Team:Lund/Blog

iGEM Lund 2019

Blog

Welcome to the iGEM Lund blog. Here we've posted articles about synthetic biology, science and our project, in means of spreading our shared interest. If you're a listener instead of a reader, head over to Public Engagement to listen to our podcasts with other teams. Happy reading!

2019-07-16

Toxic metals

Toxic metals (commonly referred to as heavy metals) are widely spread throughout the world today. You’ve heard of the dangers of arsenic, lead and mercury before however, it may be surprising that toxicologists still find novel mechanisms of toxicity resulting in previously unheard-of repercussions. To truly understand the consequences toxic metals have on our society and the individual, further research needs to be conducted, and to lessen the extent of them the public needs to be educated. There may be more to it than what first catches the naked eye.

Terminology

Heavy metals is a misleading term covering a range of metals which aren’t particularly heavy, nor particularly light. The common denominator amongst them is their toxic or poisonous effect, which is why we refer to them as toxic metals. Examples of such metals are: arsenic, cadmium, mercury and lead (ranging in atomic weight from 75-207u). The misleading term came about due to the fact that it wasn’t until the 19th century that light metals such as potassium, strontium and sodium were isolated and documented, and every metal before then was in fact quite heavy and the name was justified. Metals such as iron and magnesium are commonly found as a necessity in biological processes. The most well-known example being the situation of iron in the heme-group of haemoglobin, which allows for oxygen to be bound to the protein and for respiration to occur. Magnesium moderates a similar function in the chlorophyll molecule in plants, and the resemblance between animalian heme-group and plants chlorophyll-molecule is striking.

Mechanism

Biological processes are therefore in need of metals to some extent, however, metals which haven’t been common throughout the evolution of mankind aren’t yet integrated into our metabolism*. The upsurge in distribution of toxic metals due to both natural distribution and anthropological (man-made) distribution such as: mass-production of electronics and industrialized mining has led to unprecedented amounts of them being prevalent in our groceries and water. Toxic metals come in many shapes and sizes, as many of their chemical forms are stable and viable in nature. Some are readily excreted, and some tend to hang on to their host through bioaccumulation. Through drinking water, groceries and direct contact often connected with certain professions, the toxic metals enter our body. There, they’re absorbed as chaperones due to their close resemblance to vital molecules and readily enter our organs. Once passed through our utmost epithelial layer of cells, they may disturb many metabolic processes in vital organs - again, due to their similarity to vital organic molecules. As our metabolism is disrupted cells malfunction which often result in necrosis (tissue death) or lessened function of organs.


*Interestingly, populations where arsenic-contaminated drinking water has been present for a long period of time are more tolerant to arsenic due to a unique gene (AS3MT) capable of metabolizing arsenic to a greater extent than the rest of the population.

Neurotoxicity

Arguably, our most vital organ is our brain, and unfortunately it isn’t protected from the impact of toxic metals. Even though the effect of toxic metals on cognitive function and neural development isn’t completely mapped, some worrying mechanisms are identified. One example is that of methyl-mercury (MeHg), an organic form of mercury. MeHg is formed by microbial activity, often in aqueous environments where it’s to be accumulated readily in fish. If pregnant women eat large amounts of fish, enough MeHg is absorbed through the GI-tract and transported across the placenta to the fetus where it enters neural cells, facilitated by a mimicry mechanism through various transporters. The metal disrupts in-fetu neural development, resulting in subtle changes in cognitive functions such as IQ, memory and attention.

Possible gain

Many of the heinous consequences toxic metal entail are results of low concentration-exposure over an extended period of time and are not a result of acute poisoning. These consequences often affect major populations as they come from common sources such as drinking water, and the potential economic gain of relieving populations from the subtle impairments may be cumulatively massive. Major population may increase their economic contribution through increased cognitive and physical function and hospital bills caused by toxic metals (such as fractures caused by bone-brittleness as a result of bio-accumulated cadmium) may be reduced. Therefore, a remedy which removes toxic metals from the body would be of huge economic and humanitarian interest.

We at iGEM Lund 2019 are harvesting the evolutionary product from the world of microbes to produce such a remedy. Our efforts will hopefully result in a probiotic bacterium which can accumulate the toxic metals in your place and relieve you from the nefarious consequences briefly mentioned above.

2019-06-27

Engineering humanity

Synthetic biology is the interdisciplinary area of engineering where life is revised, updated and streamlined to fit the needs of our modern world. A majority of the conceivable and imminent inventions revolve around the exploitation of bacteria and plants - relatively simple lifeforms whose genome we’ve familiarized with and whose biological pathways we can readily manipulate. However, as the study of genomics and proteomics progresses beyond the elemental lifeforms, we soon reach the inevitable: the engineering of the human race.

Evolution

Evolution is driven by mistakes. As your genome is being copied, errors are bound to emerge in the produced sequence and mutations appear. The flawed, mutated sequence may be unsupportive of life as the disrupted codons (nucleotide-triplets coding for amino-acids) may code for essential amino-acids in a vital protein. In another outcome it may increase or reduce an individual's fitness by slightly changing the functionality of a protein, for better or worse. This minute change in fitness is what drives evolution towards a perceived goal as individuals more fit to its current environment are more likely to survive and strive. One should distinguish that evolution has no inherent goal in itself, it is simply a mechanistic progression, there is no driver nor designer pointing in the right direction. However, the change is often insignificant and unpretentious in its expression, which is why evolution works ever so slowly. Through the ages, minute changes in the genome has resulted in conspicuous structures and organisms with remarkable functions and niches. Extremophilic bacteria like Cupriavidus metallidurans and Thermus aquaticus are making us question the definition of habitability due to their ability to thrive and live in seemingly uninhabitable places, and archaea like Thermococcus gammatolerans is challenging our notion of survivability due to its ability to survive extreme amounts of radiation. The most fascinating structure of all is undoubtedly that of the brain, which ultimately has led to the development of advanced technology and culture.

Genetic factors

Evolution has laid the groundworks on which our brain is built, however we can all recognize that it isn’t the sole mechanism in charge of our cognitive capabilities. The battle between nature and nurture was one of the most prevalent scientific disputes throughout the 20th century and it is, to some extent, still ongoing. The debate has engaged psychologists, sociobiologists, geneticists, neuroscientists, philosophers, and not to forget political activists. With radical simplification applied, the two prevalent ideological camps were Social Darwinists versus Marxists, battling over determinism or lack thereof. Both extremes were indeed represented in history in the form of Nazism and Communism, both showcasing a grave lack of scientific reasoning but an ambitious amount of political trickery. Today we’ve settled dead-center. There is no biological determinism and our brain is highly plastic, however genes do affect our personality and cognitive ability in a statistical manner. The traits and abilities of identical twins are not completely identical, nor do they completely differ. Genes do affect your neural structure, but so does learning and sensory input. Culture, technology, personality and morality are all a consequence of our cognitive abilities and are therefore partly a consequence of our genes. Genetic engineering may allow us to enhance and surpass evolution and it is therefore of extreme relevance to discuss the implications which genetic engineering may have on the future of humanity.

Eradicating insanity

Many genes are identified to play a part in the development of mental illnesses and variations such as schizophrenia and bipolar disorder. These illnesses are shown to be hereditary and there is a great economic and social interest in eliminating them. But should we? Consider the amount of creative geniuses whose psychological diagnosis is that of a mentally ill, and what implications a complete removal of insanity would have on our culture. There would be no Vincent Van Gogh’s nor Charles Darwin’s nor Isaac Newton’s, nor would there be any Charles Manson’s. Do the benefits outweigh the harm done to our society, culture and humanity? It would be a mistake to befuddle the societal and individual concerns when operating on a global scale, although we shouldn’t dichotomize the two when there’s an apparent connection. Until we fully understand the underlying implications of mental illnesses (perhaps more fittingly referred to as mental variations) and the accompanying ethical concerns we should tread carefully.

Physical enhancement

It is more conceivable to imagine how the physical body may be engineered in ways with increased benefit to the individual and seemingly without jeopardizing the interests of society. Genetic predisposition for muscularity or heightened metabolism may elude you from training or a strict diet whilst maintaining a desirable physique, and who wouldn’t want that? New standards would be implemented regarding physical appearance and physical performance, but what would the aftermath be? Depending on the costs and availability, visible socioeconomic classes would arise. Companies would surely capitalize on the worldwide market, giving rise to a new form of wealth, namely health. Is a future where the discrepancy between the rich and poor is emphasized and further extended sought after? Again, do the benefits outweigh the harm done to our society, culture and humanity?

The aforementioned seemingly obvious inquiries have complicated and profound ethical concerns. Similar outcomes are to be expected when discovering the implications of synthetic biology and genetic engineering not only in humans, but also in bacteria, plants and archaea. Therefore, we at iGEM Lund are trying to thoroughly explore and recognize the ramifications of future research within the field of synthetic biology to ensure prosperity in a future of genetic engineering.

2019-06-12

Synthetic Biology, opportunities, risks and a need for change

Synthetic biology, the field of science where life is altered, modernized and reconditioned to fit the needs of today, is one of the fastest growing fields of research in the scientific community. Engineers and scientists come together to create unimaginable and awe-inspiring organic machines by simply modifying the genome of organisms in a methodical manner. But where is this research taking us? What ethical inquiries must we pose to ensure that our future isn’t ruined by our own achievements? What can we do to ensure that the research is used to maximize the goodness in the world, and not the opposite? These are questions we must answer before we continue our efforts to expand our grasp of a technology we may not be able to master.

Best to get it right

The modern era of biology has resulted in a novel field, synthetic biology, where life is engineered to suit the needs of our modern world. A standardized system of biological parts and methods has enabled engineers to create organisms with minimal effort, and it is only bound to get easier. Our rapid progression foresees a future where genetic code is transcribed, modified and produced by the common practitioner, a future where the opportunities for good are exceptional but the risk for peril inevitable. Referencing the MIT-professor Max Tegmark, synthetic biology is one of those things where it is best to get it right the first time, for there may be no second. Therefore, we must emphasize the importance of investigating and discussing the ethics, regulations and the future of synthetic biology in order to minimize the risk for disaster.

Opportunities

What opportunities may synthetic biology bring? Perhaps a more appropriate question is what won’t synthetic biology be able to achieve? Pharmaceuticals and biofuels are likely the first areas where engineered biological organisms will conquer the contemporary prevalent methods. Antibiotics and fossil fuels have showcased a lack of sustainability and we’re therefore in need of a viable solution, something that biological organisms can achieve. But inventions like these are merely scraping the utmost surface of capabilities of synthetic biology, and I urge you to delve deeper into your imagination with me.

Promising vision

Trees are wonderful creations. By adding nutrition, sunlight and carbon dioxide, they produce the most intricate and wondrous nano-structures - leaves. When the leaves fall during autumn we throw them away, and the intricate structures are gone to waste. What if we could engineer the genome of trees to grow structures which suit our needs? As autumn looms, we may be collecting computer chips, ready for use. This might seem far fetched, but hopefully it illustrates what the future of synthetic biology might hold. A world where the most absurd, bizarre and ridiculous imaginations become reality. However, there are many alternate realities where the obscure biological inventions don’t favour our wellbeing, as described in the following vignette.

Tragic vision

In your workspace there is an ordinarily-looking printer. The printer is common amongst your contemporaries and prints both ink and biological structures. A recent jogging-incident has resulted in a nasty wound-infection on your heel and you decide to treat it with a bacteria which identifies the bacteria responsible for the infection and produces specific compounds to combat it. You google your local pharmacy, enter your unfortunate accident and they provide you with a link to download. You download a genetic sequence which codes for the bacterial genome and send it to your printer, and the bacteria are readily produced. You apply the bacterial solution to your wound and one day later, the infection is gone. The next day you check your email and find one from the local pharmacy, providing you with another link to download. Odd, they never email! You press the link and the printer starts buzzing. Later that day, your town is awfully silent and panic has struck the outside world. The genetic sequence you’ve downloaded carried a deadly, airborne and malicious virus, created by a terrorist group.

Regulations

To avoid a permanent eradication of intelligent life on earth it is important for us to consider the regulations, laws and directives which need to be implemented in our future society. We must find a perfect balance between hindering the development of malevolent research and restricting honest and legitimate scientific research. To do so, we must identify what research leads to biological weapons of mass destruction and what research leads to the thriving of mankind. It is therefore infinitely important for scientists, philosophers, economists, politicians and engineers to cooperate in the endeavour of discovering what moral boundaries these laws should comply with.

Today's state of regulations on synthetic biology is scattered and incoherent whilst also being overly restrictive and too loosely enforced. The US and the EU has dealt well with the biotechnological research of the 00’s and 10’s however, an overmounting amount of research is going to leave the current state of the European and US-legislation at a loss of words. The scientific community is working fast, and the jurisdictional community therefore needs to be three steps ahead when producing regulations. Envisioning what the future might hold and how our ethics is structured is therefore a necessity when constructing the regulations.

Us at iGEM Lund are therefore in quest to raise awareness of the future of synthetic biology. We aim to discuss, educate and debate the future of synthetic biology, its regulations and ethics, to hinder the development of a future we wouldn’t want to imagine.

2019-05-07

Synthetic Biology, The era for Engineers

Biology and its subcategories have long been an area of research dominated by theoreticians and empirical research. Darwin’s vast collection of species and Mendel’s sharp and delicate experimental technique revolutionized our understanding of biology and life itself, but how can we harvest the fruit of that knowledge? How do we innovate, develop and evolve beyond nature's own interest? Synthetic biology is the answer.

The gene

The groundbreaking discovery of the gene; the unit of ancestry, evolution, and life itself, resulted in a paradigm shift like no other. This revelation was not realized in a day but was puzzled together piece by piece for nearly a century. Even though rumbling murmurs and whispers regarding the origin of life had been around for centuries, perhaps even millennia, the idea which resulted in awe was first conceived in the middle of the 19th century. It was by Charles Darwin who established the theory of evolution and Gregor Mendel who endorsed the idea of a unit of ancestry. Together, they laid the groundwork for what came to be known as the genomic era.

In the 1950s the astonishing structure of DNA, the double-helix, was imprinted on everyone's mind. Consisting only of four nucleotides, A, T, C, and G, but able to generate the diversity of life we acknowledge on earth today. These delicate coding sequences of nucleotides come together to form genes, and enough genes come together to form a genome - the recipe for an entire organism. The recipe is transcribed and translated to form proteins and ultimately a unified organism with a specific phenotype. This recipe is, however, prone to changes. As the sequences are copied, base by base, mutations are bound to occur - nature isn’t perfect. Changes are often devastating for life however, on extremely rare occasions they improve the survivability of their hosts. An antelope may run faster or a tiger may pounce more powerfully. Thus life constantly evolves for the better, it’s a constant arms race for the survival of the fittest.

The mesmerizing structure of DNA. First described by Franklin, Watson and Crick.

Controlling evolution

Researches soon realised the power of controlling evolution. What if we could read, cut and paste genes to eliminate genetic diseases or become even stronger, smarter and faster? These questions are what fueled the following 50 years of genomics. Reading, cutting and pasting was hastily achieved and the cost of such interventions has rapidly decreased since. New techniques enable faster and simpler methods of gene-editing and the area of genomics soon became approachable by members of other sciences. As engineers began adjusting to the tools of gene-editing they soon embarked on the journey towards engineering life. Genetic engineering and synthetic biology were born.

Synthetic biology

Synthetic biology is an area of research where engineering and biology are intertwined to alter existing life forms or biological organisms with the intention to solve problems or overcome obstacles. Doing so, genetic engineering plays a vital role, enabling for easy manipulation of the genome. Since engineers entered the playing field, standardized methods and parts have been created. This way, a universal language spoken amongst synthetic biologists allow for global cooperation and understanding.

Contemporary innovations in synthetic biology are strictly regulated by laws and directives from various organizations. After all, one hiccup could be devastating for life on earth as we know it. However, these constricting regulations are causing slow and limited progress, hindering the development of new radical improvements in the field. Many researchers argue that the laws are too strict and therefore cause more harm than good. Hopefully, we’ll soon see a consensus amongst scientists and the society regarding genetic engineering.

Many organizations focus on spreading awareness and an understanding of the processes that encompass engineering life in hopes to lessen the public's fear of the research. Transparency is achieved beautifully within the scientific community, albeit transparency is often disregarded when it comes to the public. Research is often communicated using a difficult lingo, excluding the layman from the conversation. This flaw should be regarded as a sin, as science should be readily available for everyone. The concept of clarity across professions is valuable for engineers as they often work cross-professionally. The scientific competition iGEM (international Genetically Engineered Machine) embodies this concept, having all of the research open-source and available for everyone.

iGEM is a competition for university students within the field of synthetic biology. The competition began in 2003, founded and hosted by MIT (Massachusetts Institute of Technology). However, it quickly outgrew MIT and became an independent organisation. In 2018 340 teams from 42 countries competed in Boston with 340 vastly different projects. Detecting doping agents in athletes, cleaning waters from antibiotics and building fungal tents on Mars, everything is showcased in iGEM.

Us at the Lund University iGEM team 2019 will be engineering a probiotic bacteria to bioaccumulate toxic metals. We’re going beyond what nature evolved these bacteria to handle, so that they can be used for more acute toxicities which endanger our health. To do so, we are using the same concepts conceived in the genomic era, but applying a methodology familiar to engineers. Our result will be a synthetic lifeform, unbeknownst to man up until now. We’re not playing God, we’re merely practicing engineering.

2019-05-01

A Brief History: Probiotics

Probiotics, an emerging field of medicine, has been praised and condemned by both experts and the public. It concerns the microorganisms interacting with you, their host, and the possible health benefits they may provide for you. As new research looms, we’re more and more certain that microbes cooperate with us in several ways. Perhaps we are the ones cooperating with them. After all, they were here before us.

The host-microbe interaction was first discovered by Antonie van Leeuwenhoek, a 17th-century working-man from Delft. Van Leeuwenhoek's meticulous artistry enabled him to produce refined lenses, allowing for the observation of microbes. Doing so, a whole new world opened up for the scientific community at the time. Biologist who had only been interested in the macro and comparatively colossal world of mammals and insects were now delving into the world of the miniscule. This was the beginning of the microbial era.

Symbiotic Evolution

The common viewpoint has long been that the microbes have adapted to us. We developed an intestinal tract and they inhabited it. However, this anthropocentric assumption can easily be rebutted by applying the simple statement: they were here before us. It would then seem illogical and unsatisfactory to believe that we developed an intestinal tract and they inhabited it. Instead, it would now seem obvious that a symbiotic and interdependent relationship developed and perhaps even with the microbes in the lead, we constructed an intestinal tract for them to inhabit. We evolved symbiotically.

This revolutionary understanding altered our perception of microbes. It would now seem inevitable that they influence us to an extent previously unimaginable. Richard Dawkins famously applied the following analogy to the relationship between genes and organisms in his book The Selfish Gene:

“We are survival machines — robot vehicles blindly programmed to preserve the selfish molecules known as genes”.

Perhaps, a similar analogy could be applied to the relationship between microbes and its host.

What do gut bacteria do?

Microbes have a wide variety of effects on its host. Some effects have even proven to be structural, aiding the development of organs. Others assist our metabolism or even protect us from pathogens. New research introduces the concept of microbes affecting our nervous system - ultimately altering our state of mind. Studies on the topic are constantly emerging and microbes will prove to interact with us in ways previously inconceivable.

Euprymna scolopes has an organ which growth is dependent on the presence of a special luminous bacteria. The organ illuminates the squids bottom, confusing predators on the hunt. Photo: Chris Frazee and Margaret McFall-Ngai

Today's market of probiotics

The main focus of the probiotic market is currently on gut flora. Having a poor gut microbiome entails health issues such as poor digestion, poor metabolism, an increased risk of heart disease and many more. Improving your gut microbiome would therefore prove extremely beneficial for your health, something companies quickly realised. What they didn’t realise was the complexity and intricacy of the several millions of interactions our microbiome has. This ultimately led to the demise of the reputation of probiotics as many of the promised effects were barely noticeable or even non-existent.

New companies focus on research-based formulas in a means to salvage the reputation of probiotics. As more research emerges, it seems clear to us that an unhealthy microbiome is a contributor to many diseases which prove detrimental for our health. Therefore, supplementing, altering or modifying the microbiome for the better could be a key factor in treating many of those diseases in a sustainable and effective way. Using solutions brought on by nature itself is often proven to be the most viable alternative, however, slight modifications for the better could improve on nature’s own system even more.

Our focus

iGEM Lund is a research team focusing on using synthetic biology to modify a probiotic bacteria to surpass natures innate abilities, something we’re very excited about.