Tuesday, 27 March 2012

Shedding Light on Body Clocks & Brains

Last week, on a sunny Friday afternoon I was in the basement of a UCL building performing my first public talk on my PhD and the effect of light on body clocks. This was the last session of Bite-sized lunchtime lectures this term, which allow early career researchers at UCL to talk about their research interests to the general public.

By the time I took to the stage the room had standing space only, a really successful turn-out. We even had a class of biology students from Norway! Apparently, my nerves were only noticable when I held the 96-well plate and you could see my hands shaking. Quite lucky really, as I felt like I was shaking like a leaf the entire way through.

After the presentation I got some really good questions, which I will re-type up here for everyone's benefit.

A huge thank you to the Bite-sized team for their help and feedback: Hilary, Kim, Laura and Matthew. Thank you also to Simon, who had to hear the presentation a few too many times! Thanks also to those who came and supported me.

And for those of you who missed it, or want to see it again, here it is:

0:00 Intro to talk
1:44 Chronotherapy - asthma & cancer
2:36 How body clocks work
4:35 Using light to help our body clocks
6:25 Zebrafish - development, regeneration and cancer research
7:44 My PhD research
9:40 Glowing zebrafish
10:34 Rhythms in light sensitive zebrafish brains
11:49 Conclusion

Questions - please feel free to ask more in the comments section below

As rats are nocturnal, how does testing drugs on them during the day effect them?
This is a really important point. Not all drugs are effected by time of day, but a lot of them are, and unfortunately a lot of pharmaceutical companies only test for drug effects (and side effects) during the day, which is the rat's sleeping time, not during the dark phase, when the rat's are more active. So the results are be more aligned with giving humans drugs during the night, which happens less frequently.

A few drugs have been deemed to toxic when trialled during the day, when they can be less toxic and effective during the night, and so we are losing drug candidates.

Does period3 have any other role in the zebrafish?
Period3 is a gene that signals time of day information throughout the cell, we don't know of any other role it is playing in the cell.

How did you measure gene expression, when you weren't doing the bioluminescent recording?
Good question. I mushed up the brain, to break all the cells open, and allow access to the messenger RNA molecule. This is an intermediate molecule we can measure when the gene is being expressed into protein.

We can determine how much messenger RNA is in the brain by using qPCR, quantitative polymerase chain reaction. This effectively doubles the amount of the RNA exponentially until enough can be detected, and then we can work backwards and find out how much we had to begin with.

How long can a zebrafish brain stay in culture? Will it behave in culture the same as in the body?
That's a good point. I've kept zebrafish brain regions in culture for two weeks, and the rhythms are still strong, so I think they could go for longer without any change in media. Eventually, the nutrients in the media will get used up, and the waste products will build up and so the cells will die. However, biologists can keep cells alive for decades by replenishing the media and giving the cells space to grow.

Cells and brains and other tissue cultures won't necessarily be the same in culture as they are in the body, so we try where possible to examine rhythms in both.

If light exposure during the day is so important, should schools be getting students to spend more time outside and less inside in the classroom?
Sometimes staying indoors can't be avoided, and that's why using effective lighting indoors is important. However, where possible everyone should try and spend enough time outdoors, from young people to the elderly.

How long is enough time outside?
It can vary from person to person, and on the time of year, but as a rough estimate I would aim for a couple of hours.

Is this also effective for jet lag?
Yes, light in the morning of your destination will help you synchronise to the new time zone quickly. A bike ride in the morning has been shown to be most effective, perhaps not what you really want to do to recover from a 12 hour flight, but you'll thank me later.

What does this light research mean for people with disabilities/limited vision?
The cells in the eye that are responding to this blue light are actually not the rods or cones or cells commonly associated with vision. So you can have blind people, who are visually blind, but not time blind. Their eyes can still use light to synchronise their body. Therefore, exposure to light is important for everyone including the disabled.


Enjoy this blog post? Check out my other posts from body clock related Bite-sized lunchtime talks:
Clocks make you fit, evolutionarily speaking and UCL researchers are mapping our happiness across the week

Monday, 12 March 2012

Is Daylight Savings costing us lives?

Next week, on Sunday March 25th, the clocks will spring forward an hour for Daylight Savings. Other than having an hour less in bed, and feeling a bit more sleepy in the week, can this have any other significant effect on our body clock? Can it cause you to have a heart attack?

Research published this year has looked at the effect of Daylight Savings on the number of people suffering acute myocardial infarctions (heart attacks) in Sweden [1].

Blood pressure is a component of the body clock, dipping low at night naturally. Heart attacks are far more likely to occur in the morning when your blood pressure is rising. Can altering the timing of the body clock by just one hour have such a profound effect on your heart as to cause a heart attack?

Heart attacks are linked to the body clock, being more likely to occur in the morning  © Grewlike

In 2008 the group showed that in the week following the transition into Daylight Savings the number of people going into hospital with heart attacks did increase [2]. In that study they analysed hospital admissions over 19 years, comparing the fortnight before with the fortnight afterwards.

In their latest study they repeated the analysis on data collected from 2007 from 74 hospitals, covering 95% of the coronary care admissions in Sweden. This data was more detailed, so they could find out who were more at risk.

As well as age and gender, there was information on other heart attack indicators such as cholesterol levels, BMI, smoking history, diabetes, high blood pressure, history of heart problems, other heart attacks etc.

When they analysed this new data, they observed the overall increase in heart attacks again. There were higher rates of heart attacks in the week following Daylight Savings. The increase measured was smaller than the first study, however still significant (and therefore still a risk).

More heart attacks occur in the week after entering Daylight Savings Time (DST) in the Spring © Janszky, 2008 

Those at higher risk in this Spring week included all those on preventative medication, including aspirin, calcium channel blockers and statins.

Remarkably, those who had a high cholesterol and high triglyceride (fat) levels seemed to have less heart attacks. This was unexpected, but the researchers point out that they have no information on the sleeping and activity levels of this group.

It could be those who are protected in this week are more sedentary, sleep more, and become less sleep deprived than the rest of the population. Further information on the link between sleep, the body clock and heart attacks could determine what advice can be given to those vulnerable of having a heart attack.

With 1.5 billion people (close to a fifth of the world's population) being influenced by Daylight Savings, a small increase in the number of heart attacks can have large ramifications. Governments, scientists and society really need to investigate their motives for having daylight savings.

In the meanwhile, take it easy next week!

Enjoy this blog post? Check out: Double Summertime: Double trouble? and Using time of day to reduce heart damage in breast cancer treatment

[1] Janszky, I., et al. (2012). Daylight saving time shifts and incidence of acute myocardial infarction - Swedish Register of Information and Knowledge About Swedish Heart Intensive Care Admissions (RIKS-HIA). Sleep medicine. Elsevier B.V. doi:10.1016/j.sleep.2011.07.019

[2] Janszky, I., & Ljung, R. (2008). Shifts to and from daylight saving time and incidence of myocardial infarction. The New England Journal of Medicine, 359(18), 1966-8. doi:10.1056/NEJMc0807104

Friday, 9 March 2012

ADHD: Sleep and Body Clocks

Over 50% of adult attention deficit hyperactivity disorder (ADHD) sufferers report on-going sleep trouble, with 27% of suffers fitting the criteria for chronic insomnia [1]. In the past few years several studies have looked at the relationship between sleep, the body clock and ADHD. Does ADHD cause sleep problems? What can be done to help?

There are many ways to monitor rhythms in human body clocks. We can look at an individual's sleeping patterns, their hormone levels, and even their genes. We've already mentioned that sleeping problems are significantly linked to ADHD, but as we examine these other body clock markers we can see how deep the problem lies.

Cortisol, the stress hormone, is released at higher intensities in the night (see post on asthma). In ADHD patients whilst they maintain a daily rhythm in cortisol, the peak shifts to later in the day, effecting their sleep at night.

The rhythm in cortisol occurs later in ADHD patients (C) Baird et al 2011

Some of the clock genes, which are used to signal time of day information throughout all the cells in the body, were also found to not be functioning at all in the ADHD patients tested [2].

All this evidence combined shows that it is not just sleep that is a problem with ADHD, but there are underlying issues with a dysfunctional body clock. In fact, the more severe ADHD rating a patient had, the weaker their body clock rhythms were.

Melatonin is a hormone that is released at night, induces sleepiness, and communicates time of day information around the body. Melatonin is produced much later in chronic insomniac ADHD sufferers who stay awake at night.

Luckily, melatonin can be taken as a pill (it is often used to help overcome jet-lag). When taken at the correct dosage and time of day, melatonin can fix broken body clocks and improve sleep patterns.

Melatonin, a sleep-inducing hormone, is being used in trials to treat insomnia in ADHD (C) 

A few small trials have reported significant benefits in using melatonin to treat insomnia in ADHD sufferers. In one trial with approx 100 children, after 3 years, 88% recorded improved sleep at night. They were also able to perform better during the day, both mentally and physically [3].

Daily melatonin intake led to no serious side effects in this trial. However, only 9% could stop the melatonin treatment without reverting back to suffering insomnia, so the treatment needs to be continued long term.

Parents' responses after a 3 year follow up when using melatonin to treat ADHD (C) Hoebert 2009 

Melatonin is one method to realign a person's internal body clock to the external day, and is showing positive benefits in ADHD sufferers day to day lives. With the amounting evidence of the relationship between ADHD and a broken body clock there will hopefully be trials conducted in adult ADHD patients and more treatments available.

Please note, I am not a medical doctor and cannot advise ADHD patients on melatonin treatment. However I would love to hear from you if you have ADHD and sleep problems. Please write in the comments box below.

Enjoy this blog post? You may want to check out Nocturnal Asthma or Around the Clock Doc.

[1] Coogan, A N. et al (2012). Adult attention deficit hyperactivity disorder: translating research into practice. Attention deficit and hyperactivity disorders, 41-51. doi:10.1007/s12402-012-0073-7

[2] Baird AL, et al (2011) Adult attention-deficit hyperactivity disorder is associated with alterations in circadian rhythms at the behavioural, endocrine and molecular levels. Mol Psychiatr. doi:10.1038/mp.2011.149

[3] Hoebert M, et al (2009) Long-term follow-up of melatonin treatment in children with ADHD and chronic sleep onset insomnia. J Pineal Res 47(1):1–7. doi:10.1111/j.1600-079X.2009.00681.x

Thursday, 1 March 2012

Sleepless Bees

Human babies need a lot of sleep, but as they grow older their body clocks and sleeping habits will change. Other animals also change their body clocks with age. One extreme example is the Honey Bee, Apis mellifera.

The phrase "busy as a bee" is truly deserved in these youngsters. At only 3 days old the infertile females are put to work as "nurse" bees. They feed larvae and are active around the clock without any sleep - for 9 days!

Brains of nurse and forager honey bees were examined for daily rhythms in gene expression (C) Goshzilla Dann, 2008

The infertile honey bee females go through several roles in their lifetime. At 11 days the nurse bees will mature into different worker roles in the hive. At 3 weeks old they become "foragers" with highly rhythmic behaviour: pollen hunting during the day and sleeping at night.

A recent study has looked at the genetics behind the body clocks of the honey bee [1]. They compared the levels of gene expression in the non-rhythmic nurses with the rhythmic foragers. Were there any rhythms remaining in the nurses?

Nurse bees work around the clock without sleep for 9 days (C) Max

The genetic analysis showed that whilst 4% of genes were rhythmic in the foragers brains, only 1.5% were in nurses. Genes in the visual system and the core clock genes did not oscillate in the nurses. However, there were genes involved in energy metabolism that remained rhythmic.

When nurses were taken away from their hive and isolated, they became diurnally rhythmic, being more active during the day. This suggests that their working-around-the-clock behaviour is in part due to their hive environment or association with other bees. However, there are still some underlying rhythms in the nurses that aren't lost even when their behaviour is arrhythmic.

When the nurse bees grow older they take on different roles, as foragers they are highly rhythmic (C) JR Guillaumin

The honey bee represents a useful animal to understand how body clocks can change with age. Like cavefish they show how a body clock can tick quietly in the background. However, I won't be attempting to stay awake for 9 days straight to test this directly!

Enjoy this post? You might also like Old Fruit Flies and Broken Body Clocks and Young or old: who can stay awake better at the wheel?

[1] Rodriguez-Zas, S. L., et al. (2012). Microarray analysis of natural socially regulated plasticity in circadian rhythms of honey bees. Journal of Biological Rhythms, 27(1), 12-24. doi:10.1177/0748730411431404

Thursday, 23 February 2012

Old fruit flies and broken body clocks

Sleeping problems can get worse with age but they are often exacerabated in age-related diseases that involve damage to the brain such as Alzheimer's, Parkinson's and Huntingtons Disease [1]. Why does the body clock get disrupted? Indeed, is a disrupted body clock the result or the cause of these diseases, or a bit of both? Could a fully-working healthy body clock protect against these brain diseases?

A recent study in fruit flies being published next month aimed to address some of these questions [2]. The fruit fly has a body clock with behavioural rhythms and many similar genes to the human body clock. They also can suffer brain related ageing diseases, and as they typically only live for 2-3 months it doesn't take too long for researchers to study these.

Fruit flies (Drosophila Melanogaster) who live for 2-3 months are being used to study the effect of the body clock on age related diseases (C) Marcos Teixeira de Freitas

The researchers have certain fruit flies where a specific gene known to act in protecting the brain is removed, these flies die younger due to brain defects. They also have flies that don't have a functional body clock, these are lacking a gene called "period" and causes the fly to have no body clock rhythms, in gene expression or in behaviour.

They wanted to determine the effect the body clock has in protecting the brain from age-related diseases. Therefore they took their mutant flies that suffer age-related brain damage and bred them with the flies that have no body clock. 

What they saw was that if you take away the body clock from a fly that has age-related brain damage, they die even younger. So a functional body clock is being protective against these age-related brain diseases. 

Fruit flies that are prone to old age brain disease are more likely to die younger if their body clock is disrupted.   Adapted from Krishnan, 2012

To rule out any effects of the gene "period" working in another way other than to maintain a healthy body clock they also tested the effects of raising the age-related brain defect mutant fruit flies in constant light. Constant light also stops behavioural rhythms and the molecular body clock.

Stopping the body clock with constant light also caused the brain damage to be worse, so it wasn't due to other functions of the period gene.

This research doesn't fully resolve the question of the cause or effect of a disrupted body clock in age-related brain diseases, though it does suggest it to cause the brain damage to be worse.

However, the results do show how maintaining a healthy body clock can increase chances of survival in animals prone to age-related brain diseases. My hope is that research in this field will further our understanding of human ageing.

Enjoyed this post? Check out Young or old: who can stay awake better at the wheel? and Around the Clock Doc

[1] Vitiello, M. V. "Sleep and Circadian Rhythm Disorders in Human Aging and Dementia", Encyclopedia of Neuroscience, Pages 887–893

[2] Krishnan, N., et al., "Loss of circadian clock accelerates aging in neurodegeneration-prone mutants", Neurobiology of Disease, Vol 45, Issue 3, March 2012, Pages 1129–1135, doi:10.1016/j.nbd.2011.12.034

Thursday, 16 February 2012

Young or old: who can stay awake better at the wheel?

Following on from my blog post last week, I looked at other research on driving being published by researchers at Loughborough University. Their second paper this year has looked at who could cope better with boring afternoon driving after a bad night's sleep, old men or young men [1]

I realize this is going to be a controversial topic, comparing driving abilities of old and young men, and the results may (or may not) be surprising. The aim of the researchers is to improve information given to drivers, and not (that I am aware of) to influence insurance companies.

Why do this study on male drivers? In the UK 90% of sleep-related accidents involve male drivers. Most afternoon sleep-related accidents involve older drivers, are they more prone to fall asleep at this time of day and therefore need specific advice to avoid these accidents?

Men from two age categories were selected; young 20-26 years old, and old 52-74 years old. All were experienced drivers, driving for more than 3 hours each week for at least the past 2 years. The drivers came in to the lab twice: after a normal night's sleep, and two weeks apart after a restricted to 5 hours sleep.

Drivers drove for a montonous 2 hours in a simulator like the one above (C) Alan in Belfast

This time they all had a light lunch before starting their 2 hour monotonous drive in the simulator. Drivers stayed in the left hand lane, at a steady speed, occasionally overtaking. Whenever the driver drove onto the "rumble strip" on the hard shoulder an "incident" was recorded. EEG (brain activity) and eye movement were monitored to determine when this lack of concentration was due to sleep, as opposed to being distracted. Drivers themselves were also monitoring how sleepy they felt.

The results showed that in fact younger drivers were more prone to having sleep-related incidents than old men at this time of day. This becomes significant after 30 minutes of driving and remained significant for the rest of the test. Young men were also more sleepy than the older men, from both their EEG patterns and their self-reports.

Young drivers were more prone to sleep-related lane crossing than older drivers
 in monotonous afternoon  driving after a short night's sleep. Adapted from Filtness, 2012

So are older men in fact better at driving when tired? This conclusion would agree with many other studies done looking at night time driving in different age groups [2]. Young men have more incidents during night time simulator driving and this corresponds with the road statistics  (I did lose an argument with my University professor trying to counter this, he had more data on his side).

Encouragingly, both groups were able to accurately rate their sleepiness, which correlated well with the EEG measurements. The older group were slightly better at this then the younger men, but both groups did realise they were sleepy.

So why are older men more likely to have an accident on the road in the afternoon? The data shows they are better able to cope with being sleepy. Unfortunately there are no statistics to show the percentage of different age groups on the road at different times of day, only those who are in accidents, so one possibility is there are just more older men on the roads in the afternoon.

The one flaw to this study is that using a simulator might not be as accurate as on the road, as the simulator may exaggerate any sleep related incidents, as there is no real risk to the driver. However, it would be unethical to do this test scientifically with drivers on the road.

Overall, this is an excellent study to address what is causing the sleep-related accidents on the roads. It really highlights the need for researchers to record driving effects for longer than 30 minutes. For advice on driving and when to take breaks and naps, please check out their website Awake.

Enjoyed this blog post? Check out Poor Sleep and a Large Lunch Effects Driving and Red Sky at Night, Sleepers Delight

[1] Filtness, A.J., Reyner, L.A., & Horne, J.A., Driver sleepiness—Comparisons between young and older men during a monotonous afternoon simulated drive. Biol. Psychol. (2012), doi:10.1016/j.biopsycho.2012.01.002

[2] Campagne, A., Pebayle, T., Muzet, A., 2004. Correlation between driving errors and vigilance level: influence of the driver’s age. Physiology & Behavior 80, 515–524

Tuesday, 14 February 2012

Happy Valentine's

Yesterday a friend asked me whether I was going to blog about Valentine's Day, well I wouldn't like to lose my reputation of being able to link body clocks to absolutely everything (they are pretty universal). So, I pondered whether there could be a good biological reason to celebrate Valentine's Day in February.

I first looked in the Body Clock Guide which has a whole chapter dedicated to the best times to make love. One study in it looked at the love lives of 5 Parisian men in the 1970's [1]. They examined the levels of testosterone and other hormones as well as activity for 14 months.

During October there was a rise in testosterone corresponding to love making activity, which then dipped over 6 months. So maybe, Valentine's Day is just what we need in February!

A young couple in love in Paris (C) Simon Moore, 2007

Many of the other studies looking at the best time of day to make love but on the whole have been limited by small number of participants and accuracy. There's not been many recent studies, so I presume it's quite hard to get scientific funding for these trials. However, the results tend to show peak times of day are when it's most convenient, between 10pm-1am being most popular.

Perhaps more accurate data will come out of apps like Mappiness, where you can state making love as an activity option when it beeps you to find out where and how happy you are.

Happy Valentine's Day!

[1] Reinberg, 1978, "Circadian and circannual rhythms in sexual activity and plasma hormones (FSH, LH, Testosterone) of five human males" Archives of Sexual Behavior Vol 7, No. 1, pg 13-30, DOI: 10.1007/BF01541895

Thursday, 9 February 2012

Poor sleep and a large lunch increases risk of a car accident

There's a lot of anecdotal evidence that would suggest that if you've had a bad night's sleep and you've got an afternoon full of boring dual carriageway driving ahead of you, it's probably not the best idea to have a large lunch. Well now there is the scientific data to prove it.

Researchers at The Sleep Research Centre at Loughborough University have recently published their results looking at the effect of eating a large lunch on afternoon driving ability [1]. It is the first of it's kind to look at long montonous driving in the lab. Most studies have only analysed the first 20 minutes and others were limited by examining non-driving skills such as psychologocial performance tests, which have come up with confusing results.

Experienced drivers who normally sleep well were recruited to perform monotonous afternoon driving in a simulator. In the simulator the drivers had to stay in the left hand lane, at a steady speed and would occasionally have to overtake slow drivers, to avoid collision. They were asked to drive for 2 hours without taking a break, the maximum time advised by UK road safety organisations.
Monotonous afternoon driving on a dual carriageway was simulated to look for
incidents of sleep-related lane deviations (C) fras1977, 2009
The study aimed to find out when they were falling asleep at the wheel. This can happen for seconds without the driver knowing they are falling asleep. Whenever the driver drove onto the "rumble strip" on the hard shoulder an "incident" was recorded. EEG (brain activity) and eye movement were monitored to determine when this lack of concentration was due to sleep, as opposed to being distracted.

The drivers were required to sleep well for 3 days and then the night before the experiment to restrict their sleep to 5 hours. Coming into the lab they were given lasagne and a yogurt, either a calorific meal or a light lunch. Both looked the same, in the same packaging, but one was 922 calories with lots of fats and carbs whilst the other was only 305 calories, and the subject didn't know which one they were eating. Then they were then sat down to drive for 2 hours in the driving simulator.

After 30 minutes of driving there was no difference between the number of "incidents" (driving on to the rumble strip due to drifting off to sleep). However at all times between 30 min - 2 hours of driving those who'd had the heavy meal were drifting off the road more.

The number of "incidents" (driving out of lane due to sleep) is increased in those who have had
a heavy lunch, EEG also shows their increased sleepiness. Adapted from Reyner, 2012

So this confirms what common sense would dictate, eating a heavy lunch after a bad night's sleep damages your ability to drive safely for long montonous car journeys in the afternoon. However, this was still an important study to perform.

The results of this experiment will improve the advice given to road users. Further information about their research, advice and services can be found at here. And, if you were concerned about whether the drivers got home safely after falling asleep in the simulator, don't worry, they were all taken home in a taxi.

[1] Reyner, L.S., Wells, S.J., Mortlock, V., & Horne, J.A. (2012). “Post-lunch” sleepiness during prolonged, monotonous driving - Effects of meal size. Physiology & behavior, 105(4), 1088-91. Elsevier Inc. doi:10.1016/j.physbeh.2011.11.025

Thursday, 2 February 2012

Using time of day to reduce heart damage in breast cancer treatment

A new paper this month suggests that treating breast cancer patients with radiation outside of the hours of 6am to noon will reduce side effects that could damage their heart [1].

Radiotherapy treatment has already been improving rapidly in many ways, to ensure that the tumour recieves the correct dose of treatment, whilst sparing the normal healthy tissue. However, radiation still carries an immediate and a long term risk of damage to the heart. Dr Gupta and his colleagues at the Department of Radiation Oncology in the Tata Memorial Cancer Centre in India, suggest that the correct timing of radiation treatment could minimise these risks further.

Radiotherapy is a common treatment for breast cancer, however one side effect is heart damage (C) CANCERactive 2012
With the significant improval in survival rates of breast cancer patients it has become even more important to minimise any long term effects of radiotherapy. Currently, in England and Wales, more than 70% of women diagnosed with breast cancer will live for at least 10 years, and it is predicted that 64% will live for at least 20 years [2]. Critical coronary artery disease can occur 10-15 years after radiotherapy and so it is vital that these long term effects are analysed.

Oxygen demand in the heart muscle is higher in the morning (6am and noon) but the supply of oxygen is lower. Unsuprisingly, this corresponds to when most heart attacks occur and when the heart is most prone to injury. Many other biological functions are occurring at this time of day that puts the heart at risk to damage: blood pressure is rising, adrenaline and other neurotransmitters are increasing, and people are becoming more active, putting more demand on the heart.

Dr Gupta suggests by avoiding radiation therapy in the morning in breast cancer patients, especially those receiving treatment in the left side, they will avoid short term and long term damage to the heart.

However, most radiotherapy treatment is now precisely targeted to the breast tissue (some radiotherapy machines can be precise to sub-millimeter), and there is speculation as to whether the surrounding heart tissue is effected [3]. It should be highlighted that to date there has been no analysis of the incidence of heart problems in breast cancer patients with standardised timing of radiotherapy, and therefore this is currently still a hypothesis.

Robust trials are certainly needed to address this issue, but the hope is that by using circadian timing, the side of effects of cancer treatments can be minimised whilst still allowing the treatment to be effective in removing the cancer.

Please note, I'm not a medical doctor, if you have breast cancer then you can speak to your doctor about timing your treatment. The above article is talking about a medical hypothesis (an idea) that has yet to be tested. Many cancer patients also have a desynchronised body clock, which can make it hard to pinpoint the perfect time of day to give treatment, and different treatments might have different times of day when they are more effective/less harmful. I hope you find my blog posts helpful in explaining the latest research and research ideas. Feel free to add a comment and I will try and answer any of your questions.

[1] Gupta D et al. Cardioprotective radiotherapy: The circadian way. Med Hypotheses (2012), doi:10.1016/j.mehy.2011.12.009

[2] Cancer Research UK website, CancerHelp UK, Breast Cancer Statistics and Outlook, accessed on 28-1-2012

[3] Breastcancer.org Response to "Radiation for breast cancer ups heart disease risk", accessed on 28-1-2012

Saturday, 28 January 2012

Clocks make you fit, evolutionarily speaking

Yesterday I attended the Bitesize lunchtime lectures at UCL and once again really enjoyed both the talks. Andy Beale gave a great introduction to the body clock field and his own research using a blind cavefish to investigate the evolutionary importance of body clocks.

This was Andy's first public engagement lecture at UCL. His intro "why we should care about body clocks" had photos of Andy himself sleeping (sleep-wake cycle), in a plane (jet lag), and drinking alcohol at lunchtime (which will get you more drunk than in the evening). The audience were laughing and certainly engaged.

Andy uses jet lag as an example of how we can disrupt our body clock (C) Andrew Beale, 2012

Andy gave examples of many other species that have body clocks, from the parasite that causes malaria, to the sleeping lion. Andy's interest in body clocks stems from his interest in evolution, what is so advantageous about having a body clock that it would be found so universally in so many diverse creatures? Does the early bird catch the worm?

Evolution is driven by natural selection, Darwin's "survival of the fittest", and in this instance it can be concluded that "clocks make you more fit". Being able to predict the sunrise and sunset might make you more likely to catch your prey/avoid your predator, and therefore your likelihood of survival.

Andy is researching a cave-dwelling fish from Mexico, that has been isolated in caves for more than a million years, with no access to sunlight, and no knowledge of "time of day". Have these cavefish kept a body clock, which would be redundant in their natural environment?

One unusual advantage of these Mexican cavefish is in the surrounding rivers another surface-dwelling river fish can be found, which do see daylight. These sighted river fish have the same ancestor as the cave fish (before they went into the caves) so make a vital comparison.

A blind Mexican cavefish next to two river fish. They have the same common ancestor and apart from a lack of eyes and skin colour are still remarkably similar so can be used to study evolution. Credit to Richard Borowsky
A lot of Andy's research has looked at gene expression. To convey what this means he used an excellent analogy. If we think of DNA as book, and genes as words, gene expression is like speaking the words aloud.

Andy's results from the cavefish show that when put on an artificial day in the lab aquaria with light and dark cycles, their genes act like the river fish, with a body clock. However, when in constant darkness, like in the cave, they lose their rhythmicity, they are not using their clock. His conclusions so far suggest that despite cavefish keeping their clock, in their normal environment the clock is not active.

Questions from the audience asked whether there were any animals that were found in the wild kept in constant lightness. Andy had mentioned that at the poles animals might be exposed to constant light for certain periods of the year, but not throughout the year. Andy theorized that it might be possible on another planet, and that would be interesting to look at.

I look forward to seeing some of Andy's work on blind cavefish published. It looks like I have a tough act to follow for my talk on "Shedding light on Body Clocks and the Brain" on 23rd March.

Saturday, 21 January 2012

UCL researchers are mapping our happiness across the week

This week I went to the first of this term's UCL Bitesize lunchtime lectures, where early career researchers at UCL talk about their work. I particularly enjoyed the second talk by George MacKerron, inventor of the mappiness iPhone app. His research question is to understand how the environment influences our happiness (green fields vs city skyscrapers), but I was especially delighted when he also showed how his data is beginning to say when we are most happy.

The mappiness app can be downloaded for free for iPhone users from the app store

My previous post was about how researchers are using twitter to determine when we are happy - MacKerron's app goes one step further to answer when and where are we happy. Subscribers get random beeps throughout the day asking them about the feelings on a sliding scale, how happy/relaxed/awake they are. They also put in a small bit of info on their current activities. The GPS on the phone can tell the researchers where they are.

His app has some of the same limitations as using twitter: people have to have access to the internet at the specific time, so grumpy tube passengers at rush hour in London are not having their feelings aired. Also, he is only sampling iPhone users, who might already be happier than the rest of us (Declaration of Interest - I'm an android user myself).

However, his app does overcome some of the limitations of using twitter feeds. App users are not publicly publishing their opinions, so there is potential they will be more honest. They are also being asked specific questions at random times throughout the day when they are happy, whereas twitter users might only be able to tweet at certain times.

MacKerran has had a great success in collecting a vast amount of data using this app. His original goal was to get around 300 participants, but with a great app and a bit of media coverage he is now collecting data from over 40,000 participants.

So what results has he been able to crunch out of this enormous data set? Apparently, Monday isn't the worse day of the week, we are on average fractionally more miserable on a Tuesday. So all the hype about Blue Monday last week being the most miserable day of the year turns out to be just hype. There are plenty of other more miserable Mondays, and Tuesdays, in the year.

Mappiness shows that Blue Monday isn't as bad as it's hyped up to be. Link here

Like the twitter studies, MacKerran's results show we are happier on the weekends. However, conversely with the twitter study, his results show that we start the day a bit grumpy and trend towards getting happier as the day goes on (data not yet published). The difference in results could be down to a number of things, including the type of app users, and that the app is limited to UK users.

I really enjoyed MacKerran's talk and I'm looking forward to seeing his work published. It's great to see how technology can increase our understanding of body clocks, and it would be good to see more apps (for android users too) developed for this.

I would recommend the Bitesize lectures if you are in London on a Friday lunchtime wondering what there is to do for free. This term's schedule is here. Of particular note there will be two talks on body clocks, this Friday Andrew Beale is talking about blind cave fish, and later on in March 23rd I will be giving my first public lecture on using light to effect your body clock.