The MinION Nanopore sequencerMany of us has heard of DNA sequencing and many news and journalism sites often brag about the use of DNA sequencing as an extremely robust and advanced technique. That is true but it is also very accessible compared to a decade ago. “The Cost of Sequencing a Human Genome,” National Human Genome Research Institute (NHGRI). [Online]. Available: https://www.genome.gov/27565109/the-cost-of-sequencing-a-human-genome/. [Accessed: 23-Jun-2018]. Sequencing technology has advanced so far that prices has dropped from almost $10,000 per megabase to less than a dollar per megabase. The graph above shows the rapid rate of increasing affordability of DNA sequencing, dropping by half almost every year. I have been lucky enough to have hands-on experience with the MinION and I'm here to share my experience with it. The general pipeline of using the sequencer is as follows: Extraction of Genomic DNA (gDNA) -> Library prep -> Loading of DNA samples into the MinION flow cell -> Sequence analysis. gDNA is routinely prepped via kits such as the Qiagen gDNA extraction kit but needs to be prepped by a library kit by Oxford Nanopore Technologies. The prepared sample is then loaded into the sequencer's flow cell and the sequencing is ran on the MinKNOW program. Simple as that! DNA bases are moved through a nuclear pore that is usually used in nature to move DNA in and out of he nucleus of a cell and what is unique about this is that this pore has been modified to be able to change the current that corresponds to the DNA bases: A, T, G and C. This allows us to do sequencing according to the current recorded. What so revolutionary is the size of a DNA sequencer. Unlike the huge conventional sequencers like Illumina, the sequencer, about 9 inches, is small enough to be bought out to field for DNA sequencing, assuming the necessary equipment is available. This means that, with the proper training and equipment, clinics and hospitals may be able to bring this technology to the general public for precision and personalized medication.
The real work comes from the downstream processing of the data you get from the sequencer which may require a bioinformatician to analyze the data. In 50 years when such analysis is a common skill and this technology is cheap enough for clinicians, this can be a real game-changer to diagnosis for illnesses such as cancer, diabetes and many others.
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(Photo credits: The New Yorker) Everyone knows bacteria are small microscopic organisms millions of times smaller than us. They can be helpful or harmful to us and they are everywhere. So have you ever wondered how such a tiny little thing can cause us to get sick or even cause death to some? Many think of bacteria as these simple small organisms that are incapable of communication and all do their own thing. This however is very wrong. Think about it like in society, no one person can achieve a giant feat by themselves. And in the case of the bacteria, no one bacteria can conquer a human millions of times larger than them by themselves. So now the most logical deduction is that bacteria work together to conquer this feat. We all know that bacteria can multiply really quickly, hence easily achieving large numbers. But if bacteria can't tell each other what to do, how do they achieve this? Well bacteria achieve this via a system known as quorum sensing (QS). QS is a system that only activates at high cell density; when there are a lot of bacteria. This is how bacteria can tell how many of themselves are there, or at least when there are many copies of itself around. This is why we call it the social media platform of bacteria. So when there are enough copies of themselves, the bacteria are now able to conduct a single activity using a collective effort such as causing disease in a human. I'm sure we are all relatively familiar with hormones, the chemical signals that sends messages to various parts of the body we all learnt in high school biology. Well bacteria don't exactly use hormones, but it is a similar system. Now this system is different in the two classifications of bacteria, Gram-negative(GM-) bacteria and Gram-positive(GM+) bacteria. We are going to talk about GM- bacteria first as it is a simpler system. Just like in a endocrine system(hormones system), chemical signals are produced to talk to one another. Here we see a diagram of how QS works essentially in GM- bacteria. Now don't be afraid of the complexity, it is actually a rather simple system. First let us identify the legend of the system. The red quarters are the chemical signals, the autoinducers. The yellow fractions of circles are the receptors. The autoinducers are able to be read by the receptors and the receptors is what tells the cell what the chemical signal means.
So now looking at the figure for low cell density, we can see that there are very little autoinducers visible. This is because the cell is alone, hence the amount of autoinducers produced in the environment is very little. This is similar to Facebook. When having a small social circle, the number of "likes" you get on your posts is small. The opposite is true when having a large online social circle. This is the basis of QS and is what is happening here in this diagram. Now looking at this analogy, look at the figure for high cell density. This cell is now not alone,many other cells are present. This allows for many more autoinducers to be produced in the surroundings, allow the recptors to pick this up, allowing the cell to realise it has many "likes on its posts". This allows the receptors to do its second function. This allows the receptors to activate genes to produce certain proteins. Now the bacteria is able to produce these genes activated by the receptor. This, when conducted by harmful disease-causing bacteria, is the cause for bacteria making harmful toxins in our body. And this is how this large social network of microorganisms can cause disease or a large orchestrated activity.
(Photo credit: Nubites)
GM food, otherwise known as genetically modified food, some say it's safe, some say it's hazardous. Mysterious to many and a staple to others. Supposedly highly sought after by farmers. So what really is GM food? Does GM food harm or help people?
Well let us speak about what GM food is and how it's made. GM foods are food products genetically modified to have certain traits. An example of such a food is seedless grapes, for the convenience of people who do not wish to deal with the numerous seeds from the grapes. So as we can tell, these traits differ from what is the norm of these food products when found in nature. Most people think that only food products from plant sources can be genetically modified, however this is very incorrect. Meats are most likely genetically modified. Such as in salmon that are modified to be larger and stronger than usual in the wild to increase yield of salmon products in aquaculture. It sounds extremely profitable to farmers to have a improved version of everything right? Well GM food does have its drawbacks to farmers as well. Notice how GM food, especially plant products, are significantly more pricey than normal products? Well this is because companies selling seeds of GM food tend to disallow reproduction of the plant. This is for the need of farmers to constantly buy seeds so that the company earns more profit. So what good has GM food brought to humans? Well there is a famous example that testifies the power of GM food and that is the Golden Rice Project ran by the Golden Rice Humanitarian Board. Golden rice is a genetically modified version of rice that, as the name suggests, is gold in colour and is packed full of Vitamin-A. The Golden Rice Project was originally started to combat night-blindness, a Vitamin-A deficiency, commonly occurring amongst less developed countries where access to fresh and nutritious food is scarce. With golden rice, this staple food satisfies the necessary Vitamin-A daily intake and has been a phenomenal innovation by the biotech industry and prevents about a third of all under-five deaths, which amounts to up to 2.7 million children that could be saved from dying unnecessarily. Now time to answer the question that everyone wants to know, is GM food harmful or not? Well the answer is yes and no. Towards us humans, GM food is generally safe and is approved by the FDA ( Food and Drug Administration). In some rare cases, some people may develop certain allergies. Towards the environment however, GM Food is extremely harmful. Genetically modified plants such as pest resistant vegetables can cause the decline of certain pests in an area. This doesn't sound so bad, heck it even sounds great. However, this is extremely bad to the environment. Some predators may rely heavily on this pest and killing it off may destroy the balance in the ecosystem. A simple example of this can be represented in a simple food chain as represented below. Maize/Corn -> Corn Borer (Maize-eating worm) -> Birds Now to put it simply, the bird populations will dwindle down. Why? Well the birds rely on the corn borers for food but when GM Corn is introduced, the corn will contain Bt proteins, a toxin to the corn borer, hence killing the corn borer, reducing the amount of food sources for the birds. Another problem is the possibility of the corn borers gaining a resistance against Bt, hence giving rise to a generation of unstoppable corn borers. Now let us look at the same food chain that is slightly different. Maize/Corn (Nectar) -> Monarch Butterfly Now this is where it gets interesting. Some of ya'll may think so what? This isn't affecting humans. Well it does here. With the nectar of the maize now being toxic to the butterfly, the maize will not be able to be pollinate. You see, as the butterfly goes on the flower of the maize to drink nectar, the pollen falls on the butterfly. As the butterfly travels to other maize flowers, the pollen from the butterfly falls onto the new flower. This is known as cross-pollination. Without pollination, the flowers will never be able to turn into corns which are the crops we humans want. Maize being a staple to most countries of the US, GM crops may destroy the US food export economy and food supply of maize. This is just one of the many examples of GM crops and its impact on the environment, many more examples are out there. From this all, we can conclude that GM food has no harm onto humans, in fact it has brought us alot of good. GM food however, harms the environment and can cause a lack of biodiversity. Now it's up to you to decide if you support GM food or not. (Photo credits: Wonderfest.org) I'm sure most of you have seen a Jurassic Park movie, or at least know the plot of it; collecting dinosaur DNA from fossils and editing the code into the DNA of existing animals to lay dinosaur eggs and use this to form a giant prehistoric amusement park! Sounds amazing doesn't it? Well unfortunately it's not as simple as that.
Well to simply put it, unfortunately it is impossible to revive dinosaurs because first, DNA has a half-life of 521 years and that's way before biology was even a thing people knew about. Second of all, even if we had dino DNA, it is impossible to put a whole genome into another animal's genome and have a dinosaur offspring be born. Yet, Jurassic Park was a movie that did inspire genetic modification which is now widely used in research now. So how exactly does it work? Now note that there are many ethical debates about how ethical it is to edit an organism and play god but today we are only going to discuss how it is done. Well first we need the locus(specific location of a gene) that we want, and we need to ''cut'' this gene out. To do this we need restriction enzymes that are specific to this locus. With the work of restriction enzymes, we have the isolated gene(s) we want. Next we need a medium to put the genes in. Most of the time genes are put into bacteria to makes certain proteins we want such as insulin for diabetics. But since we are looking at how to edit an organism, we need to edit or replace the genes in a genome of the organism. So first we require special nucleases, enzymes that break up nucleotides. This will allow us to cut up any area we want in the DNA. Now we need to put the genes we want in the cut we made. Using DNA ligase, an enzymes that acts like glue, we can stick the genes we want into the organism's genome. Now note the genes we have taken are single stranded while the DNA is double stranded. So to complete the sequence, we need to use reverse transcriptase, an enzyme that works like a copy machine, this allows us to finish up the DNA sequence to make complementary DNA. Now the sequence editing is complete. It is a long confusing process but if you want to know how to do genetic engineering, this is the basics of it! (Photo credits: Wikiwand) The biotech industry has always been a flourishing industry with constant new innovations. This led to a rise in investments in the global biotech economy. Costs of doing biotech research has also significantly decreased. One example of cheaper research costs is the cost of DNA sequencing. Sequencing technology has advanced so far that prices has dropped from almost $10,000 per megabase to less than a dollar per megabase. The graph below shows the rapid rate of increasing affordability of DNA sequencing, dropping by half almost every year. Time and time again the biotech industry amazes us with its remarkable growth and life changing works such as gene therapy and genetic modification.
So why is the biotech industry dying? To answer this question first we must look at what the biotech industry is doing for the general public. Lets name what the biotech industry has done to change lives: Gene therapy, creation of GM Food, Cancer treatments... ... ...well? Not many more huh? This is the problem of lack of transparency and educating the public on what the biotech industry actually is doing! Perhaps you could name research going on such as stem cell research or research for new vaccines and antibiotics, but the general public doesn't seem to know more! If we do not educate our investors in what we are actually doing, how are we going to maintain the confidence of our investors? Many of you people in business are there shouting " WITH GOOD MARKETING OF COURSE!" Well this is where the second issue comes about. Products of the biotech industry is falsely being marketed. To understand how it's falsely being marketed, me must look at the general public's view on how our products work. Lets look at sequencing technology again shall we? To a general public's point of view, DNA sequencing is most likely to perhaps get a blood sample, run it in a machine and voilà! We now have your whole genome. This is very wrong! It is definitely not as simple as that! Marketing and advertising our products so falsely like this is extremely detrimental to the biotech economy. Sure, we will get investors in the short run but once we are unable to produce products of the level of advancement we are advertising as, we will lose these investors! Soon, we won't have any investors and the whole industry will crash. Losing investors is one thing but once we start to lose the confidence of people looking to join the industry, all we are left with is our senior professors with no one to mentor or teach. That might just mark the end of an era for the advancement in biotechnology. And this is why the biotech industry might fall. If we don't start changing the way the biotech industry is run, this economy will just crash and burn. |
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