Author: Susan

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William Gan

Complement: Past, Present and Future?

by William Gan

(Image source: Pixabay)

The immune system, the body’s defense mechanism, is what protects us against pathogenic infections. In a nutshell, it is a complex network of specialized cells and proteins that interact with one another, generating unique signals to eliminate foreign pathogens. In the world of research, immunologists are the people that strive to unravel the secrets that lurk within the many different aspects of immunity.

One of these stories began in 1891, when Hans Ernst August Buchner discovered a blood serum factor responsible for killing bacteria, naming it ‘alexin’, later renamed as ‘complement’ by Paul Erlich at the turn of the 20th century. As part of the innate immune system, complement enhances the ability of antibodies and other immune cells to clear pathogens, also playing roles in inflammation and killing of microbes.

The complement system is simply a collection of small proteins, dispersed in blood plasma in their inactive forms like mines in a minefield, waiting to be triggered by immune complexes, foreign material, damaged cells, etc. All three activation pathways in this complex system lead to the generation of C3 convertase, a protease made up of other activated complement protein fragments, cleaving C3 to make C3a and C3b.

C3b covalently binds to pathogenic surfaces, marking a target to be eliminated by phagocytes. Most importantly, it associates with its ‘maker’ to form C5 convertase that drives the terminal pathway, ultimately creating a membrane attack complex that literally rips a hole on a targeted membrane! In this chaotic cascade of protein-protein interactions, regulatory proteins exist to inactivate complement and prevent ‘unwanted explosions’, much like a dedicated bomb defusal squad.

When cells go boom! (Image source: Pixabay)

But imagine if these ‘bombs’ could somehow go rogue, perhaps through mutations that result in an altered protein function, or autoantibodies against regulatory proteins that tip the balance of complement control. The involvement of complement is the reason behind complications such as age-related macular degeneration, atypical haemolytic uraemic syndrome (aHUS) and especially paroxysmal nocturnal haemoglobinuria (PNH), characterised by complement-mediated destruction of red blood cells!

A major breakthrough in complement therapeutics came in 2007, with the release of eculizumab (Soliris), a terminal pathway inhibitor that proved to be effective in treating aHUS and PNH. However, drawbacks such as high costs and risk of meningococcal infections presents limitations to treatment but paves the way for next generation drugs like ravalizumab. C1 esterase inhibitors ie. Cinryze, Berinert and Ruconest, function to completely switch off complement and are currently used to treat hereditary angioedema.

The therapeutic landscape is constantly changing with the many possible innovations to improve future therapies ie. alternate drug administration routes, physiological barrier crossings, etc. But in the end, complement-mediated diseases constantly beg the question of the level of inhibition required, raising much interest as an ideal therapeutic choice. By modulating and reducing complement activity rather than turning it off, homeostasis could be restored thus treating disease while simultaneously maintaining the role of complement in immune defense!

 

Inspired by my final year research project and this simple, easy-to-understand video on complement:
https://youtu.be/BSypUV6QUNw

Compendium of current complement therapeutics. (Newcastle researchers involved!) –
https://www.ncbi.nlm.nih.gov/pubmed/31446305

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Liza Olkhova

Unhealthy diet leads to a higher risk of death and disability than tobacco smoking

by Liza Olkhova

Image source: Pixabay

It is no longer surprising to hear that diet is just as important as lifestyle choices we make that determine our quality of life and longevity. With obesity levels rising globally, higher death rate and disability rise alongside this. An urgent need to raise awareness regarding imbalanced and damaging diet choices in children and adults is required in order to tackle this global problem and reduce its socio-economic impact.

More evidence comes to light to unequivocally support this notion from decades-long extensive study. A Lancet article published in April 2019 summarises a global study conducted worldwide in 195 countries from 1990 to 2017. The study assessed what risks are associated with lifestyle choices including suboptimal diet and tobacco smoking, alongside major diseases such as cancer.

It turns out that high blood pressure is the biggest killer with over 10 million deaths per year attributed to hypertonia. On the second place, however, is diet-related death with almost 9.5 million deaths per year. Surprisingly, tobacco smoking came third following diet.

Diet-related death is most commonly caused by cardiovascular disease, cancer and diabetes that have developed as a result of poor diet choices. For instance, high sodium content, consumption of red meat, processed food and sugar-packed beverages as well as low intake of health-boosting foods such as grains and fruits all attributed to the majority of death and disability cases.

How can we move away from this problem? Extreme changes to the diet in many countries have to be made on the national level, but of course, on the global level too. This includes education of children and public through campaigns, policy reforms to provide appropriate food labelling and price regulation, implementation of balanced diets in schools and universities, changes in taxation of various products (such as a recent ‘sugar tax’ in the UK on high-glucose drinks).

There is also evidence that substituting meat protein with plant-based protein source reduced the level of cardiovascular disease. Therefore, it could be worth letting people know about the healthy alternatives to their current diets instead of notifying them of what is unhealthy.

 

Read the Lancet article in full: https://doi.org/10.1016/S0140-6736(19)30041-8

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Annie Derry

Prioritising sleep is much more important than you think

by Annie Derry

Prioritising sleep is much more important than you think

A really good 7- or 8-hour sleep seems elusive for many people in the working world. A lack of sleep is sometimes even bragged about as if being ‘too busy’ to sleep equates to success. In our fast-paced environment with constant work, endless Netflix series to binge-watch, and phones that we never put down – it is easy to see why it’s harder than ever to get some shut-eye… or any peace for that matter.

In his recent TED Talk, “Sleep is your superpower” and his popular science book “Why We Sleep”, Professor Matthew Walker from University of California, Berkley, hones in on the benefits of having good ‘sleep hygiene’, and the sometimes-detrimental effects of lacking it.

Image source: Pixabay

Throughout the day our bodies work tirelessly at a molecular level to keep us moving, working, thinking, breathing – living. There is a constant stream of reactions going on that allow us to do this. A lot of these reactions produce chemical by-products along the way, which can be harmful if they are not removed. During the time that we sleep, one of the many activities going on in the brain is the removal of these waste products, in a sort of cleaning process that ‘washes’ the brain. Along with this, sleep is important for the consolidation of connections between neurons, allowing information from the previous day to be processed and stored.

What are the effects when these sleep tasks cannot be carried out?

Late nights; at your own risk:

1.Cognitive ability and memory function

It is fairly common knowledge that our higher cognitive processes are impeded on the day after a poor night’s sleep. Sleep deprivation has been found to impair attention and working memory, as well as long term memory and decision making. Prolonged wakefulness decreases alertness and ability to concentrate through the fact that it causes slowed responses and lapses – brief moments of inattentiveness. This is one of the reasons why driving a car or taking an exam with a severe lack of sleep is generally a very bad idea.

2. Long-term disease risk

In recent years there has been a growing link between a lack of sleep and the protein implicated in Alzheimer’s Disease, beta-amyloid. A build-up of this protein has been found in Alzheimer’s patients and, independently, in people reporting sleep disorders. It is thought that a lack of sleep contributes to a vicious cycle, where the brain is less able to wash out toxic proteins like beta-amyloid, as it usually does this during non-REM sleep. This could therefore contribute to the increased levels seen and lead to disease progression.

3. Higher risk of cardiovascular problems

There were some alarming results in a study which monitored the effects of losing an hour of sleep when the clocks go forward in the Spring (Daylight Saving Time, DST). Researchers found that the incidence of heart attacks reported by hospitals increased by 24% in the days following the time change. The opposite effect is seen when we gain one hour of sleep as the clocks go backwards in the Summer – the number of heart attacks reported decreases by 21%.

4. Immune function

Some of the most eye-catching statistics from Matthew Walker’s research were from his studies into the effect of sleep on our immune system. We have a number of cell types that all work together in order to fight off infection by recognising and killing foreign microorganisms like bacteria and viruses. Among the cells that are important in this, the natural killer cells (NK cells) are vital in the process eradicating threatening microbes. It was found that when sleep was reduced to 4 hours, even just for one night, there was a 75% reduction in NK cells in the blood of patients the next day. This indicates at least an association between our sleeping habits and how well we could fight off an infection, even a common cold, if exposed after a poor night of sleep.

 Don’t panic

Studies in to sleep do have alarming conclusions sometimes, but we cannot assume that sleep is the isolated causative variable contributing to the negative effects seen. As with almost all studies they must be taken as an indication, rather than a conclusive result. It also must be considered that some people may be genetically (or otherwise) predisposed to restless nights of sleep – we cannot assume that one person needs exactly the same number of hours to see out a healthy life.

That being said, it wouldn’t do any harm to try and pay more attention to the needs of our body and to allow ourselves to sleep as much as we really need to.

How to prioritise getting more/better quality sleep?

  • Reducing screen time at night
  • Reducing artificial lighting in the bedroom
  • Using apps like Headspace in order to practice mindfulness (and as a useful tool to get back to sleep if you wake up in the night)
  • Reading before bed to help to wind down
  • Going to sleep and waking up at a similar time every day

FYI… Matthew Walker received his PhD in Neurophysiology at Newcastle University in 1999.

This blog post was based on:

“Why We Sleep” – Matthew Walker

“Sleep is your superpower” – TED Talk by Matthew Walker

https://www.ted.com/talks/matt_walker_sleep_is_your_superpower?language=en

Sleep deprivation: Impact on cognitive performance – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2656292/

 

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Liza Olkhova

How can the past experiences of your ancestors can alter the way you behave and your gene expression?

by Liza Olkhova

Photocredits: Pixabay

Epigenetics – the study of how gene expression is altered without altering the gene sequence itself – may hold the key to how gene expression can be modified in the offspring of parents exposed to environmental factors such as severe stress, without offspring being exposed to the same factors. This can revolutionise the way we assess and deliver children healthcare

Gene expression regulation depends on various chemical modifications of the genetic code without alteration of the code letters themselves (mutations). Various chemical modifications of genes can either facilitate or hinder gene expression by altering the amount of protein synthesised from a gene.

So the question is, can these gene chemical tags be passed down to the next generations?

It has been shown that they are wiped out in egg and sperm cells, however small non-coding RNA (sncRNA) may be present in sperm and may affect the regulation of RNA levels in zygote and the developing embryo. Moreover, sncRNA molecules can be modulated by stress.

How could the trans-generational changes induced by stress be modelled in vivo? To answer this question, various mouse models were developed, in which mice were subject to stress. Surprisingly, changes in the RNA dynamics were passed on not only to the first generation of offspring, but also to further generations. These gene expression changes were accompanied by behavioural abnormalities, for example, more risk taking behaviour. Rodent behaviour was tested using a specially designed maze that assesses rodent exploratory behaviour.

The next aim is to explore how changes seen in sncRNA molecules in rodent models could be compared to changes in human physiology. For instance, a study involving analysing blood samples of soldiers before and after deployment showed increased levels of different types of sncRNA molecules with some of them correlating to post-traumatic stress disorder (PTSD).

Currently, the science is at the dawn of fully understanding epigenetic changes within human genome and how these changes could potentially be transmitted through to further generations. We have yet to witness more detailed and advanced human studies in order to gain a clearer perspective.

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Emma Kampouraki

Biology: significantly more efficient than technology

by Emma Kampouraki

Photo credits: Biohm (https://www.biohm.co.uk)

For thousands of years, the only true driving force of life on Earth has been evolution. Among the population of every species, only those with the strongest characteristics survive, leading them to selectively pass on these characteristics to their ascendants, in an attempt to adapt better to the changing environment.

Humans, having evolved as a result of the same process, are now taking nature as an example for the construction of their own habitat. Recently, I had the opportunity to meet the Founder and Director of Innovation at Biohm in a Pint of Science event. Biohm could – and may – have been derived from the combination of bio and home; otherwise construction using natural materials. Mostly considered as waste nowadays, organic matter is well re-used in nature, through a process facilitated by decomposers; organisms that break down dead or decaying organisms, absorbing nutrients for their own growth and development. Could we do the same with our homes?

Ehab Sayed from Biohm says yes. The company collects organic waste and holistically sustainable natural materials (which sometimes include organisms, for example fungi) and turns them into building materials, which are satisfactorily durable and stable for a number of years before they are replaced (for free) with new ones. Durability is mainly down to the specific material or mixture of materials used, and stability depends on the particular structures constructed. Their novel and revolutionary construction system is called Triagomy and is basically the way they assemble the materials together which gives them great stability and the ability to be self-assembled. The team consists of researchers, engineers, architects and experts in circular economy and sustainability. The perfect blend for green buildings and the advent of the recycled construction industry.

If we can convince ourselves to think out of the box, use what we have effectively and respect the environment as a priority, we will ultimately facilitate and speed up evolution in our own habitat. Evolution will bring growth and better adaptation. More importantly, it will solve the problems of plastic pollution, waste management, toxic construction materials and deteriorating health in Earth’s ageing population.

 

Declaration: This is a non-sponsored blog, inspired by a novel idea for a circular economy and recycle, facilitated by scientific knowledge.