Hello and welcome to my blog! My name is Caroline and I am a PhD student at the University of Sheffield. My research project focuses on Striga - a genus of parasitic plants that devastates harvests by infecting food crops. I am exploring the defence reactions that can make host plants more resistant against Striga. Due to my ongoing battles with anorexia, I haven't made as much progress as I would have liked but I am determined to finish the course.

This blog charts the ups and downs of life in the lab, plus my dreams to become a science communicator and forays into public engagement and science policy....all while trying to keep my mental and physical health intact. Along the way, I'll also be sharing new plant science stories, and profiles of some of the researchers who inspire me on this journey. So whether you have a fascination for plants, are curious about what science research involves, or just wonder what exactly I do all day, read on - I hope you find it entertaining!

Tuesday 23 July 2013

IUPS 2013 The Public Lecture: The Rhythms of Life – What your body clock means to you from eye disease to jet lag

'We think we are the same creature throughout the 24 hours of day. We're not, we're fundamentally different...we are an extraordinarily dynamic creature, constantly changing and that impacts how we construct our society'.

Speaker: Professor Russell Foster, Professor of Circadian Neuroscience at Oxford University and a Fellow of the Royal Society. A passionate advocate for communicating science to the public, with a strong YouTube presence.

The impact of body clocks and sleep regulation on our everyday functionality... A more inclusive topic for a public audience would be difficult to find. We all know that sleep is important and many of complain  that we suffer a lack of it, yet this behavioural habit, which makes up around 36% of our life, remains a mystical realm that eludes understanding. Robert Foster provided a stimulating exploration that emphasised how we constantly undermine the value of slumber.

Professor Foster opened his lecture with an introduction to the endogenous body clock, demonstrating that different aspects of our physiology, such as body temperature, alertness, growth hormone levels, peak at different times of the day. These natural ocissilations, he explained, are endogenous and would be maintained even if we took up refuge in a permanently dark cave system. Not surprisingly, these variations have functional consequences. Core body temperature shows an approximate one degree fluctuation over 24 hours, reaching its lowest level at night, before climbing in anticipation of waking in the morning. This is thought to explain why swimmers are, on average, 2.7 seconds slower over 100m at 6 'o clock in the morning compared to 8 'o clock at night - I wonder if this has any influence on deciding when to hold competitions or training sessions. Blood pressure shows a similar rhythm, rising in anticipation of waking. Clinical studies have found that this is correlated with a 49% increased stroke risk between 6 am and 12 noon, prompting Foster to comment that each day you should rejoice each afternoon for you have 'survived the most dangerous part of the day'. 

Cognitive performance is another area highly related to sleep patterns; we all know that we perform less ably when sleep deprived but the reality appears to be more complex. In one study, cognitive ability was assessed in individuals at different parts of the 24 hour cycle. Frighteningly, performance at 6 'o clock in the morning was WORSE than the level expected for a blood alcohol concentration of 0.08% ( the legal limit for driving). Because the participants were kept awake until they were tested, it could be argued that poor performance was due to fatigue. Bizarrely though, those tested at 10 ' o clock int he morning performed BETTER than those at 6 ' o clock, despite missing more sleep. So perhaps you should be more worried if someone offers you a lift in the early hours rather than if they are under the influence...

Having established the existence of these endogenous rhythms, Professor Foster Proceeded to describe how they are produced. The main orchestrator of the body clock is the supra chiasmatic nucleus (SCN) in the brain; although this is composed of billions of single cells, each one is capable of generating 24 hour oscillations, hence this mass of individual clocks are coordinated together to make the 'master' body clock. Tying in nicely Sir Paul Nurse's lecture describing living organisms as information systems, Professor Foster outlined how 24 hour rhythms are driven by a conserved set of clock proteins operating in a feedback loop. The proteins produced by clock genes act as transcriptional activators for genes involved in metabolic processes however they also translocate into the nucleus and turn OFF the original clock genes. This causes the concentration of clock proteins to decrease ( as the existing proteins are degraded in the cytoplasm), reducing the inhibition of the clock genes until they can become active again.  Subtle modifications in clock gene proteins are being linked to distinct sleep patterns such as 'morning' and 'evening' sleep types, demonstrating their central significance.
 Are we thus driven by our genes? Does is master clock FORCE a 24 hour rhythm on all the other organs? 
NO... A key development in circadian research was the discovery that ALL cells in the body can generate a 24 hour rhythm. So...why have an SCN at all? It clearly has a fundamental importance as it's destruction ( for instance, by a tumour) results in all 24 hour rhythms being abolished. It seems that the SCN functions as the grand conductor of an orchestra composed of billions of individual cells, and provides a regular tempo for each cell to refer to. As Professor Foster summarised, this enables the body to produce 'a glorious symphony...rather than a cacophony of sound'. 

Following on from this succinct summary of how sleep/ wake patterns are produced, Professor Foster moved on to explore the importance of sleep in our functioning and society. Sleep, he argued, has become undervalued in recent times. Traditionally, it had been viewed as an essential, restorative behaviour worthy of diligent practice; as Benjamin Franklin said 'Early to bed, early to rise, makes a man healthy, wealthy and wise'. There was however, no scientific evidence for this argued Professor Foster, allowing sleep to viewed in an increasingly negative manner over the modern era, culminating in a view best summarised by Thomas Edison 'Sleep is a criminal waste of time and a heritage from our cave man days'. Many of us are guilty of 'burning the candle at both ends', feeling a pressure to rise early and end our working days late. Yet scientific research suggests that sleep has important roles in cellular repair and brain function, particularly laying down new memories. The human endogenous rhythm, however is longer than 24 hours; if this was not reset daily, we would rise later and later, becoming out of synch with the light/ dark cycle. The signal for entrainment appeared to be natural light as removing the eyes prevented sleep/ wake cycles from being maintained. Hence the eye is a dual function organ, forming images and perceiving brightness. The process of image production using rods and cones has long been known, yet in mutant mice whose rods and cones have degraded, sleep patterns are not disturbed; as Professor Foster summarised 'these mice are visually blind but not clock blind'. This suggested the existence of a novel photoreceptor - a furious controversy among ophthalmologists at the time, who had been studying the inner eye structure for 150 years. Foster persevered in his reasoning however and was eventually proved right with the discovery that 1 in 100 of the ganglion cells that connect rods and cones are photo receptive - now known as photosensitive retinal ganglion cells. This knowledge helps to explain how in certain diseases, such as diabetic retinopathy, patients may be essentially blind but show natural sleep/ wake patterns. In addition, it can be used to improve advice for such patients- rather than wearing dark glasses, patients ought to expose their eyes to natural light to re- set their endogenous clocks. In this light, giving glass eyes appears almost criminal as it replaces a partially functioning organ with a dead, totally useless vehicle. 

So, what implications do these insights in circadian rhythms have for everyday society? Professor Foster was keen to stress how a 'whole cocktail' of neurotrasmitters is involved in regulating sleep patterns, making sleep very susceptible to disruption. During our waking hours, sleep pressure accumulation is thought to be mediated by adenosine- normally the body clock mechanism prevents this from inducing sleep until the correct time. Many of us are at war with our clocks, however, using alarms to jerk ourselves awake and caffeine ( which blocks adenosine receptors) to fight off fatigue. This results in a vicious 'stimulant-sedative' cycle. We do not allow natural light to harmonise our internal rhythms, flooding our bedrooms with harsh lights, bright technology and entertainment. As Foster argues, we could sleep better if we cleaned our teeth before bed in semi- darkness.  This is poor comfort for shift workers, who are denied access to natural light rhythms ( the best advice seems to be 'don't do shift work'). Other practical measures are to avoid caffeine ( which has a half life of 5-9 hours) after lunchtime and not to nap for more than 20 minutes in the day - any longer would counteract the sleep pressure that helps us nod off at the opportune time. Chronic sleep deprivation is a major epidemic, rarely noticed except when it is implicated in disasters such as the 2010 Air India crash. As scientific evidence for detrimental health effects increases, however, people may become prompted to take better management of their sleep patterns. For one thing, sleep deprivation affects the balance of the satiety hormones Ghrelin and Leptin; the former stimulates apeptitie whilst the latter suppresses it. Chronic sleep deprivation tips this balance in favour of ghrelin, supporting the argument that lack of sleep can predispose to obesity. Deprived sleep can also amplify the stress pathway and elevate cortisol levels: this has myriad implications including suppressed immunity, hypertension, gastric acid production and glucose:insulin imbalances. More disturbingly, sleep deprivation is now being implicated in many mental health conditions as scientists move from the view that disturbed sleep is the result of anti- psychotic medication towards an argument that it may actually be a primary cause of these diseases. Psychological illnesses, such as schizophrenia, and sleep regulation appear to share common neural pathways and experimentally disrupting genes affecting sleep/ wake cycles impacts mental health. Meanwhile, improving sleep patterns in human patients has had some success in improving mental illness symptoms. Sleep may thus prove an effective therapeutic target in these cases.

As Professor Foster stated 'we are now on the point of understanding the fundamental neuroscience of these systems'. So how can this be put into useful practice? An example is provided by a study on teenagers, which found that the teenage clock is intrinsically delayed by 2 hours; whilst the average adult becomes fully alert by 10 'o clock, most teenagers take up to 12 ' o clock to do this, with 10-20% only becoming fully awake at 2 'o clock. In an intriguing experiment, cognitive function in adults showed a 7% decline between mid- morning and mid- afternoon, whereas teenagers showed a 10% INCREASE in function. Could this explain why teachers find it easier to control ( tired and subdued) classes in the morning compared to ( boisterous and rowdy) classes in the afternoon? Perhaps the whole school day should be restructured as in Monkseaton School in Newcastle. When the school adopted 10 o' clock starts, the GCSE scores showed a marked improvement, particularly among socially disadvantaged children. 
As these examples show, better understanding of our circadian rhythmns, the harmonious counterpart to our conscious disorder, could help us to structure our daily lives and societies to enable us to function most optimally and enjoy long term health. This fascinating lecture has certainly made me examine my own lifestyle more closely (should I stop using my iPAD in bed?). But the audience clearly had other concerns on their minds- when the floor was opened for questions, the first was 'Has the Royal Baby been born yet?'

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