Category Archives: Biological Sciences

Evolution Can Be More Random Than You Think

Charles Darwin’s Origin of Species postulated that evolution takes a directed approach toward increasing fitness. A recent discovery suggests that evolution doesn’t always need to have a direction. Dr. Matthew Pennell’s findings suggest that evolution on a chromosomal level can have a high degree of randomness.

Dr. Matthew Pennell, an evolutionary biologist specializing in Computational Biology at the University of British Columbia, recently wrote a paper that gives more insight on evolution, entitled Y-Fuse? Sex Chromosome Fusions in Fishes and ReptilesIn this paper, Dr. Pennell uses software and algorithms to determine the factors that drive sex chromosome fusions. Unlike traditional biologists, Dr. Pennell does all of his work on his MacBook instead of using pipettes and microscopes.

Source: Wikimedia Commons, Dr.Pennell uses computational approaches, such as Mathematica for his research.

Source: Wikimedia Commons, Dr.Pennell uses computational approaches, such as Mathematica for his research.

This video, courtesy of universityofbc via Youtub, introduces UBC Killam and NSERC postdoctoral fellow, Dr. Matthew Pennell and talks about his research

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“The simple fact that Y autosome fusions are way more common than W or X or Z, suggests it’s probably just random, which is a kind of interesting and cool result that this huge thing in our genome and across all genomes is just random chance, and this random chance explanation is the most consistent with our data.”

 -Dr. Matthew Pennell

During his graduate studies, Dr.Pennel was part of a team that integrated chromosomal information of thousands of species into an electronic database called The Tree of Sex, which we describe in further detail in our podcast below.

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Now that we know randomness is involved in sex chromosome evolution another question arises: Is sex determination an absolute process? 

As we will soon see there are species, such as the Stickleback fish that change their sex determination system from XY, to ZW, to temperature controlled and so on. However, does this mean that we humans might experience such a change in the future?  

Source: Flickr Commons, Huamns have 22 pairs of autosomes and 1 pair of sex chromosome

Source: Flickr Commons, humans have 22 pairs of autosomes and 1 pair of sex chromosome

“They keep reinventing how they make males and females and this is really interesting and crazy because making males and females is the most basic thing animals do….But they keep switching around how they make males and   females, which I think is pretty cool.”

-Dr. Matthew Pennell

In addition, we were fortunate enough to have the opportunity to interview Dr. Pennell:

https://youtu.be/9obgQ7mI5Ac

Before the interview with Dr. Pennell, our group had a lot of difficulty understanding the premise and messages of the paper. Dr. Pennell provided us with simple insights on the different facets of the evolution of sex chromosomes – from the creative variety of ways that nature determines sex in species, to the mechanisms which drive sex chromosome fusions. Although a lot of these concepts were hard to understand at first, the premise of the paper is very simple to understand – computational biologists often work with real world data sets (ie. “The Tree of Sex”, and try to fit their models to them to determine the relationships between the scientists’ predictions and what’s really happening. In this specific paper, Dr. Pennell and his team concluded that the different models did not relate to the given dataset and the explanation for the real data is attributed to randomness.

 

We would like to give a special thanks to Dr. Matthew Pennell for his time and explanation of his paper.
Authors: Justin Yoon, Julia He, Radu Nesiu, and Matt Golf (Group 2)

Looking deep within a cell, super resolution microscopy technique improved by researcher at UBC

What do you think is the smallest scale visible through a light microscope? Bacteria in micrometers? Guess again. The answer is thousands of times smaller. Last year, a Nobel Prize in Chemistry was awarded for the development of super-resolved fluorescence microscopy, which brought the imaging scale down to nanometers (billions of times smaller than a meter). Recently, Reza Tafteh, a PhD candidate from the University of British Columbia further improved on this technique. The specific version of super resolved microscopy Reza improved on is called single-molecule localization microscopy (SMLM), and it allows scientists to image deeper into a target cell with greater accuracy. An interview with Reza is available in this podcast: 

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The computer system used to operate Reza’s microscope, photo credits: Ivan Lan, Reza Tafteh

As Reza explained in the podcast, SMLM achieves high resolution through image reconstruction. Imagine looking into a traditional microscope like looking down on the city of Vancouver at night from an airplane above. It is hard to tell the contour of the city with the limited lighting. Using fluorescence on the target sample is like turning on the building lights in the city, allowing us to observe things that aren’t normally visible under the moonlight. Now imagine that these lights are constantly on and extremely bright. If the location of the lights are too close together, many of them may seem blended with each other. This makes it harder to tell apart (or resolve) smaller structures such as narrow streets from one another; which in this case is like trying to resolve narrow structures within cells. SMLM reduces this effect by turning the lights on and off at different times for different parts of the city, which you can find more details in the podcast and the video.

However, the traditional SMLM technique isn’t perfect. Alongside major limitations in stability mentioned in the podcast, another major limitation is the distortion of an image caused by changing refractive indices through several different media, just like a pen appearing bent when inserted into a cup of water. Refractive indices varies from the cover-slip to the media (the substance the cell is placed in for imaging), and from the media to the cell.

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Refractive Index difference causing image refraction. Source:Flicker Commons, Author: Mohammad Tajer

Reza Tafteh has improved on both of these limitations. His approach can produce stabilized images with reduced distortion when imaging deep into samples. Here is a video of him demonstrating his stabilization technique.
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Reza is now trying to push the limits of SMLM even further, he sets his eyes on improving the technique’s inability to image live cells, while continuing to increase the resolution and clarity of microscopy images. It is exciting to think that specific cellular structures such as heart cell calcium receptors can be observed in unprecedented detail. It is not hard to imagine the many biological fields that can benefit from this microscopy technique. Reza’s improvement on SMLM  can potentially lead to better understanding of molecular biology, which may one day lead to new treatments for diseases such as central core disease.

Music and sound material used in podcast:

A sincere thank you to Reza Tafteh for participating in this project.

By: Group 3, Brian Cheng, Esther Lo, Ivan Lan, Sainan (Stephanie) Liu

The CRISPRs Fever

You may remember from biology textbook that we can edit genetic material using restriction enzymes, a DNA-cutting protein structure. Using this we can learn about gene functionalities, search for disease treatments or increase yields of crops. Controversially, it also made unnatural creations possible. However, different gene targets require different enzyme structures, just like to open different doors you need different keys, and making these “keys” turns out to be complicated, expensive and time-consuming, which might have kept most of the “fantasies”, such as “super human” or other wired things, away from reality for now for better or worse.

by PuraVida_Fotografie from Google Image "genetic mutation" Labeled for reuse

by PuraVida_Fotografie from Google Image search “genetic mutation”, labeled for reuse.

However, what if all the “doors” also have the same type of “digital locks”, and all you need to change is the password? CRISPRs (clustered regularly interspaced short palindromic repeats) turns out to be this “lock”. It contains repeated sequences sandwiched with spacers (unique genetic information) in between. The spacers are external virus genes kept in bacterias and served as the “criminal records” so that when invasion happens again, the bacteria can send an “army” of gene-cutting enzymes, called Cas9, to cut the recognized viruses’ DNA apart.

"Crystal Structure of Cas9 in Complex with Guide RNA and Target DNA" by Hiroshi Nishimasu, F. Ann Ran, Patrick D. Hsu, Silvana Konermann, Soraya I. Shehata, Naoshi Dohmae, Ryuichiro Ishitani, Feng Zhang, and Osamu Nureki - Crystal Structure of Cas9 in Complex with Guide RNA and Target DNA http://dx.doi.org/10.1016/j.cell.2014.02.001. Licensed under CC BY-SA 3.0 via Commons

“Crystal Structure of Cas9 in Complex with Guide RNA and Target DNA” by Hiroshi Nishimasu, F. Ann Ran, Patrick D. Hsu, Silvana Konermann, Soraya I. Shehata, Naoshi Dohmae, Ryuichiro Ishitani, Feng Zhang, and Osamu Nureki – Crystal Structure of Cas9 in Complex with Guide RNA and Target DNA http://dx.doi.org/10.1016/j.cell.2014.02.001. Licensed under CC BY-SA 3.0 via Commons

In 2012, scientists have proven that instead of making restriction enzymes for different genes, we can simply replace these “criminal records” and use the same Cas9 “armies” to cut desired genes with much less time and cost. You can find the details in this following video.

YouTube Preview Image[by McGovern Institute for Brain Research at MIT]

Nature , Science and many major media have unanimously deemed CRISPRs to be a revolution. Radiolab has discussed its ethical controversies as if the realization of the technology is right around the corner. It has been portrayed as such a simple and approachable method that people even claim to provide CRISPR DIY kit for experiments at home.

However, I think despite these attentions,  the reality is that we are still far from ready to harness CRISPRs. Although many researches has already been using it to edit genes in a variety of bacterias, plants, and animals within a short 3-year period, few studies focused on the limitations and functions of CRISPR itself. Some research was done too early without waiting for the technology to mature, such as the research using human embryos, which has resulted in a less satisfactory result. Some researchers commented that CRISPR can be less accurate than expected and may not be the most efficient and cost-effective solution for certain problems on Quora. Scientist Konstantin Severinov on Quanta Magazine also pointed out that it is still unknown whether defending invaders is the major usage of CRISPRs since many of these spacers appear to be genes of viruses that are long gone. It might be a good time now to slow down and maybe build the technique from ground up concretely first.

by Sainan Liu

Lethal Adaptations In Nature: Tapeworms linking infection and cancer

Parasites are some of the oldest and basic forms of life on the planet. Each and every species having honed their specific traits to leech and infest their host often through millions of years of natural selection. It’s a scary thought, to say the least. And one particular widespread parasitic species has recently been discovered to have made significant jump. Tapeworms.

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Tapeworm proglottids (50cm in length)
Author: Nathan Reading via Flickr Commons

It’s a certain parasite that I’m quite concerned about every time I pick up an egg sandwich at local gas station. Tapeworms often infest the digestive tract of animals and use their hosts are intermediary stages in their life cycle. In the case of humans, that infection is usually caused by consuming undercooked foods. The photo of a vomited tapeworm above was taken from a pregnant 26-year-old patient who had been living in East Africa. As you can see, they can grow immensely large in your intestine without any symptoms (one of the optimal traits of a model parasite).

If that wasn’t enough to make your skin crawl, a study published in 1999 found that up to 75 million people may carry the dwarf tapeworm with 25% of children affected in certain areas. When taking a much closer look with an electron microscope (image below), you can clearly see that tapeworms have an effective adaption on its head: suckers, muscular grooves, and hooks to latch onto your inner digestive system. Though rarely lethal, newly published research has uncovered a potentially deadly link between these worms and cancer.

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Hymenolepis microstoma (rodent tapeworm)
Author: Magdalena ZZ via Wikimedia Commons

A brief report was published this past week in the New England Journal of Medicine, detailing an unprecedented case of a tapeworm (or any parasite of that matter) transferring cancer cells into a human. The team of American researchers led by Dr. Atis Muehlenbachs from the Centers for Disease Control and Prevention claim it to be the first reported case of its kind. Easing public fears, it’s also been described as extremely unusual and rare.

NEJM_Issue-12

Source: The New England Journal of Medicine

The story begins in Columbia in 2013 when a 41-year-old man stumped local doctors of his deteriorating condition. He was ill, losing weight, and struggling with a prior HIV infection. Upon further examination, a CT scan of his lungs showed many tumorous growths which were made of cells not identified as human. That shocking revelation prompted them to contact scientists at the U.S. CDC.

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Figure 1 (A). Radiographic and Pathological Features of Malignant Hymenolepis nana.
(Muehlenbachs et al. 2015)
Source: The New England Journal of Medicine

The CDC center in Atlanta found the cells to be much smaller than human ones. Ten times smaller. Eventually, a genetic analysis found the strange cells had DNA from Hymenolepis nana (the dwarf tapeworm). The current theory is that the HIV patient’s compromised immune system and a mutation in the tapeworm caused this spread of cancerous cells from parasite to host.  For a more detailed explanation of the biological mechanisms involved, check out the helpful video below courtesy of the New England Journal of Medicine.

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It’s important to note that original patient died before he was correctly diagnosed. However, perhaps the results of this investigation may prove to be fruitful for others in the future as millions of people suffer from both tapeworms and HIV.

Tragedy aside, one has to admire how amazing this discovery is. For myself, I’m so impressed by the international collaboration of medical experts as well as the nature of the case. Even the language used in the original paper sounds very dramatic, Invasion of human tissue by abnormal, proliferating, genetically altered tapeworm cells is a novel disease mechanism that links infection and cancer.”  (*I’ve underlined some phrases to emphasize their impact.)

It feels like something out of the TV show House MD: a medical mystery, bizarre clues, the elusive search, and the extraordinary resolution. It’s the kind of passion that I believe Muehlenbachs shares.

“We were amazed when we found this new type of disease – tapeworms growing inside a person, essentially getting cancer, that spread to the person, causing tumor…” – Dr. Atis Muehlenbachs of the U.S. CDC

Furthermore, I’m sure this case will spark a new field in medical research of cross-species oncology. I admit that this mutation may not be very beneficial to the tapeworm as it prematurely kills off its human host and may end up being a once-in-a-life phenomenon. Nonetheless, it’s a great example of how a parasite can dramatically change the relationship with its host and how we should approach treatment of unknown diseases.

By Paul Yi

Commented on:

Esther Lo’s Green Rush in Canada

Matthew Golf’s Free Speech for Science in Canada

Luxi Xu’s Work-Life Balance

 

Brains and games in 21st century – How do video games affect us?

There is a lot of debate regarding how video games influence our brains development and whether or not games are beneficial or damaging. Scientists have examined both sides and the question that needs to be answered is whether games are beneficial or they are transforming us into machines.

digital mindcredits: http://guardianlv.com/2013/08/researchers-develop-mind-control-using-the-internet-video/

Some studies show that prolonged exposure to video games has negative effect both on the body and the brain. Games decreases attention span, increase the risk of obesity and violent games decrease sensitivity towards aggression. The implications are troubling since decreased attention implies lower academic performance and obesity is a health risk factor. Furthermore it is shown that decreased sensitivity towards aggression not only makes us consider aggressive behavior acceptable but it also increases the chance that we will become aggressive.

aggressive gamers

credit to: http://yoursinglesourcefornews.com/ academics-debunk-theory-linking-violent-video-games-with-aggression/1379/

Another fact that must be considered is repetitive tasks in games. Because there are lots of games that become repetitive and have reward systems that encourage that behavior gamers are exposed to lose of creativity. Since repetitive tasks are better suited for a computer we could ask ourselves if our mind is encourage to become a basic processing unit.

However, there is another side of games which was investigated by researchers and the findings encourage people to become casual gamers. The benefits from games are as follow: better cooperation skills, adaptation to new challenges, fast reaction time and better attention to details.

brain-skills-games

credits: http://www.jklmgames.co.uk/how-games-can-train-the-brain

Besides the standard types of games we should also consider games that involve movement (e.g. some Nintendo Wii games) which are shown to motivate exercise. Those type of games should become encouraged in populations with increased risk of obesity, where the reward system should be tailor for the customers.

The tricky part of the games is the reward system which acts as a drug since it releases dopamine which is the hormone for excitement. Using this we can develop games that can stimulate people to learn and train. A study done on surgeons  showed it is possible to increase job performance via gaming. Here is a TED talk about games and how we can use them to construct a better world.

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Based on what we seen so far casual consumption of non-violent games have beneficial effects, however one must take extra care since crossing the line and becoming an addict can severely impact us.

Radu Nesiu

Newly discovered hormone can possibly change the future of weight loss?

Obesity is a leading health problem in Canada and many other countries throughout the world, with it becoming one of the leading causes of death worldwide. However, what if someone who is clinically obese can decrease their body fat simply by taking a pill? Modern prescription drugs for weight loss do exist; however, they aren’t very effective and can have messy side effects! 

Obesity, Author: Tony Alter, Source: Flickr Commons

Well, recent scientific discoveries may have found the perfect candidate to serve as a replacement for the current prescription drugs available for treating clinical obesity. Irisin, a hormone produced by skeletal muscle cells during exercise is capable of burning fat tissue reserves when introduced into circulation. Irisin achieves this by converting white fat cells, which are the fat cells used to store fat in the human body, into brown fat cells, which are fat cells responsible for burning fat to produce heat. 

An article published in Nature showed that increased irisin levels in humans and mice causes more brown fat cell development, which lead to an increase in energy usage in the form of burning existing fat tissues. This increase in energy consumption occurred in a controlled environment, without any changes in the mice’s amount of physical movement or food intake, which can lead to induced weight loss in obese individuals (Bostrom et al.). 

Tension quickly rose due to researchers speculating if irisin actually exists in the human body, with studies criticizing the methodologies that Bostrom et al. used to detect irisin within humans. However, a recent article published in Cell Metabolism  by Bruce Spiegelman showed definitive proof that irisin does exist in the human body. Instead of using more traditional methodologies commonly used to detect hormones in the human body; Bruce Spiegelman and his colleagues used  a new method involving mass spectrometry to accurately detect and quantify the amount of irisin in participating human subjects (Spiegelman et al.).

Isn’t that great then? Shouldn’t pharmaceutical companies quickly adapt the hormone irisin and start producing a weight loss pill? However, I think the issue of time restricts any advancements in the pharmaceutical industry in actually producing such a pill. Since irisin has only been discovered in mice recently, and confirmation of irisin in humans was only published in August 2015. 

Diet Pills

Diet Pills, Author: joaneQEscobe, Source: Flicker Commons

As well, I would like to bring up a similar weight loss drug that was invented in 1933 that also showed the same promise as irisin. DNP, or 1,3 dinitrophenol was shown to increase metabolism rates by converting chemical energy into heat. Though the mechanisms that they occur aren’t identical, the end result of increased body metabolism and body temperature is observed for both DNP and irisin. DNP quickly became a wonder drug that took North America by storm; even now, DNP can be purchased online as a diet pill. However, tragic deaths have been associated with usage of DNP as a weight loss treatment, with terrible consequences of DNP overdosing including fatal hyperthermia (extreme body heat).

I feel that with something as promising as irisin being capable of helping obese individuals loose weight, the pharmaceuticals, FDA, and researchers have to take responsibility and caution in the future. Making sure that if irisin does become a prescription drug to treat morbid obesity, the tragedies associated with DNP will not occur again in the 21st century. 

Here’s a video on Scishow explaining current weight loss pills :

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By: Yu Chieh (Brian) Cheng

Jelly-like Features of Disease-causing Proteins

I remember when I was a kid (or even now), one of my all time favourite snack is strawberry flavoured Jell-O (or jelly). Not to mention, making it was so easy and so much fun, as the strawberry aroma would fill the kitchen.

C. elegans worm used in the study. Source: Wiki Commons

C. elegans worm used in the study. Source: Wiki Commons

Scientists at the University of Cambridge, led by Peter St George-Hyslop used nematode worm C. elegans as a model for amyloid lateral sclerosis (ALS) and frontotemporal dementia to study the physical properties of FUS, an essential RNA-binding protein in the body. The behaviour and physical properties of FUS can be closely compared to that of jelly. All RNA-binding proteins have two common domains: one for binding RNA and the other where the protein appears to be unfolded. It is at this unfolded region that the FUS undergo a process of reversible ‘phase transition’, which closely resembles the formation of jelly.

Comparison of ALS-affected and normal nerve cell. Source: Sarah Scoles

Comparison of ALS-affected and normal nerve cell. Source: Sarah Scoles

One common characteristic of all neurodegenerative disease is the irreversible accumulation of misfolded or mutated proteins aggregates in the brain, which as a result causes damage to the brain and disrupts communication between brain cells.  FUS is one of many types of RNA-binding proteins that is essential to the brain. It is essential in the regulation of protein synthesis, with functions in the nucleus and cytoplasm of a cell. However, the accumulation of mutated FUS and other associated proteins is also the underlying cause of the neurodegenerative diseases such as ALS and frontotemporal  dementia. Until recently, the significance and how FUS proteins affects the development of these neurodegenerative disease has been unclear.

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[Video courtesy of C.D. Net]

FUS starts out as soluble monomers (like the initial powered-form of jelly), and forms distinct localized accumulations. As it further condenses, a thick gel-like hydrogel structure is formed (like the formation of jelly after it cools in the fridge). This process can be reversible (like warming and cooling jelly repeatedly). Furthermore, during these transitions, RNA and proteins are continuously released from protein assemblies (like suspended fruits in the jelly as it is re-warmed and re-cooled).

The above processes are beneficial because it allows the cells to accumulate cellular machinery in a confined three-dimensional space (with no cell membrane required)  when needed to perform key tasks, but also disassemble when not needed. In addition, it is also faster and less-energy costly compared to the formation of a membrane-bound vesicle.

Although FUS is able to carry out vital cell processes by interchanging between different states, “this essential property also makes them vulnerable to forming more fixed structures if mutated, disrupting their normal function and causing disease” says Professor St George Hyslop. Mutation of FUS causes it to over-condense and become a thick fibrous gel, irreversibly trapping the essential RNA and proteins required for protein synthesis. It is the accumulation of misshaped FUS and other RNA-binding proteins that causes serious neurodegenerative diseases. However, further research and understanding of what are in these assemblies can bring us one step closer to curing ALS and other neurodegenerative diseases.

 

 

On Wasps and Matricide

First, think of a wasp colony as a monarchy, where workers diligently provide for their queen.  Assume the queen is unsatisfactory, what would happen? A violent revolution perhaps?  This article on a study done by Kevin J. Loope explains how wasps are fully capable of committing matricide under the right conditions.

Matricide is not particularly uncommon in the insect world.  Many species such as crab spiders take part in matriphagy, or mother eating.  Wasps, on the other hand, depend on the queen to forage for food to feed their larvae.  Normally, fully grown workers are the ones that turn on their mother.

Source: Marjan Smeijsters on Flickr Commons

New wasp nests are formed in the spring after fertilized queens have finished hibernating.  Solitary queens construct the nest, lay eggs, and care for her larvae.  Only after the larvae have matured into workers, all of which are female, do the queen focus on reproduction and leave the other duties to her offspring.

An average wasp queen lays around 100 eggs each day.  Some workers are capable of laying eggs, but only for drones, or male wasps, and are discouraged by the queen through attacks or egg eating.   While in most cases wasps let their mother be responsible for passing on their genetic data, workers may get rid of the queen if being able to produce their own offspring outweighs the loss of new siblings.

wasp2

The queen’s mating practices are an important factor.  Queens normally only mate once or twice, but that does not imply an even distribution of full siblings.  In single-father colonies or colonies skewed to have many full siblings, workers are more closely related to their nephews than their brothers.  Loope noticed that because workers are willing to take care of closely related nephews, females will kill the queen to have the colony raise their young instead.  Wasps are believed to be capable of identifying its relatives.

Past research also reference low queen productivity or queens producing only males as reasons for matricide.  From this we can hypothesize that while wasps may work for the greater good on the colony, the queen is not necessarily vital to the continued welfare of the collective.  It puts a new light on what some would believe to be mindless workers.

Here is a basic video on the various stages of a yellow jacket wasp’s life:

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credit to ScienceOnline on Youtube

blog by Ivan Lan