This week’s featured PhD…

This week’s featured PhD…

Jack Barton, PhD Student
University of Manchester

Jack

I am a PhD student at the University of Manchester who likes to study, talk, and occasionally even take time to, sleep. Before you ask, despite having given a talk on the subject, no, I cannot interpret your dreams. So, I’ll have no mention of giant chickens giving you a surprise test while only in your underwear. You have been warned.

Sleep loss, unusual experiences, and eager students

What’s the longest you have gone without sleep? Maybe you’ve gone a day or two? I’m sure it has probably been long enough to notice the extreme tiredness which follows and a few other weird experiences. The longest I have gone without any consolidated period of sleep was during my freshers’ week at university.  I was enjoying myself free from adult supervision and during this time I probably averaged about an hour or two sleep a night. I only realised how exhausted I was when one day in my room, preparing for another night out, I closed my eyes and the floor in front of me suddenly burst to life. A crowd of people emerged from the ether chatting to one another, dancing, and generally having a good time. None of them payed any attention to me but I could hear a mass of indistinguishable voices. Upon opening my eyes this phantasmagorical party vanished. I closed my eyes again and they waltzed their way back into my room. Unless someone was playing an extremely elaborate prank on me, I was clearly hallucinating scenes from the past few days. As a psychology student, I found this weird but more importantly, incredibly interesting. It has been several years since that experience but upon starting a PhD in sleep I have hunted down, systematically, research to back-up the ghostly party I witnessed during my first foray in university life.

Studies conducted in the 1950s and 1960s collaborated my own experiences. In 1962, a small group of healthy medical students were deprived of sleep for 4 days and what they saw, heard, and felt were recorded during the study. You can read about their experiences in detail here (http://bjp.rcpsych.org/content/108/455/457). To begin with, the students experienced complex visual hallucinations whereby they saw an angry elderly woman. After she finished staring at them she would creepily disappear face last in homage to the Cheshire Cat from Alice in Wonderland. As time went on, these sleepy students also experienced hallucinatory distortions of surfaces, and persecutory delusions whereby one participant felt they were being drugged by the experimenters to make sure they produced interesting results. This particular student found clues in everything to confirm this delusion despite there being (I hope) no basis for their belief.

Alongside scientific studies, there have been attempts to try to set world records for sleep loss including such able contenders as a spate of radio DJs in the late 50s and early 60s keen to kickstart their careers (https://www.youtube.com/watch?v=4MT8ekBGyM4). The most famous attempt at setting the record was by a young student named Randy Gardner. Young Gardner managed to stay awake for 264.4 hours (11 days 24 minutes). I know, I’m not quite sure how he managed it either. Interestingly, in a similar fashion to the participants above, Gardner started to show signs of psychosis during his marathon wakeathon. These promptly disappeared when he eventually slept at the end of the study. Gardner isn’t the only one to attempt to break sleep loss records but the Guinness Book of Records now refuses to acknowledge these given the known risks of extreme sleep loss. Therefore, despite the fact we know of a few instances of this such as a woman claiming to beat the previous record during a rocking chair competition (yup, http://sleep.lovetoknow.com/Record_For_No_Sleep), there are no official reports validating these attempts.

Since Gardner, there were very few sleep deprivation studies which looked at whether sleep loss could induce psychosis symptoms in otherwise healthy people. However, recently, and under a tighter controlled laboratory environment, participants have been sleep deprived for 1-2 days at a time to try to understand and validate these early studies. Unsurprisingly, given these early findings, participants in these studies showed an increase in hallucinations and delusion-like thinking (e.g. feeling more paranoid).

How does this lead into my work?

So, why am I telling you all of this, besides it being incredibly interesting, of course? Well this is where my research fits in. It is all well and good saying there is a link between sleep loss and psychosis but I’m interested in the awkward ‘why’. Why does a lack of sleep produce these symptoms? Are some people more vulnerable to the effects of sleep loss? Does naturally occurring sleep loss (e.g. insomnia) lead to hallucinatory / paranoia experiences and again why might this be? These questions form the basis of my PhD.

What am I currently working on?

My PhD research involves tracking participants’ sleep over long periods of time to see how difficulties in sleep might predict later psychosis experiences in otherwise healthy people. I also track the sleep of those at higher risk for psychosis with a FitBit-like device in order to assess whether pre-existing risk for psychosis makes individuals more vulnerable to the effects of naturally occurring sleep loss. This is important because if those at a higher risk are more sensitive to sleep loss it would highlight the importance of intervening to improve sleep in those vulnerable to developing psychosis. My participants are young adults aged 18-24 years old and it is during this period that a first episode of psychosis can present itself. If improving sleep can be shown to reduce that risk then this is something which can be taken advantage of relatively cheaply.

What is the future of this work?

Recent preliminary studies have highlighted that treating sleep problems in psychosis can lead to a reduction in hallucinations and paranoia (http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(15)00314-4/abstract). This is still early research but if we can understand better the link between sleep loss and psychosis then we can better tailor interventions to help mitigate this. If nothing else, treating sleep within vulnerable populations is a worthwhile target to improve functioning and wellbeing.

So far, my research is still ongoing but I hope to try to understand the mechanisms by which sleep loss can produce psychotic experiences. My final study aims to build on the legacy of classic sleep deprivation studies I started this article with. The hope is that by studying these experiences it might be possible to understand how severe sleep loss might be responsible for strange experiences. In turn, this might have implications for individuals with psychiatric disorders such as schizophrenia further down the line. It is still early days for this research but it is an exciting and fascinating area to study. There are plenty of questions yet to answer and indeed, even ask.

Oh, and for anyone who’s interested, my sleep habits have somewhat stabilised since my undergraduate years…

For the interested

Here is a review which highlights the bulk of the research conducted in my area (http://www.smrv-journal.com/article/S1087-0792(16)00003-4/abstract)

A great video on the effects of sleep deprivation (in case you’re not convinced that losing sleep is bad from this article or from common sense; https://www.youtube.com/watch?v=dqONk48l5vY&t=206s).

An interesting article outlining the importance of sleep (http://www.huffingtonpost.co.uk/entry/the-truth-about-sleep-7-things-learned-from-bbcs-new-documentary_uk_59146817e4b00b643ebbca48)

For anyone struggling with sleep here are some useful resources from sleep experts (https://www.sleepio.com/articles/sleep-tips/)

Finally, for a fictional story about sleep loss which people frequently ask me whether it’s true or not (http://creepypasta.wikia.com/wiki/The_Russian_Sleep_Experiment)

 

This week’s featured PhD…

 

Alex Smith, PhD Student
University of Manchester

 

Who are you?

Untitled

Hello! My name is Alex Smith and I am a 3rd year PhD student at the University of Manchester, UK.

My research is all about better understanding how cells communicate with each other and how the same message can be interpreted in different ways.

 

What are you researching?

Consider human development from embryo to adult. How do cells know which cell type to become and when? And how is the complex process of making a human so reproducible?

To transform from a single fertilised embryo into a human containing roughly 35-40 trillion cells requires a lot of cell-to-cell communication. During development and throughout adult life cells are able to communicate to each other by sending and receiving signals between each other. They tell each other when to divide, when to change cell type and even when to commit suicide (termed apoptosis). The whole process from receiving an informational signal to translating that to a meaningful outcome is termed a signalling pathway.

There are many core signalling pathways required for cells to function normally, but my research focuses on just one; the Notch pathway. The Notch pathway is characterised by the membrane receptor protein Notch, which was first identified in the fruit fly (Drosophila melanogaster) where mutated Notch produces wings with notches.

In short, I’m trying to better understand how the same message i.e. Notch activation can be processed differently by the same cell and the consequences of this in terms of disease.

 

Why study Notch signalling?

Aberrant Notch signalling has been linked to many different cancers. In addition mutated Notch causes other rarer hereditary diseases such as CADASIL. Despite this, there is still much to be learnt about how Notch signalling really works. A better understanding of normal Notch signalling will help understand why things go wrong when Notch causes disease.

At the moment, one route of Notch activation is very well understood but there are other routes which are much less understood. Imagine it as though you are travelling from point A to point B and the most obvious and direct route is to take the highway. But there are likely to be less obvious, smaller roads you could take to get you to the same place. These smaller routes may take longer, but they would be ideal if the highway was closed for some unforeseen reason. You’d still be able to get to your destination. The ‘highway route’ of notch signalling is known in very high detail, but it’s the smaller, alternative routes that are much less well characterised. Ultimately, a better understanding of these smaller routes may provide a strategy for developing better therapeutics for Notch-related diseases i.e. providing a diversion when there’s a block in the road.

 

What do you hope to find?     

There are many questions still left unanswered in the Notch field. I hope to address just a few select questions:

  • How long does it take for Notch to travel down each of the separate routes?
  • Which parts, if any, of the Notch protein control the choice of activation route taken?
  • Do CADASIL mutations bias the route of Notch activation or perhaps slow down the whole process?

 

And what then….?

Hopefully, by better understanding how Notch is activated by the different routes and what influences which route is taken, this will inform how Notch causes diseases such as cancer and CADASIL.

Understanding how cellular communication is compromised by aberrant Notch will hopefully shed light on some new drug targets for Notch-related diseases. That’s the goal!

 

Thank you for reading! Please leave comments if you would like to find out more. Alternatively, the review below details what is known about the less understood (endocytic) routes of Notch activation:

https://www.ncbi.nlm.nih.gov/pubmed/22285298

 

 

This weeks featured research

This months featured Research Boffin!

Who are you?

My name is Dr Hannah Brotherton and I am a postdoc researcher at the University of South Florida…and I am all about the ears and the brain!

Ok, tell me something about your work!

My work involves investigating what is known as the neural gain mechanism in the auditory system in normal hearing people after they wear an earplug for a week or so.

Ok, let me break that down for you. Simply put, I investigate how the activity of the brain, i.e. neural gain, compensates for a hearing loss. To do this, I ask normal hearing individuals to wear an earplug that simulates a high-frequency hearing loss (a very common form of hearing loss in today’s population). I measure their brain activity before and after they wear an earplug to investigate how the brain compensates for the hearing loss.

Give me the bare bones i.e. the background!

Think of it like turning the volume up on a radio when you can’t hear anything. That’s kinda what our brain does in response to a hearing loss.

The brain likes to be active around a set mean level. When you have a hearing loss, the normal level of sensory activity entering the brain is reduced, and as a result this reduces the mean level of brain activity. The brain doesn’t like this and so compensates for the reduction in hearing by turning its own ‘volume’ i.e. neural gain, up.

Gotcha…now give me the bigger picture!

The problem with this, is that in some cases, the brain activity can be over amplified. This is one theory for the development of tinnitus (ringing in the ears) and hyperacusis (an over sensitivity to normally tolerable sounds).

So what do you hope to find?

My research hopes to answer many unanswered questions, which will help build a bigger picture of how this mechanism works

Such questions that remain unanswered are:

  • How quickly does neural gain change after wearing an earplug?
  • How quickly does neural gain recover after we remove the earplug?
  • Does neural gain only change at the frequencies affected by the earplug?
  • What tests are reliable enough to measure changes in neural gain?
  • Is the change in neural gain the same in different age populations?

What does the future hold?

If we can understand how to manipulate the neural gain mechanism, then maybe we can manipulate it in tinnitus and hyperacusis patients

If we can trick the brain of tinnitus and hyperacusis patients into thinking too much sound in now entering the brain i.e. by means of wearing a hearing aid of sound generator device, then we could reduce the abnormally increased levels of neural gain and potentially alleviate some of the symptoms of tinnitus and hyperacusis.

It’s a pretty neat idea, and its gaining more and more interest in the field of tinnitus and hyperacusis.

If you want to find out more about Hannah’s research, leave a comment below. You can also find out more about of her work, tinnitus and hyperacusis from the links below.

Thank you for reading!

Interesting links:

For a spot of light reading, here is a review article that talks about the research Hannah is interested in:https://www.ncbi.nlm.nih.gov/pubmed/26139435

Also, here are some helpful tinnitus and hyperacusis information links:

https://www.tinnitus.org.uk/

https://www.tinnitus.org.uk/hyperacusis

Welcome to the launch of the official PhD SOS website

A PhD is one of the most rewarding things in an academic’s life, but it can also be one of the most difficult times in your life. A PhD is more than just a degree, it is a life experience, so be open and welcoming to the whole process. However, that’s easier said than done. So…if you are finding the journey difficult, I hope that you find PhD SOS helpful!

During my studies, I created a pool of resources that helped me get through my PhD. Many of the resources that I will share with you, here at PhD SOS, are resources that worked for me and my PhD, so please be aware that some posts may not be as relevant to you as others, and you may not find everything useful.

If you do find anything that PhD SOS posts useful, please remember that your main source of support and advice should come from your academic supervisory team. Please do not use any information or advice from this website as a substitute to the academic and pastoral support you are receiving from your institution (please see disclaimer).

If you are finding a PhD difficult, stick with it, work hard, work smart, and enjoy the journey of getting your PhD!

Our hope for PhD SOS is to become an online community for PhD students to communicate and share tips and advice with each other.