Category: Annie Derry

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.

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/

 

by Annie Derry

Deoxyribonucleic acid (DNA) is the backbone of the natural world and the molecule which encompasses all of the information needed for the survival of most living organisms. It exists at its most primary level as a series of nitrogenous bases within nucleotides, of which there are 4: Adenine (A), Thymine (T), Cytosine (C) and Guanine (G). These 4 bases form hydrogen bonds with one another in particular patterns; A pairing with T, and C pairing with G, to form the double helix structure that is associated with the DNA molecule as a whole. It’s rather incredible that the information needed to grow and maintain a living organism comes down to 4 nitrogen bases.

Imagine what could be done with 8 letters; 8 bases.

This is what a group of researchers from various US companies and institutions have managed to create: eight-letter DNA, known as Hachimoji DNA. By tweaking and tailoring the structures of the regular bases, they made synthetic molecules that have the correct properties to be incorporated into the natural DNA structure. This DNA molecule would have the potential to store twice as much information as regular DNA and is thought to have possible applications within technology and data storage in the future.

Building on the existing DNA framework

Considering that the process of gene expression from DNA is the product of millions of years of evolutionary fine-tuning, it is unsurprising that scientists wanted to take the DNA model further and try to apply its template in new ways. It is, after all the most efficient way of storing and expressing vast quantities of information known to man.

The Hachimoji DNA is comprised of the four natural bases, as well as four more synthetically-made nucleotide bases, P, B, Z and S. These are each similar in shape to one of the natural bases, with slight variations in their bonding patterns. Within the four synthetic bases, S pairs with B and P pairs with Z. The research group created hundreds of Hachimoji double helixes with different combinations of the natural and synthetic base pairs to test whether they had to correct properties required to support life in the same way as ordinary DNA.

The characteristic property of DNA is its durability – no other genetic molecule is as stable or predictable. As a result of this, the four nitrogenous bases were always thought to be unique, but it turns out that the new synthetic DNA bases in Hachimoji DNA seem to behave in a similar way. The study has found that even after creating hundreds of Hachimoji molecules, the synthetic bases always bound to their complementary counterpart predictably. The researchers also managed to show that the double helices of the synthetic DNA remained stable no matter what order the bases were in. This is a crucial property of DNA which has allowed evolution and the survival of living organisms, as for this to happen helices must remain intact even if there is variation in the base sequence.

The final hurdle in this investigation was to prove that the synthetic, 8-letter DNA could not only store information, but that it could be read, transcribed and translated by enzymes into RNA. With this in mind, the researchers developed synthetic enzymes which actually successfully copied Hachimoji DNA into Hachimoji RNA! All of their results so far suggest that this synthetic hybrid molecule has the potential to act like the “real deal”.

It’s an exciting development in our understanding of evolution and the universe as a whole. It has been described as a conceptual breakthrough that natural DNA bases are not the only molecules that can form this stable and so-far unrivalled genetic material (DNA). According to Steven Benner, senior author of the research paper for this study, this strongly suggests that alternative structures like Hachimoji DNA could exist elsewhere in the universe, allowing for the evolution of life elsewhere – although it might look very different to life on Earth!

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Want to learn more? This article is based on:

Hachimoji DNA and RNA: A genetic system with eight building blocks
Four new DNA letters double life’s alphabet
Researchers Create Artificial DNA Bases
Storing data in DNA brings nature into the digital universe

by Annie Derry

As this year comes to a close, it feels right to reflect on the accomplishments that have been made by researchers at Newcastle University (with collaboration from other institutes) this year. The academic output of the University as a whole is, of course, extremely widespread, so I will be focusing on a small fraction of the research progress made in the Medical Sciences this year.

1. Fighting against drug-resistant Tuberculosis
Tuberculosis is usually treated by the antibiotic rifampicin; however, in recent years strains of Mycobacterium tuberculosis (TB-causing bacteria) have become resistant to it, making treatment very difficult and raising concerns over potential epidemics. Tuberculosis can be fatal without treatment and drug-resistant strains may become more prominent, leading to increased deaths worldwide. Newcastle University and Demuris Ltd researchers have made a promising discovery in a naturally occurring antibiotic called kanglemycin A. This antibiotic works in a similar way to rifampicin but has been identified to be active in working against Mycobacterium tuberculosis that are resistant to rifampicin. This is due to kanglemycin A’s ability to bind with stronger affinity to the RNA polymerase molecules of the resistant strain. This discovery can be used in drug development in the future in order to prevent any further fatalities from rifampicin-resistant tuberculosis.

Read the full article by Mosaei, Molodtsov, and colleagues

2. The first 3D-printed human cornea
The cornea is a fundamental part of the eye which acts as the outer-most lens, while preventing microbes, dirt and dust from entering. The cornea can become damaged due to injury, infection or conditions that cause corneal swelling, such as Fuchs’ endothelial dystrophy. There is often a shortage of corneas available for transplantation in people who need them, meaning that patients suffer visual impairment and potential blindness. These scientists at Newcastle University have devised a technique that uses stem cells from the corneas of healthy donors to create a “bio-ink”. This ink is then used in a 3D bio-printer to form the shape of a human cornea in under 6 minutes! The stem cells then use this as a template to grow into a cornea that can be used for transplantation. Although this method is a while away from being available to the general public it is an extremely exciting and influential development!

Read the full article by Isaacson, Swioklo, & Connon

3. A new link between Tuberculosis and Parkinson’s disease
This collaborative study led by Newcastle University, the Francis Crick Institute and GSK suggests that drugs we design for Parkinson’s disease might actually be able to treat tuberculosis as well. At the moment the focus for Parkinson’s treatment is to make drugs that block LRRK2, a protein which becomes overactive in the disease due to mutations in the LRRK2 gene. The results from this study indicate that this LRRK2 protein prevents the clearance of Mycobacterium tuberculosis by stopping phagosomes fusing with lysosomes in the immune response. Therefore, a drug that blocks LRRK2 protein could potentially be useful in helping the immune system to fight a tuberculosis infection.

Read the full article by Härtlova, Herbst, and colleagues

4. Further insights into reversing Type 2 diabetes
This study, funded by Diabetes UK, set out to decipher why some patients with Type 2 diabetes can recover to regular health through weight loss, and why other patients cannot. The study used data from a subset of individuals already taking part in the DiRECT (Diabetes Remission Clinical Trial) study which used non-surgical weight management to see whether it would lead remission of the disease. The researchers at Newcastle saw that there was one main difference between those who responded to the weight loss (and entered remission) and those who did not. The ‘responders’ had insulin-producing beta cells that appeared to start secreting the correct amount of insulin again after losing weight, while ‘non-responders’ had no change in insulin production despite weight loss. Responders were generally found to have lived with Type 2 diabetes for slightly less time on average than non-responders, which suggests that if beta cells are not under stress from increased fatty deposits for too long, they may still be able to recover when fat loss occurs.

Read the full article by Taylor, Al-Mrabeh, and colleagues.

5. Improvements in treatment for bone marrow cancer
Myeloma is a type of blood cancer that develops from plasma cells within the bone marrow. It has a 5-year survival rate of 50% and there is no complete cure, but there are ways to treat and manage the cancer in order to increase the amount of time patients survive for. In a study published by The Lancet Oncology, researchers at Newcastle and Leeds University monitored over 4000 patients in the UK for 7 years, in order to assess the efficacy of the drug lenalidomide (not yet available on the NHS). The patients had already completed their initial treatment and some were then randomly chosen to use lenalidomide during drug therapy. The results showed that lenalidomide significantly extended the lives of the patients and it reduced the risk of cancer progression or death by more than 50%. This study therefore shows a very promising new treatment method for people living with myeloma, which hopefully will be seen within the NHS before too long.

Read the full article by Jackson, Davies and colleagues

These publications are representative of just a tiny amount of the work at Newcastle University that has had global success this year, and some additional links are listed below. Look out for more North East research developments in 2019 – happy New Year!

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If you would like to learn more about life science research news from Newcastle University please follow the links: https://www.ncl.ac.uk/medicalsciences/news/ & https://www.ncl.ac.uk/press/archive/

Breakthrough in childhood brain cancer 
Tobias Goschzik PhD, Edward C Schwalbe PhD, Debbie Hicks PhD, Amanda Smith MSc, Anja zur Muehlen, Prof Dominique Figarella-Branger MD et al.

Potential to use gene-editing to halt kidney disease 
Simon A. Ramsbottom, Elisa Molinari, Shalabh Srivastava, Flora Silberman, Charline Henry, Sumaya Alkanderi, Laura A. Devlin, Kathryn White, David H. Steel, Sophie Saunier, Colin G. Miles, and John A. Sayer

A breast cancer drug that could be used to treat leukaemia 
Natalia Martinez-Soria, Lynsey McKenzie, Julia Draper, Georges Lacaud, Constanze Bonifer, Olaf Heidenreich et al.

Stalling the cell cycle to put cancer cells to sleep 
Teemu P. Miettinen, Julien Peltier, Anetta Härtlova, Marek Gierliński, Valerie M. Jansen, Matthias Trost and Mikael Björklund.

by Annie Derry

The idea of tailoring treatment to best fit a patient’s needs has been around for as long as medicine itself. Each individual is different, and bedside manner is, of course, tailored according to a patient’s personal circumstances. Medicinally, we can currently alter treatment to try and ensure that medications are right for a patient, considering their medical history and potential side effects.

As we have come to know more about pharmacology, disease, and their links to the genome, more specific and even individualistic medical treatment has become more of a real possibility. The idea of personalising medicine is to move away from the blanket approach currently used for a lot of disease treatments, and to delve further into the details about each patient’s genetic make-up in order to see their risk of developing certain diseases and what their potential responses to therapeutic methods may be. Studying a patient’s unique genome could prove vital in providing the best possible treatment, in the safest way, as well as giving the potential for earlier diagnosis and risk assessment. It promises to, overall, improve healthcare for patients while keeping costs relatively low.

What changes how we respond to drugs?

Many factors affect how we respond to anything that we consume or put in to our body. Our physical properties such as, height, weight, age and gender can all affect how we assimilate and metabolise drugs. These fundamentals are already considered in pharmacokinetics and pharmacodynamics when calculating dosage. It is now understood that there are also certain proteins that can affect drug metabolism, and scientists can now up to a point, predict, how a patient might respond to a drug based on the expression of these proteins from their genes. There are now technologies known as HTS (high throughput sequencing) techniques available that allow millions of DNA fragments to be sequenced simultaneously. The rise in genomic technology has seen the length of time taken to sequence a whole genome decrease from 13 years (the first ever human genome sequenced) to a matter of 1 or 2 days. Most of the time it is only the exome (expressed part of the genome – the exons) that are sequenced for medical purposes, due to time and cost restrictions. However, sequencing whole genomes also allows scientists to develop an understanding of the unexpressed, or ‘nonsense’ DNA regions.

How is personalised medicine currently used?

All over the world preventative measures can be taken by those who wish to have their genome privately sequenced and analysed, for around £1000. This involves a whole exome sequencing and includes estimations of your genetic disposition towards various diseases such as cancer and some rare genetic forms of Alzheimer’s disease amongst others; although, most diseases are still heavily impacted by environmental factors. In the NHS, similar genetic analysis is now commonplace. In her 2017 annual report the Chief Medical Officer for England, Dame Sally Davies, stressed her excitement for the genomic revolution and her ambitions for genetic testing to be as routine as blood testing patients in the next 5 years. This already occurs for those who are deemed at higher risk of having a genetic disposition for a disease, e.g. testing people for variants within the BRCA1 and BRCA2 genes to determine any higher risk of breast/ovarian cancer. This allows people to assess their risk and take any precautions necessary to prevent the cancer/to reduce its effect in their life.

Potential problems?

The benefits of personalised medicine seem varied and undeniable. However, there are some cases where genome analysis could be taken out of context and used in the wrong way. An extreme example of the potential capabilities of genomic analysis is that of the Chongqing Children’s Palace, a summer school in China, which provides a genome sequencing service for parents who want to know their child’s ‘capabilities’. It is claimed that they can use the children’s genome sequence to determine their best qualities, including what jobs they would be best at, and what activities they should be participating in. The ethical issues with this speak for themselves, and without taking the results with a pinch of salt and an understanding that these factors cannot be accurately determined just by genome analysis, there is potential for a big problem.

In the U.K. there are also some concerns about the use of patient data, and whether information gathered about patients from genetic testing could get in to the hands of organisations other than the NHS. There are worries that this could result in changes to people’s ability to get life insurance, mortgages and other forms of loans. It is reasonable to assume that for people deemed at high risk of developing life-threatening disease, these things could be heavily affected if their genome data is not protected.

Overall, the pathway we are on to a more personalised medical experience is an exciting and quickly moving one. It is important to remember: we are fundamentally defined by our genetic make-up, but most diseases are also profoundly impacted by our surrounding environment. We cannot currently wholly and accurately define all disease risk using genome analysis, but it can certainly help our understanding of personalised medical treatment for each unique patient. Genetic testing and sequencing will almost certainly become a routine part of our lives, hopefully for the better!

Want to learn more? This blog post was based on:
Lone Frank – My Beautiful Genome Personalised Medicine 
Personalised medicine in the UK
Sequencing your genome, what does it mean?

by Annie Derry

Nobody wants to get older, but ageing is a fact of life. Nearly everyone tries to combat its effects, whether it’s by eating superfoods or buying anti-wrinkle cream. However, there are some age-related diseases that seem to be unavoidable due to our lifestyle or our genes.

As life expectancy increases due to better healthcare, so does the proportion of older people (usually medically defined as those over 65 years old) within the population. Studies about how older people are viewed and attitudes towards ageing have never been more relevant, and some studies have found that a positive attitude towards ageing can have substantial impact on health and life expectancy.

Normal healthy ageing, or ageing processes that occur without the interruption of disease, are an inevitable part of life. These are the processes that cause greying hair, weakened joints and gradual cognitive decline amongst other things. We are still learning about ageing. It was thought until relatively recently that the neurons in our brain die as we grow older; however, it has become apparent that, without the presence of pathologies like Alzheimer’s disease, our brain cells remain almost totally intact until we die. This suggests that our cognitive capabilities should also remain, and studies have shown that we tend to assume our brain function is worse than it really is as we age.

Ageing stereotypes – fact or fiction?

It is understandable that as we grow to know more about ageing processes and diseases that we tend to focus more on the negatives. Studies such as the Longitudinal Ageing Study have been working to address these perceptions. The study suggests that, in general, members of the public tend to believe that older people are unhappier, lonelier and have fewer social interactions than they do in reality.

It seems that the stigmas associated with old age leave us with a skewed impression of how older people feel about their life situation. It has actually been found that older people are more satisfied, fulfilled, emotionally stable and more able to handle complex situations than younger counterparts!

Attitude vs outcome

It is quite well accepted that a good attitude towards life in general is thought to have a positive impact on a person’s health and well-being. It seems that this becomes of particular importance as a person grows older. This is mainly due to the fact that people who think and act like they are younger than their age are more likely to be physically active and engage in more social situations than a person who views themselves as “too old”.

An example of how such attitudes can affect health is when men experience premature baldness. Baldness is a trait associated with ageing, and in a study conducted by Ellen Langer, a Harvard professor, it was found that men experiencing premature baldness had a higher incidence of age-related health problems than men without this issue. This suggests that these men might feel older than they really are, and that the feeling of premature ageing could lead to more age-related issues. Langer also found that people whose partners are significantly older than themselves tend to experience age-related health problems at a younger age. The same study suggests the opposite is true for people with younger spouses. This indicates that a younger lifestyle may help to combat the effects of ageing for longer.

There is still so much to explore in relation to healthy ageing and combatting cognitive and physical decline. Unfortunately, some of us will always be susceptible to age-related disease according to our genes and the influence of our environment. A positive attitude towards ageing cannot stop the process. However, there is definite evidence to suggest that positive thinking towards our impending older years have the potential to increase our quality of life. Positivity can act as a self-fulfilling prophecy to help us to be happier and healthier for longer.

Interested in learning more? This blog post was based on:

André Aleman – Our Ageing Brain
The Longitudinal Aging Study Amsterdam
“Good news about the ageing brain”

by Annie Derry

Since the dawn of genetics, it has been well established that characteristics are passed from parent to offspring through DNA sequences. It was thought until recently that there were rigid rules to which inheritance abided: that traits could only be passed onto offspring if they, themselves, were caused by changes to the amino acid sequence making up DNA.

This was a perfectly rational conclusion based on what we observe in nature, as phenotypes we acquire over our lifetime due to our environment do not usually affect our DNA. How would these be passed on? It seemed sort of impossible.

Enter: Epigenetics.

What had not been realised until (relatively) recently is that the DNA sequence can be altered in more ways than a change to the underlying amino acid (and nucleotide base) sequence.

Epigenetic changes are chemical alterations to the genome that result in the switching ‘on’ or ‘off’ of genes. These chemical modifications can include DNA methylation of certain areas, as well as histone modification. They essentially change how easy or hard it is for that region of DNA to be unravelled, transcribed and translated into a protein (in other words, expressed). Many factors have been found that could potentially cause epigenetic changes in the body, such as stress, physical activity and diet, and it is now thought that these changes can be inherited.

Wiping the slate clean?

It was previously thought that chemical changes to the genome were accumulated over an individual’s lifetime, but that they would be removed in the process of reproduction. It is now believed that this is not the case, as changes to the epigenome seem to be able to jump the generational barrier.

A widely used example of transgenerational epigenetics is the study of the Dutch Hunger Winter (1944-45), a terrible period of starvation for the people of The Netherlands. Based on well-kept medical records, pregnant women and their offspring were studied to understand the health impact of the unique conditions they were subjected to.

The interesting observation was that differences in the timing of malnutrition during pregnancy went on to affect not only the children’s weight at birth, but their health in adulthood too. Some babies (those only affected by malnutrition in early pregnancy) went on to have above-average weight in adulthood, and even to be more prone to obesity and cardiovascular disease. Those born underweight due to malnutrition in later pregnancy remained smaller in adulthood, with lower than average obesity rates. Records even suggested that the grandchildren of those malnourished women were affected similarly. A follow up study indicated that the children – many decades after initial malnutrition in the womb – had less DNA methylation of the IGF2 (insulin-like growth factor) gene than their unaffected siblings. This gene codes for an important protein in growth, thus the results suggest that an epigenetic change had taken place and could have contributed to the growth patterns of those affected children.

This gives us a small insight into how one environmental condition might cause a chemical imprint on the epigenome of a foetus that remains for their entire life and is passed on to their children.

What does this mean for us?

This does not mean to say it is certain that every little thing we do results in a genetic imprint that we pass on to our children and subsequent generations. We don’t know yet whether smoking or eating 5 fruits and vegetables everyday will be detrimental to the health of our unborn children. However, it is now clear that some aspects of our lifestyle will cause an imprint on our genome, and that imprint might not be wiped clean when we reproduce. All this means is that we can decide to take more care of ourselves, knowing that our actions may not only affect our own bodies, but those of our offspring. That being said, the field of epigenetics is a relatively new one and there is much, much more to be understood about modes of inheritance.

Interested in learning more? This blog post was based on:
Nessa Carey – The Epigenetics Revolution
Tim Spector – Identically Different
Epigenetic inheritance and the missing heritability
Transgenerational Epigenetic Inheritance: myths and mechanisms