Author: Joanna Ciafone

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Annie Derry

New year, new research: Some of the cutting-edge Life Science research that came out of Newcastle University in 2018

by Annie Derry

image source: https://pixabay.com/en/lab-science-scientific-chemistry-512503/

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

image source: https://pixabay.com/en/human-eye-iris-macro-view-cornea-995168/

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.

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Leonie Schittenhelm

From cinnamon sniffers & milking maids – the holiday season in the lab

by Leonie Schittenhelm

Ah, it’s that wonderful time of the year. Christmas songs on every radio station, the socially acceptable amount of cookies you’re allowed to eat reaches new highs and despite gift madness, it’s nice to look forward to spending some time with those nearest and dearest to us. But scientists wouldn’t be scientists if they couldn’t make even the jolliest of all times relevant to their research. With no further ado, a special Christmas collection of published papers you can bring up over Christmas lunch with your grandma when she asks you what it exactly is that you’re doing – you’re welcome.

freely available on https://pixabay.com/en/cinnamon-aroma-spices-condiments-1971496/

Take a sniff – the smell of nutmeg, clove and – is that cinnamon? – wafts through the house and you just know it’s Christmas. Researchers actually found out that not only do people associate the smell of cinnamon with Christmas, they also tend to enjoy smelling it a lot more when the cold season comes around. I mean, who wants a gingerbread latte in late July, right?

image freely available https://pixabay.com/en/cow-beef-snout-hoofed-animals-3383624/

“On the 12th day of Christmas my true love gave to me –“ – we’ve probably all head this song and despite frequent difficulties in remembering the correct order it is a well-loved classic Christmas carol. But Diane M. Dean took a rather unsentimental but even more humorous look when she published her paper ‘Cost analysis: the acquisition of the items listed in a popular song’ in 2007, where she meticulously estimates the total price for the gifts mentioned in the carol. An example here: To give your true love 8 maids a-milking you need 8 milk maids paid at current minimum wage, 8 cows of course and also 8 buckets (a bargain at $5/bucket) and 8 milking stools, coming to the whopping cost of $2,166.56 for only one of the items on your beloved’s Christmas wish list. While she notices a slight increase in cost between the 2005 and 2006, she also advises: “All errors and omissions will be cheerfully admitted to. This study should not be taken seriously. If you find yourself tempted to quote this study as a definitive authority at your next Christmas Party, please administer yourself more alcohol.”.

image freely available https://pixabay.com/en/celebration-christmas-cuisine-315079/

Let’s be real – most days around Christmas will be spent in some sort of food coma. In the paper ‘The Christmas Feast’, scientists measured weight and blood glucose levels before and after Christmas and found that all 35 study participants gained weight over the holiday period, with scientists estimating that an excess of around 6000 calories were ingested. But fear not, rather than admonishing people for indulging over the days around Christmas, the researchers realistically stated ‘This study is not likely to affect any future Christmas.’. Phew, glad we got away with this one…

image freely available https://pixabay.com/en/christmas-xmas-table-setting-love-791110/

And to end this article on a more whimsical note, research published in the Journal of Happiness Studies, titled ‘What makes for a merry Christmas?’ actually found what we suspected all along: rather than chasing expensive gifts or being stressed about drying out the Turkey, people are happiest on Christmas if they spend quality time with their loved ones. So wherever you are this festive period, I hope you are surrounded by people you love when you tuck into that Tofurkey – environmentally friendly consumption being another predictor for a cheerful holiday season.

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William Gan

The marvels of Life

by William Gan

As part of my undergraduate course, I’ve just recently been given the opportunity to visit the Life Science Centre, a prize-winning educational facility cum tourist attraction located in Times Square, Newcastle. The Life Science Centre is part of the Centre of Life, one of the projects funded by the Millennium Commission as a registered charitable trust. It is an internationally acclaimed self-funding ‘science village’ that also houses research laboratories, biotechnology companies, and National Health Service (NHS) clinics.

Centre for Life logo: If you look closely, the F actually resembles a duplicated chromosome!

Walking into the centre, it felt as if I was entering a large indoor theme park as the vibrant colours that decorate the exhibits come into full view. Fortunately, visitors are strongly encouraged to unleash their child-like instincts to wander and explore the various sections. Hence, it’s a well-known hotspot for schools to organise trips for young students to expose them to the world of science!

One of the permanent exhibitions, the Curiosity Zone, presents a range of interesting sections that includes spinning turntables, interactive walls and air-suspended beach balls, encouraging visitors to experiment through trial and error and have fun despite the absence of scientific content. It also features a ‘making space’ where younger ones can be armed with glue guns and cardboard amongst other materials to exercise their imagination and to get some hands-on action.

Noel Jackson, Head of Education at Centre for Life, says: “We want to break the stereotype that science isn’t all head knowledge, but more of the entire learning process that one experiences in discovering something.”

In the Experiment Zone, participants will be able to take part in actual experiments using real chemicals under supervision while donning lab coats. By creating opportunities for families to experience scientific discovery together, parents can foster the sense of scientific involvement in their children. The Brain Zone on the other hand explores how different disciplines can come together to study the mind. Optical illusions and other interactive tools are joined alongside relevant scientific content in presenting the inner workings of the mind.


Experiment Zone: Well-equipped lab stations with instructive digital panels for the budding scientist!

The Science Theatre is where the audience can experience the ‘artsy’ side of science, it’s without a doubt my most favourite section in the centre. Set in a dome-shaped enclosure with a dimly lit stage and rows of cushioned red seats, Science Explainers will tell a story while exploring a scientific topic with the use of live interactions and demonstrations. Shows are filled with visual wow factors ranging from gorgeous chemistry to fiery bubbles that may seem like pure magic. I personally feel that this concept is a great way to present science in an entertaining way especially towards a younger generation.


“By blurring the boundaries between science and arts, we hope that our audience can learn to watch closely, be curious and to ask questions, and at the same time see the beauty in science,” says Elin Roberts, Head of Public Engagement at Life Science Centre.

In the planetarium, visitors can experience an immersive, virtual tour of the night sky as well as view the solar system in high definition. While the audience are seated in comfy chairs, the planetarium presenters will describe exciting space endeavours while journeying through the cosmos! Speaking of space, special events are also available for adults or ‘big kids’ with the most upcoming one including discussions on the myth of a cheesy moon and lunar space missions, accompanied by a cheese and wine tasting session.

Mr Jackson further explains: “Parents in general play a key role in shaping their child’s perspectives on life, finding joy and genuine enthusiasm in a field like science can influence the younger generation to also find their own passion in life.”

Want to learn more? Check out Newcastle’s Centre for Life on their website, or visit them in person soon!

 

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Cassie Bakshani

Say ‘no’ and work better

by Cassie Bakshani

As early-career researchers, and as young people in general, the pressure to say ‘yes’ can become a little overwhelming. ‘Yes’ to work requests, ‘yes’ to exciting collaborations, ‘yes’ to having at least some semblance of a social life.

Whilst no doubt there are plenty of useful opportunities that can enrich your life and career, it’s important to recognise that an opportunity, even one that is perceived to be life-changing and unmissable, is only actually life-changing and unmissable if you have the capacity to fully commit yourself to it. If you aren’t able to input sufficient time and resources, the experience won’t be productive for you, or anyone else involved. Really, what I’m trying to say, is there is also great value in politely declining, or in other words, saying ‘no’.

Saying no, contrary to the voice in your head, does not represent failure or inadequacy. It’s about knowing your worth and the extent of your capabilities, whilst acknowledging that by taking on anything further, you could jeopardise the success of existing commitments. Spreading yourself too thinly can have serious implications, not only for your professional integrity, but more importantly, for your mental and physical wellbeing.

Practise and embrace saying no. Some of the most accomplished scientists in history are renowned for their dedication to pondering specific problems, not on the length of their ‘to-do’ list. Slow the pace, reduce the complexity and fulfil the obligations you already have, to the very best of your ability. In doing so, you’ll give yourself more time to appreciate the quiet moments of contemplation.

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Annie Derry

Welcome to the era of Personalised Medicine

by Annie Derry

Image source: https://pixabay.com/en/health-medicine-tablets-pills-846863/

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?

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Joseph Smith

Are current cancer models limiting effective drug discovery?

by Joseph Smith

image freely available from https://pixabay.com/en/laboratory-analysis-chemistry-2815641/

Cancer is defined as an uncontrolled division of abnormal cells, resulting in a malignant growth or tumour. Recent reports suggest that approximately half of us will be diagnosed with the disease in our lifetime. Moreover, it is predicted that cancer incidence rates will increase by 68% from 2012 to 2030 worldwide. Fortunately, our understanding of how cancer occurs and progresses is also increasing, ] providing opportunities to identify novel druggable, targets. Our improved understanding has also revealed unforeseen challenges that complicate the journey of new drugs from bench to bedside. This is evidenced by the fact that a staggering 95% of leading drug candidates do not make it to the clinic. But why? One of the main reasons is our inability to accurately replicate cancers as they occur in humans. Researchers currently employ a wide array of cancer models in order to understand the biological processes that drive cancer and to test potential therapies. In this article I will discuss some of the most commonly used cancer models and how they might be limiting effective drug discovery.

Cell lines

The first, and probably most well-known, cell line was established in 1951 and derived from a cervical adenocarcinoma tissue biopsy. Henrietta Lacks, the patient from whom the biopsy was taken, succumbed to her cancer only months later however HeLa cells are still used in cancer research to this day. HeLa cells, like other immortalised cell lines, have the ability to grow and divide indefinitely. Furthermore, researchers can easily manipulate cell lines, for example, by increasing or decreasing the amount of a certain protein we may better understand its function within the cell. These traits have resulted in their routine use and they are an essential tool for cancer research, allowing scientists to elucidate the molecular biology of cancer cells. However, cell lines represent a massively simplified version of human cancers, lacking heterogeneity or a tumour microenvironment, including an immune system. These differences mean that a drug that is effective in vitro will not necessarily perform as well when applied in vivo.

Mouse models

In order to better recapitulate human cancers scientists will often utilise mouse tumour models, establishing cell line-derived xenografts within immunocompromised mice. After the cancer cells have been implanted researchers may then treat the mice with a novel anticancer drug, with the view of slowing or ideally preventing cancer growth. Mouse models allow for evaluation of new therapies in vivo within an environment more similar to that seen in humans. For example, the cancer cells have the ability to interact with the microenvironment in which they’re placed. However, in using cell line-derived xenografts these tumours still lack the inter-tumoral heterogeneity seen in the clinic. Notably, this heterogeneity is likely one of the reasons for low response rates seen in many clinical trials, as small populations of drug-resistant cancer cells can ultimately repopulate patients’ cancers.

What are the alternatives?

Both cell lines and mouse models are useful cancer models, but both have major limitations and do not capture the complexity of human cancer. As a result, novel anticancer drugs that prove to be effective in these models often do not have the same effects in humans. So how do we solve this problem? With advances in technology, scientists have developed a multitude of models that aim to overcome the aforementioned issues, such as patient-derived xenografts and explant culture. I will discuss these methods in more detail in the next issue of {react} magazine!


Issue 12 of {react} magazine is currently under development by our dedicated team of student writers, editors and designers. Keep an eye on this blog, our twitter, and facebook for information on the release date!

 

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Leonie Schittenhelm

How to make a baby with three parents

by Leonie Schittenhelm

Picture freely available from https://pixabay.com/en/mom-daughter-son-relationship-2208928/

It was only about 18 months ago that the Human Fertilisation and Embryology Authority (HFEA) granted the UK’s first licence for Mitochondrial Replacement Therapy (MRT) to the Newcastle Fertility centre. But why would you need to replace mitochondria and what does that have to do with making a baby?

Mitochondria, often cheekily referred to as ‘the powerhouses of the cell’, are enormously important to transform the things we eat into the energy carrier ATP our cells use to drive basically all their activities. It is no surprise then that mitochondrial diseases, a collection of rare conditions that affect these vital cell organelles, can have far-reaching effects on the people who have them. Depending on where the dysfunctional mitochondria are located, symptoms can include epileptic seizures, muscle weakness, dementia and disease in multiple vital organs. Indeed the brain, nerves and muscles show the most severe symptoms as they use the most energy. While 0.5% of people could be classed as having a mitochondrial disease, only about 0.2% show severe symptoms, as a significant proportion of a cell’s energy suppliers has to be affected to cause disease. While these conditions can be caused by infection or adverse reactions to medication, they can also be passed down from your mother.

Here is where an interesting thing about mitochondria comes into play: you only inherit them from your mother. While fertilisation of your mother’s egg with your father’s sperm should shuffle their genes to make up a new person, this isn’t quite the same for the mitochondria present in the egg, which has its own separate DNA that the sperm cell does not contribute to at all. Here is where mitochondrial replacement therapy comes in. Mothers who are at risk of passing on debilitating and often life-threatening mitochondrial diseases to their children can now, with help of in-vitro fertilisation, transfer the nucleus of their own egg cell merged with the sperm cell of the father, containing all their combined genetic information, into an egg donated by a donor with healthy mitochondria. This not only allows these parents to have healthy biological children, but it also restricts the disease from being transferred to the next generation.

But what has happened in the 18 months since the HFEA has granted the licence to perform Mitochondrial Replacement Therapy? In February it was announced that two women affected by a mitochondrial condition called MERRF were chosen to be the first ones to receive the revolutionary therapy in the UK. While they are not the first to receive the treatment, they benefit from an integrated care pathway that includes rigorous testing of the health of both mother and child throughout pregnancy and into the first years of life, ensuring that any risks associated with the method are mediated. This could mean a huge improvement to the quality of life of the up to 150 children that have a risk of being born with mitochondrial diseases in the UK each year and hope for the carriers of mitochondrial disease that often have to think carefully if having their own children is even a possibility. And who knows, maybe we could even welcome the first British “3-person” baby before the end of this year.

If you want to read more about mitochondrial replacement therapy: Gorman, Gráinne S., Robert McFarland, Jane Stewart, Catherine Feeney, and Doug M. Turnbull. “Mitochondrial donation: from test tube to clinic.” The Lancet 392, no. 10154 (2018): 1191-1192.

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Cassie Bakshani

Virtual reality: the new kid on the block in memory research

by Cassie Bakshani

Memories are intrinsically linked to context; sounds, smells and other types of sensory stimuli can affect how a memory forms and is retrieved. The environments associated with conventional neuropsychological assessments, such as inside an MRI scanner, is a very different context than that of everyday memory situations. Consequently, traditional methods often do not accurately reflect an individual’s regular day-to-day memory ability.

Image freely available on pixabay.com

In light of this, virtual reality (VR) technology is currently being explored as a tool to aid memory research. VR is defined as any three-dimensional, computer generated environment that transports the user to a place that is different to that of their physical surroundings. Within this space, the user can explore, interact with objects, or perform certain actions. Virtual reality alleviates the issue of context associated with conventional memory tasks, as it provides a unique platform, whereby an immersive visuospatial context can be generated. Within the virtual environment, memories can be formed and/or retrieved in relation to a higher degree of prosaic cognitive demands, thus enhancing the ecological relevance of the data collected.

Data from VR headsets can be downloaded and analysed wirelessly. By recording the brain signals of a participant whilst they are simultaneously immersed in the virtual environment, specific neural oscillations can be identified that are associated with learning and navigating through new environments. Researchers are then able to quantify how these oscillations relate to successful memory formation. VR technology is revolutionising memory research by allowing us to understand more clearly what is happening in the hippocampus and other parts of the brain during the formation of new memories and the retrieval of old memories.

From a methodological perspective VR is advantageous as it allows researchers to standardise assessment conditions and to maintain experimental control over critical features of the learning and testing experience. Another benefit is that environments can be constructed that would be impossible, or at least highly impractical, to create using traditional methods. For example, it is possible to rapidly modify environmental features and, in doing so, customise the visuospatial context to meet specific task requirements- participants can even be teleported between environments and thus, contexts. Virtual environments and scenarios explored in the literature for memory research purposes include a car, a shop, a kitchen and a maze, amongst others. This ability to generate and manipulate the environments more commonly found in daily life is significant because it ensures the results are more representative of everyday memory situations.

The applications of VR in memory research are extensive and its worth has already been realised in many areas. Applications include rehabilitation following post-traumatic amnesia, treatment of individuals with amnestic mild cognitive impairment, understanding prospective memory in stroke patients and the early detection of Alzheimer’s disease. One particularly concerning aspect of Alzheimer’s disease, and other types of dementia, is the loss of sociality and subsequent feelings of isolation, which often succeed the loss of physical autonomy. VR is now being implemented as a form of therapy, called reminiscence therapy, to help combat this issue in individuals with dementia. With the help of family members and carers, the person can be immersed in familiar environments or those that relate to important parts of their past. The hope is that this technology will encourage the generation of autobiographical memories and help those with dementia to retain or regain a sense of self, and along with it a renewed confidence to socialise.

It is truly remarkable to think that technology that started out as a means to provide interactive theatrical experiences could have such far-reaching implications. Not only in how we study brain functioning and cognition in humans, but also how we respond to and treat those with serious cognitive impairments.

Want to learn more? This article was based on:
https://www.frontiersin.org/articles/10.3389/fnins.2018.00408/full https://www.ncbi.nlm.nih.gov/pubmed/22261400 https://www.sciencedirect.com/science/article/pii/S0165027018300815?via%3Dihub http://newsroom.ucla.edu/stories/neuroscientist-harnesses-the-power-of-virtual-reality-to-unlock-the-mysteries-of-memory

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Liza Olkhova

Microbes and mood: the gut-brain axis

by Liza Olkhova

One of the first concepts stating that fermented foods might be beneficial to our health was proposed by a Russian scientist, Ilya Mechnikov, who discovered the endocytosis and pinocytosis functions of macrophages, where these immune cells engulf pathogens. He boldly claimed that consumption of fermented food may increase lifespan in his book titled The Prolongation of Life: Optimistic Studies.

We hear a lot on the news about the roles of prebiotics and probiotics in human health. Along with the rest of commensal microbiota, these bacterial species are well-understood to help with our digestion and shape our immunity. But can gut bacteria also influence our central nervous system function? In recent years, a boom in microbiome research provided us with new exciting insights into how trillions and trillions of microbes thriving inside the human organism may modulate its host’s health.

One of the first and very important studies that looked at the interplay between the microbes and their role in modulating stress hormones (released from adrenal glands when we get ill or stressed) was by Sudo and colleagues in 2004. They have shown that mice that were completely germfree released more of the stress hormone corticosterone (called ‘cortisol’ in humans) than their non-germfree counterparts (so-called ‘specific pathogen-free’). Interestingly, when germfree mice were given Bifidobacterium infantis, their stress hormone levels became less pronounced.

This study has ignited a chain reaction of many more animal studies that included behavioural work and human studies. Probiotic consumption was linked to improved mood, decreased depressive and anxiety scores in humans. The specific microbiome cluster (determined by the abundance of a particular type of bacteria in your GI tract) may not only dictate your emotional responses to what you perceive, but also predict your brain’s structural features as shown in a functional MRI study!

There has also been a clinical trial conducted by Akkasheh and others in patients with major depressive disorder that split patients into two groups: one was taking probiotic-containing pills and the other one was taking placebo. Patients and researchers were blinded to patients’ group allocation to prevent any bias influencing the results. It was discovered that patients supplemented with probiotics for 2 months had greater improvements in their symptoms compared with patients receiving placebo. What’s more, their C-reactive protein levels were also decreased, meaning they had decreased inflammation levels.

Microbiota can also produce or consume the major neurotransmitters – messengers of our brain, such as serotonin and dopamine. Clearly, there are a lot of unanswered questions about the microbiome and its links to major diseases, such as neurological disorders (for example, multiple sclerosis) and a lot more research is needed to show a more defined picture of the gut-brain axis.

Was Mechnikov right in his predictions made over a century ago and could a probiotic a day keep the doctor away?

Interested in learning more? Here are some useful links: https://www.ncbi.nlm.nih.gov/pubmed/15133062 https://www.ncbi.nlm.nih.gov/pubmed/28661940 https://doi.org/10.1016/j.brainres.2018.03.015 https://www.ncbi.nlm.nih.gov/pubmed/26706022

Image source: https://www.optibacprobiotics.co.uk/learning-lab/blog/gut-brain-axis
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Emma Kampouraki

Pharmacogenetics; from conception to implementation

by Emma Kampouraki

While a vast proportion of our knowledge about drugs focuses on the mechanism of action, the indications and the adverse events that may appear, we are still at an early stage to understand fully the interaction between drugs and our genetic background. It is well established that such interaction is present and has a great impact on the response of patients to a number of commonly used prescription medication.

The pharmacogenetic approach in drug prescription (Source: J Clin Invest. 2007;117(5):1226-1229)

After the observation of substantial differences between patients’ responses, while receiving the same treatment, it became apparent that the “one size fits all” design is not effective anymore. Vogel in 1959, described the term ‘pharmacogenetics’ as the field that studies the way in which one single change in a gene influences the response to a drug. However, after the completion of the Human Genome project in 2003, the term ‘pharmacogenomics’ was used to describe the influence of the whole genome to the drug response. Pharmacogenetics is a subspecialty of Pharmacogenomics and does not require whole genome sequencing, whereby analysis of all the genes is performed. The two terms are often used interchangeably, but this sometimes can cause confusion.

The importance of pharmacogenetics is also reflected in the recent clinical trials. There is an increasing interest to study how drug responses are affected by patients’ genetic variations as demonstrated by the 1060 studies about pharmacogenetics or pharmacogenomics to date.

There are numerous examples of drugs that are influenced by certain genes, either regarding their pharmacodynamics or pharmacokinetics. One important gene that encodes a microsomal liver enzyme from the P450 complex is CYP2D6. As shown in 1970, this gene affects the elimination of debrisoquine, an antihypertensive drug. People carrying certain alleles (i.e. versions) of this gene have altered elimination rates and therefore different duration of action.

Also, certain alleles of the NAT2 gene lead to the production of less N-acetyltransferase which causes slower acetylation and elimination in patients and side effects from the longer stay of the drug in the blood circulation.

Similarly, suxamethonium, a general anaesthetic, can cause prolonged apnoea in patients with defects in BCHE gene producing low activity of the enzyme that normally breaks down suxamethonium. Primaquine, a drug against malaria, has been shown to cause acute haemolysis in patients with G6PD enzyme deficiency.

The most important example is that of warfarin. This anticoagulant drug has a very narrow therapeutic window, causing serious, potentially lethal side effects after small instabilities in its levels. The dose for each patient has been proven to be dependent on two genes, CYP2C9 that affects the elimination by metabolising the S- enantiomer of warfarin and VKORC1, the actual target enzyme that warfarin inhibits.

In fact, FDA updated the drug labelling in 2007, recommending very specific dose adjustments after genetic testing of these two genes in combination.

In order to organise the information from the studies, a database was created, called PharmaGKB, which can easily facilitate the acquisition of information among researchers and clinicians and the actual clinical implementation of pharmacogenetics.

So, what exactly are the benefits from translating pharmacogenetic information into clinical practice? In a study of 2008, it was estimated that over one fourth of commonly prescribed drugs have some type of genetic information that could be used in medicine. It is possible to predict interactions between drugs, potential side-effects and individualization of treatment, such as informed choice of drugs or dosage as in the case of warfarin.

Currently, several kits for pharmacogenetic testing for warfarin are commercially available with their cost continuously decreasing, making genetic testing easier than ever before. In Freeman Hospital, Newcastle upon Tyne, such a kit utilises literally a droplet of patient blood and provides the genetic analysis result within 40 minutes after a fully automated run.

A more personalized design of new drugs, especially in population level, can be achieved using the different allele frequencies in genes that are important for drug activity and metabolism. This way, each population would receive more appropriate drugs schemes for its most prevalent genetic changes. Although there is a great number of challenges in this field, including ethics and concern about potential access to the data, which can be partially addressed by the advances of technology, the benefits are many and the cost-effectiveness of the implementation of pharmacogenetics is reported in many studies. The field of pharmacogenetics has therefore a lot to offer to the scientific and medical community.