Hello, my lovelies!

We are fast approaching the end of the first month of January! How have those new year resolutions been going for you so far? Not great? Don't worry, everybody hits a few bumps in the road. So what you haven't done your morning exercises for a week or perhaps you haven't started learning that new language, what is a week in your entire life. You are allowed a day off, whatever you need to get back into achieving what you know you can achieve. 

'In order to succeed, we must first believe that we can.'  
- Nikos Kazantzakis

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Invasive species are costing the US economy a minimum of $42 billion in damage each year. Infectious diseases transmitted by vectors are responsible for 1 million deaths annually, many being children. Global food productivity is threatened by pests and competing plants developing resistance to insecticides and herbicides. Scientists are now casting their eyes to a possible solution that tips the laws of genetics in favour for a gene engineered by scientists. Such a technique could play a role in the conservation of endangered animals, eliminating diseases transmitted by vectors and reversing resistance to herbicides or insecticides. Gene drives hold the ability to save a species or wipe out populations. Have we gone too far?

What are gene drives?

Gene drives are the next big thing in the wonderful field of Genetics. Essentially with the help of CRISPR Cas9, this genetic engineering method provides a novel way of tackling both environmental and public health issues, but how? Essentially, a gene coding for a particular trait this could be advantageous or disadvantageous (depending on whether you was to ‘save’ or ‘destroy’ a population) is introduced into an organism.

Gene drives are carried out on sexually reproducing organisms, this poses a problem to geneticists. The engineered gene drive trait has a 50/50 chance of being passed onto the offspring. Sadly this is the awkward and inconvenient truth of sexual reproduction, resulting in the engineered gene being expressed in very few individuals - the opposite to what they want to achieve. This challenge was overcome by modifying the chosen gene to act ‘selfishly’, thereby ensuring it is expressed in a larger proportion of offspring. This can be done in one of two ways.

During embryo development, one trait is chosen from either the maternal chromosome or the paternal chromosome and that is the one that is expressed e.g. brown eyes from your dad. This is avoided by the engineered trait copying itself onto both chromosomes so either way, you get the same outcome! Or, molecular biologists can ensure that the competing trait proves deleterious and results in lower viability for those inheriting it. Either way, the end product is the desirable gene increasing in frequency and spreading through the population like wildfire.

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There are two forms of gene drives seeking to achieve different outcomes: Modification and Suppression. Modification gene drives aim to ‘save’ populations by spreading desirable traits through a population. Typical gene targets for Modifying gene drives include ‘blocking pathogen development’ or ’increasing survivability’. Suppression gene drives aim to reduce/eliminate populations as such the genes targeted often provide no fitness benefit to the chosen organism including ‘reduced life spans’ and deliberately introducing a bias to ‘sex ratios’.

Potential role in Conservation:

Gene drives provide the opportunity to spread advantageous traits such as resistance to a species-specific disease. This is where engineering trumps mother nature, as the gene for disease resistance spread through the population at a faster rate compared to the long hauled process of natural selection.  

Globally, populations of amphibians are declining at an accelerated rate due to Batrachochytrium dendrobatidis otherwise known as the chytrid fungus.  How the chytrid fungus causes such high mortality remains a bit of mystery, however, it has been shown that it can disrupt an amphibian's skin. Many amphibians breathe through their skin, as such, any disruption in the epidermal layer can cause the amphibian to suffocate. Implementation of a modified gene drive may avoid future localised extinctions.

Alternatively, gene drives could aid the fight against invasive species. Invasive species have adverse effects in the areas ecology as well as the economy, this has lead people to take drastic action to mitigate against further losses.  A gene rendering a species vulnerable to a species-specific molecule (a poison or a disease) could aid in kerbing an invasive species populating growth. Such approaches are increasing in popularity due to their minimal ecological impact.

The Potential role of gene drives in disease management:

Vectors are organisms that are capable of transmitting a disease or parasite from one animal or plant to another. Common vector-borne diseases include Malaria, Chikungunya, Chagas Disease, Plague and the Zika Virus. The Anopheles genus of mosquito is perhaps one of the most famous vectors, responsible for the transmission of Malaria, Dengue Fever and Zika virus.

There have been small successes in the production of genetically engineered dengue-resistant mosquitoes, however, these mosquitoes were later found to be resistant to one subtype of dengue fever. Nonetheless, tests remain promising.   Scientists are focusing their efforts on the Anopheles that is responsible for transmitting Malaria. Malaria claims the lives of 650,000 people each year, so the need for a solution is high.

Geneticists begin by looking for a target of which to base the gene drive on, in the case of combating infectious diseases the aim is to reduce the transmission rates. Two genes instantly drew attention including the AKT transgene found in the midgut of the mosquito and the single chain antibody located in the salivary glands. The reason why these genes are receiving all the attention becomes clear when looking at the life cycle of Plasmodium (the microorganism responsible for the onset of Malaria), the image below shows the life cycle.

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The midgut of the Anopheles mosquito provides the optimal conditions for the Plasmodium gamete to become an oocyst. Once the oocyst has been formed it bursts, releasing loads of sporozoites that migrate from the midgut straight to the salivary glands so that they are successfully passed on with the Mosquito's next blood meal. The aforementioned genes play a vital role in providing an opportunity to block pathogen development or block the Mosquitoes ability to become a vector.

Limitations of gene drives:

Firstly, gene drives require the genetically engineered organisms to have many generations in order to spread through the population. Therefore, the time lapse between release and successful spread through a population depends on multiple factors of the vectors biology such as the time needed for each generation, the impact of the gene drive on individual fitness and their mating system dynamics.

When manufacturing a harmful trait to be used for a gene drive, it must be made deadly but not too deadly… Anything too deadly will result in the engineered organism dying well before they manage to pass on the trait to their offspring.

Evolution is working against you...  Gene drives work on the basis of introducing harmful traits and ensuring that they spread through a population like a wildfire. However, evolution by natural selection works on the basis of favouring individuals with advantageous traits and dooming the individuals with deleterious ones. Therefore, it is very likely that through the duration of the gene drive natural selection will lead to one organism acquiring resistance to the harmful trait and thus will be favoured, making the efforts of the gene drive obsolete.

Overall, this is an exciting field of genetics whether it be for agriculture, conservation, or for health purposes. With the development of CRISPR Cas9, it is plausible that further research into Gene Drives may well lead to them becoming a viable option in future. Is this a step too far? Or a natural progression to a solution for a long-standing problem?

Science in the City

xoxo

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Topaz

 Welcome back!

I hope you have all had an amazing week. As you may or may not be aware there is a cold snap sweeping across the Uk and parts of Europe if that is you make sure to keep warm! Let's start this weeks post. 

They are responsible for a whopping NZ$3.3 billion loss in productivity each year and listed as one of the biggest threats to marine and terrestrial biodiversity. They are the Invasive Species. In light of the economic and ecological destruction caused by these invaders, James Russell and New Zealand are taking a stand. Desperate times are calling for some desperate measures. They have called for a mass eradication of all invasive mammals by the year of 2050 to preserve endemic wildlife. Is this extreme? Or, is this necessary?  

2015, marked the year where tourism became one of the most profitable industries above agriculture for New Zealand. This island boasts the last surviving species of Tuataras an order of reptiles that thrived in the age of the dinosaurs (top left). Not a reptile person? How about catching a glimpse of four species of Amphibians that are so ancient they have changed very little in the past 70 million years: the Pepeketua (bottom left). For those birdwatchers, the Island is known as the ‘seabird capital’ and home to the Kiwi! Truly a nature lovers paradise.

Invasive species pose a significant risk to this island’s biodiversity thereby posing a threat to their economy. In 2005 the IUCN found that over half of animal extinctions were caused by the presence of invasive species. New Zealand has already lost three of its endemic frog species due to the introduction of rats.  New Zealand aims to avoid further extinction by ordering an island-wide cull of invasive mammals. Take a look at the three invasive species that have earned the top three spots on New Zealand’s Hitlist!

The fight arrives in your own backyard… literally:

This extreme Conservation project will not be easy to carry out, the first issue arising is the sheer scale of this project.  Eradication projects such as this are not unheard of and actually boast high success rates but these have been on islands with an area of 128 square kilometres, New Zealand has a total area of 268,000 square kilometres.   

In addition to this, New Zealand’s dynamic landscape includes cities, forests and farms. Such differences in landscapes offer a multitude of safe havens for the top three on the island’s Hitlist. For this project to be successful, traps would have to be placed in people’s  back yards, as such the people of New Zealand must be behind this project 100% as anything less could lead to areas becoming refuges for invasive mammals. Turns out, the public is fully supportive of this mass cull. With support from the public, conservation groups and the government it seems the end of the line is near for New Zealand's Invasive mammals. Bad time to be a possum in New Zealand... or a rat... or a stoat.

Alright, so they have the support of the masses but how is the killing part going to carried out? After all, they are upscaling. The answer to that question is… they are not quite sure, there are a few methods in the pipeline such as:

Poisons: Always a good option when it comes to pest control. A common one being 1080 (sodium fluoroacetate) for killing rats. Drawbacks for this particular poison is that it also kills the endemic Kea bird.

Traps: Another familiar pest control method. Goodnature manufactures a trap that crushes the skulls of rats and possums. Clean up is free as the carcases are usually eaten by local cats… eww.

Not techy sounding enough? Well, how about using drones fitted with biosensors that ‘locate’ hot spots of invasive mammal activity and then drops poisons on the area? Still not impressive enough, well perhaps the use of genetic biocontrols will do.

Genetic biocontrols also referred to as Gene Drives are a really nifty bit of science. Using CRISPR-Cas9 scientists can introduce deleterious traits that will lead to suppressing the population of the invasive species. According to Ethan Bier a geneticist, once introduced the 'harmful trait can go from 1% to 100% in the span of just 10 generations'. Common targets for this approach are genes related to survival and reproduction.

Combating Invasive Species in the Future:

Invasive Species have infiltrated many continents and this is facilitated by the increase in globalisation and environmental changes. Rapidly changing climates allow for species to succeed and become established in areas they would normally perish in.

Britain has been invaded by a variety of species whether they are introduced accidentally or deliberately (as a biological control for some other pest). BBC has shortlisted the UK’s most invasive animals featuring the Himalayan Balsam that costs the UK economy £150 million a year, the American Mink originally brought over for the fur trade has now been implicated in the dramatic declines of water voles. The list continues.

New Zealand’s public has rallied in support of preserving their island's wildlife, and even though they are somewhat resistant to genetic biocontrols they are more than willing to kill in the name of conservation. With British Invaders wreaking havoc on our economies and nature it begs the question: Are we willing to kill to save our wildlife?

That is all, for now, guys! Thanks so much for reading and have an awesome weekend. 

Science in the City

xoxo

Literature:

Brian Owens. The Big Cull. Nature. 451, 7636 (2017).

Regan Early, Bethany A. Bradley, Jeffrey S. Dukes, Joshua J. Lawler, Julian D. Olden, Dana M. Blumenthal, Patrick Gonzalez, Edwin D. Grosholz, Ines Ibañez, Luke P. Miller, Cascade J. B. Sorte & Andrew J. Tatem. Global Threats from invasive alien species in the 21st Century and national response capacities. Nature. 7 (2016).

Image references:

Norway Rat, Stoat, Australian Brushtail possum, Tuatara, Pepeketua, Kiwi, Kokako.  

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Topaz

Hello, all you lovely Science lovers! 

Do you love the new blog as much as I do? New Year and a brand New Blog all for you, my faithful readers. As I have not said it officially yet HAPPY NEW YEAR! I will not keep you waiting let's head straight into it. 

1 in 5,000 newborns will have an enlarged liver and spleen. The cruel reality of the diagnosis becomes clear, this newborn has one of the 50 conditions known as Lysosomal Storage Disorders (LSDs). LSDs are relatively rare genetic disorders, carrying a life sentence filled with complications for the body's respiratory system, skeletal system and Central Nervous System. Rare as they are, certain forms of LSDs will lead to some Children not living to see their 5th Birthday. There is no cure. Initially, the only options of treatment were blood transfusions and very risky bone marrow transplants, researchers are now focusing on treatments that tackle the source of this disorder.  

Before we begin our journey we must first familiarise ourselves with the organelle at the heart of these disorders: the Lysosome. Lysosomes are small spherical structures found in the majority of animal cells, in spite of their size they play a significant role in cellular recycling and the overall maintenance of the cellular activity. They contain digestive enzymes that are able to ‘digest’ external biological substances (such as bacteria) and recycle components from formerly defective proteins as well as other compartments of the cell.  

Based on how essential lysosomes are in the upkeep of a functioning cell they have caught the attention from the medical field. For years clinicians have been activating autophagy (where molecules and other defective organelles are taken to the lysosome for digestion) with a chemical known as TFEB. This chemical leads to the production of more cellular lysosomes and stimulation of autophagy, such responses show potential in the treatment of Parkinson's disease, cancer,  obesity and even the removal of certain pathogens (bacteria and parasites).

What leads to the onset of LSD? It all starts with a substrate (a molecule that binds to an enzyme) as an example let’s focus on Gaucher's disease (most common LSD). The onset of this disease begins when a fatty substrate known as Glucocerebroside is manufactured in the cell, once this substrate has fulfilled its destiny within the cell it begins to make its way to its final destination - the lysosome to be degraded and recycled for future use.  

However, this all depends on whether the enzyme Glucocerebrosidase is present. In the absence of this enzyme, the substrate Glucocerebroside begins to accumulate and as we know too much of one thing is never too good. This accumulation of the substrate eventually reaches toxic levels, thereby triggering the onset of the characteristic symptoms of Gaucher's disease. If you're wondering why Glucocerebroside cannot be degraded by any of the countless other enzymes present in the lysosome, the answer would be the ‘intimate’ relationship between an enzyme and its substrate.

The image below summarises how enzymes actually work in the body, similar to a lock and a key, one enzyme fits one substrate (on most occasions anyway).

All 50 LSD’s share similar developments, the only thing changing would be the substrate and the enzyme involved.

There is no cure for LSD, however, there are now several possible treatment options. For this post we are going to focus on two that aim to reduce the levels of substrate accumulation:

ENZYME REPLACEMENT THERAPY:

Perhaps after reading how LSDs develop you may have reached an assumption that a possible treatment would be to replenish lysosomes with missing enzymes or replace defective enzymes with a functional version. If so… you have just described Enzyme-replacement therapy!

This treatment option have shown to be effective in reducing spleen and liver size, alleviating anaemia ( deficiency of red blood cells or haemoglobin) and thrombocytopenia (a deficiency in platelet numbers).However, this therapies success is limited due to its inability to distribute itself to several other body parts triggering Osteonecrosis, Osteopenia and Pulmonary Hypertension. Nonetheless, the greatest shortfall would be the inability to pass the blood-brain barrier providing little relief of neuropathological symptoms.

SUBSTRATE REDUCTION THERAPY:

This is where Substrate reduction therapy comes in. This treatment option does not attempt to replace enzymes, instead, it seeks to interrupt the synthesis of the substrate in the first place. This therapy is favourable to some as it is given orally and rarely triggers an immune response. Interestingly, this therapy works similarly to statins, these are prescribed to patients to lower their blood cholesterol by inhibiting the enzyme responsible for producing the cholesterol.  

Substrate reduction therapy uses a group of molecules known as imino sugars. Imino sugars work by inhibiting the enzyme responsible for synthesising the substrate. Additionally, the molecules used in this form of treatment may be small enough to penetrate the blood-brain barrier offering relief where Enzyme-replacement therapy could not. Side effects remain to be a slight problem with tremors and fevers being among them.

NEW HORIZONS FOR NEURODEGENERATIVE DISEASES:

I really enjoy the research stage for each of my posts mainly because I love learning about aspects of Biology I have not come across before. Out of everything that I read for this post I found the overlap between LSDs neurological symptoms and other neurodegenerative diseases fascinating. There is a form of LSD called Niemann - Pick type C that is also termed Childhood Alzheimer's based on the similarities in pathology and symptoms.  Both have triggers routed in the accumulation of cholesterol in the neurones of the brain.

Sadly, the life expectancy for patients with this form of LSD is 20 years old. What fascinates me is that LSDs are rare but there should be so much more research into these disorders. They offer a rare opportunity to look at neurodegenerative disorders differently and perhaps reach new forms of treatment.

That bring us to the end of this post! I hope you have enjoyed it and more importantly that you have gained a little bit of new information on these relatively rare genetic diseases. Have an amazing week guys the aim it to have a new post on this blog every Friday or Saturday. Stay safe from this freezing weather until next time.

Science in the City

xoxo

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Topaz