#7 Never Feel Pain Again, Increasing Plastic Eaters and the Dark Side of the Genome.
A microbe that has potentially solved and counteracted the feeling of pain, an increase in plastic eating enzymes and the utilisation of the dark genome.
🦠Microbe That Solves Pain?
A dangerous microbe that may offer a new way to silence pain…
Whilst the anthrax bacterium has been used as weapon and scare tactic for many years, there may be a more beneficial and unexpected function. One of the toxins associated with the bacterium may be able to “silence” multiple types of pain in animals.
The anthrax toxin works through mechanisms of signalling in neurons within the central and peripheral nervous system. The central nervous system consists of the brain and spinal cord controlling most of the functions of the body and mind. The peripheral nervous system therefore contains the nervous system that lies outside of the central nervous system. The research team revealed that this specific anthrax toxin works to alter signalling in the pain sensing neurons, with this being delivered in a targeted manner into neurons of the CNS and PNS, demonstrating that it could offer relief to animals in distress.
To further their research the team combined parts of the anthrax toxin to varying types of molecular cargo to deliver to the pain sensing neurons. This means that this technique can be used to design novel precision pain treatments that act within a specific and defined location such as pain receptors, without the widespread systemic effects of current pain-relief drugs such as opioids.
The senior investigator Isaac Chiu stated that “This molecular platform of using a bacterial toxin to deliver substances into neurons and modulate their function represents a new way to target pain-mediated neurons.”
However, there won’t be drugs on the supermarket shelves tomorrow making you invincible… The need to expand the current therapeutic arsenal for pain management remains acute, said the researchers. For the moment, opioids remain the most effective form of pain medication. Opioids are medication that act on opioid receptors to produce morphine like effects. These substances are primarily used for pain relief such as anaesthesia.
Chiu went on to say that “There's still a great clinical need for developing non-opioid pain therapies that are not addictive but that are effective in silencing pain”. The teams research and experiments into this area show that there is at least one strategy that could be used to target pain neurons using a bacterial toxin. The team emphasise that this is purely experimental and significant further testing would need to occur before this technology was implemented into the real world.
In some of the teams experiments, they found that the anthrax bacterium toxin altered signalling, as previously mentioned, in both dishes and living animals. Injecting the toxin into the lower spines of mice, produced pain silencing effects. These prevented the mice from sensing high-temperatures or mechanical stimulations. Interestingly and importantly, vital signs such as heart rate, body temperature and motor coordination were not affected by the introduction of the toxin. This lack of widespread effect is key for future applications in more targeted approaches.
Furthermore, the injection of the toxin into the mice alleviated the symptoms of two other types of pain. Those being inflammation based pain and nerve cell damage based pain. These are often seen in the aftermath of more traumatic injuries as well as viral infections such as shingles, or complications of cancer treatments. Moreover, the researchers observed that as pain diminished, the treated nerve cells remained physiologically intact, this finding indicated that the “pain-blocking” effects was not due to the direct injury, but rather stemming from the altered signalling inside them.
The final step of the Harvard teams research involved the designing of a carrier vehicle from anthrax proteins, they used it to deliver other pain-blocking substances into nerve cells. This approach, also blocked pain in mice. These experiments demonstrate how this could be part of a novel delivery system for targeting pain.
A few final questions and warnings were raised. Firstly that as work progresses the safety of the toxin treatment must be carefully monitored. The interesting question within the world of evolution - why would a microbe silence pain? As well as this, what other applications could there be? Could this be a key part of the future of targeted treatments?
🗑️Plastic Eaters Increasing?
Plastic Eating Enzymes May Be Increasing Due to Pollution…
Microbial enzymes are key to all life as we know it. However, the number of these microbial enzymes with the ability to degrade plastic is growing in correlation to that of plastic pollution. This conclusion has been drawn by a Swedish University team that has measured samples of environmental DNA from across the globe.
The problem of plastic pollution is rapidly growing with levels increasing from 2 million tonnes a year to 380 million tonnes a year over a 70 year period. Due to the dramatic change in levels as well as the time period, there has been sufficient evolutionary time for various microbes present in the environment to respond to these compounds and for different enzymes to develop. Over a variety of recent studies, different enzymes have been discovered to degrade different plastics with the variety increasing year on year.
The research team analysed hundreds of samples from hundreds of locations across the world. They used computer modelling to search for microbial enzymes with plastic degrading potential. To test for correlation they cross referenced the official numbers for plastic waste across counties and oceans with the environmental DNA samples. The team stated that “Using our models, we found multiple lines of evidence supporting the fact that the global microbiome's plastic-degrading potential correlates strongly with measurements of environmental plastic pollution – a significant demonstration of how the environment is responding to the pressures we are placing on it.” This therefore supports the idea that there is causality as well as correlation between the two factors.
In total over 30,000 enzyme homologues were found with the potential to degrade 10 different types of commonly used plastic. Some of the noted locations with some of the highest amounts of plastic pollution were samples from the Mediterranean Sea and the South Pacific Ocean. Currently very little is known about these plastic degrading enzymes. The team went on to say that they did not expect to find such a large number of them across so many different microbe communities and environmental habitats. This shows the extent of the anthropogenic pressure being enforced onto the environment and natural ecosystems.
A microbiome is defined as the entire set of microbes present in a specific environmental location. The plastic degrading enzymes which the researchers found were widely distributed across both the ocean and soil microbiomes. They reported large amounts of variation encountered in the number and type of plastic particles, as well as plastic degrading enzymes.
One clear example of the correlation and believed causality between the two factors is that of a few of the land samples. The land samples contained significantly more phthalate based plastic additive compounds. These are a common compound used in a variety of products and goods. They are however known to be especially susceptible to leaking during production, disposal and recycling - processes that normally occur on land. Resultantly there were a higher level of enzymes that were able to degrade these types of plastics and compounds and so indicating the connection.
Similarly in the ocean environment, it is reported that enzymes with degrading capability increased with depth. The dataset involved 67 locations and showed consistent recordings of higher degrading enzymes at deeper levels. This further indicates a connection as over past years higher levels of microplastics are recorded at lower depths.
Turn To The Dark (Genome) Side?
Recently evolved “Dark Genome” offers clues on how to develop treatments…
Firstly, what is the dark genome? Previously termed “junk DNA” it is a contentious area among biologists. The human genome contains over 20,000 genes, we know that these vital regions of DNA equate to less than 2% of the total. Therefore the dark side of the genome, accounts for 98.5% of genomic space where repeat elements, enhancers, regulatory sequences and non coding RNA reside… Yet this is perhaps the first time many will have heard of it. Very little about the function of regions of DNA within the dark genome are known.
A Cambridge led team recently discovered that proteins are produced by over 248,000 regions of the “dark genome” and are linked to multiple diseases. Furthermore, new proteins arising from recently evolved regions of the dark genome could be used in the diagnosis and treatment of a few diseases such as schizophrenia and bipolar disorder.
Schizophrenia and bipolar disorder are mental disorders renowned for being hard to distinguish, diagnose and treat despite being one of the most heritable mental health disorders. The research team say that the new proteins could be key biological indicators to distinguish between the conditions and to help identify patients more prone to psychosis or suicide. Scientists think that the hotspots in the dark genome associated with the disorders may have evolved because they have beneficial functions. Their disruption however by external and environmental factors lead to susceptibility or development of schizophrenia or bipolar disorder.
Dr Prabakaran said that “By scanning through the entire genome we’ve found regions, not classed as genes in the traditional sense, which create proteins that appear to be associated with schizophrenia and bipolar disorder,”. He went on to say how this discovery opens up numerous possibilities in terms of druggable targets due to the fact that no one has ever looked beyond our genes for clues in understanding these issues.
The researchers believe that these genomic components of schizophrenia and bipolar disorder are specific to humans and that these newly discovered regions are not found in other vertebrates. It is highly likely that the regions evolved at a faster rate due to more advanced cognitive abilities in humans.
The first author of the study at Cambridge said that “The traditional definition of a gene is too conservative, and it has diverted scientists away from exploring the function of the rest of the genome. When we look outside the regions of DNA classed as genes, we see that the entire human genome has the ability to make proteins, not just the genes.”
Off the back of this discovery Prabakaran left his position at the University to create the company NonExomics in order to commercialise this and other discoveries. Seed funding has been raised to develop new therapeutics that will target the proteins implicated in schizophrenia, bipolar disorder and other diseases.
Weekly Topics
🏞️ Environmental
Iodine in desert dust destroys ozone
Proactive conservation of New Zealand whales
Tracking of nearctic seabirds surprises scientists
🐼 Conservation
Unprecedented fires in Madagascar threaten lemurs
Ecological dependencies make remote reef fish communities vulnerable to coral loss
Southeast Asian protected areas are effective in conserving forest cover
🦠 Disease and Illness
Gum disease increases the risk of other illnesses
😷 COVID
Management of COVID-19 patients with chronic liver diseases
People with Omicron less likely to be hospitalised
The year of coronavirus variants
🧪 Biochemistry
Pop up electronic sensors could detect when individual heart cells “misbehave”
Scientists develop forensic method to identify humans using hair proteins
A superstar enzyme is ready for its close up
🔬 Evolution
Engineering models better explain the patter of nature
New insights into when modern mammals evolved
5 Ice age mammoths unearthed in the Cotswolds
🧬 Genetics
Favourite genetics stories of the year…
Finding unknown species in the genomes of extant species
50 years ago scientist genetically modified mosquitos
📷 Weekly Camera Roll
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