life from scratch in the lab. While the JCVI argues that their technology could be used to create bacteria that produce electricity/oil/hydrogen, I can only think this might be the start of something bad, especially coming from Darth Venter.

1. Ape and Human – Sahelanthropus tchadensis

When people talk about proto-humans, species in the genus Australopithecus (e.g. “Lucy”) are the usual suspects. I personally prefer our friend Sahelanthropus tchadensis, pictured above. While S. tchadensis is much more on the ape side of evolution than it is on the human side, it has been suggested that it was fully bipedal (walks on two legs), making it a nice transition form from tree-swinging apes to hop-scotching humans.

2. Reptile and Mammal – Therapsids

I remember watching a movie in elementary school and being perplexed by the statement that mammals evolved from reptiles. It wasn’t until my comparative vertebrate anatomy class in my sophomore year that the mystery was cleared up! Therapsids, like Lycaenops (“Wolf-face”, ha!) pictured above, are quite basically mammal-like reptiles. The main features of these wolfy-lizards are: large developed jaws, a sleeker and lighter skull, and placement of the legs below the body to facilitate fast “galloping” as seen in the modern pooch. Some scientists even believe that therapsids had by this time evolved mammal-like hair (fur).

3. Fish and Amphibian – Tiktaalik

You remember the Tiktaalik, don’t you? He remembers you! Just kidding, but this squirmy little guy wins the award for Most Likely to Frustrate Believers In Intelligent Design due to his existence being predicted long before his bones were even found in 2004. Also, the Tiktaalik is Canadian (found on Ellesmere Island, Nunavut)! For that, I give him a four fleshy-lobed fin salute.

4. Invertebrate and Vertebrate – Larval Urochordate

Another difficult evolutionary step to visualize is the transition between worm-like sea beasties and fish with basic spines composed of vertebrae (i.e. vertebrates) . The leading hypothesis is actually quite ingenious and satisfying, much like this blog. It goes something like this: In the fossil record, oceanic vertebrates appear suddenly 550 million years ago. Up until to this point, the sea was dominated by crazy giant insects and Urochordates, who were (and are!) invertebrate sessile filter feeders (like a sea sponge). The key fact is that the earliest life stage (larval stage, pictured above) of the Urochordate was similar to a tadpole, and even had a rudimentary spine. The hypothesis states that some natural selection situation caused the Urochordate to stay a larva for longer and longer until eventuall, the sessile adult stage was totally eliminated (this process is called neoteny in evo-devo jargon). So in the end we were left with a nice little tadpole who eventually gave rise to all the fishies in the deep blue sea. As for mollusks and the like…I have no idea!

5. Unicellular and Multicellular Life – Cellular Slime Mold

When life first arose, it was almost definitely in the form of one-celled creatures. While many of these simple organisms have persisted in one form or another to present day, others somehow made the jump from being composed of a single cell to being composed of many. This is not a trivial evolutionary step! Now, while the theoretical background of the evolution of multicellularity is a little mind numbing and by nature non-empirical, there are existing organisms that can give us clues about how it might have occurred. For example: the weird ooze pictured about is a cellular slime mold that begins its life as a group of unicellular organisms, but eventually matures into an enormous multicellular (and gooey) individual! Weird!

6. Primordial Ooze to Unicellular Life – ???

What am I, a biochemist?