August 2013 – The Brain Bank North West

Hating greens and “taster” genes: the bitter truth

June 22, 2015August 25, 2013 by The Brain Bank North West

You’d be hard pushed nowadays to find anyone unaware of the “five-a-day” rule surrounding fruit and vegetables in our diets. Green vegetables, in particular, are associated with numerous health benefits, such as reduced risk of coronary heart disease.¹ Yet consuming enough of these foods on a daily basis can be hard, especially if you find greens like Brussels sprouts unpleasantly bitter. But why do some of us find these vegetables less palatable? And can anything help make sprouts more appetising? Scientists in the fields of genetics and food science (or bromatology) are working to find the answers.

We all carry a unique set of instructions within our genes, defining who and what we are. Our genes encode the protein building blocks that form our bodies, including protein receptors (or sensors) within our taste buds. These receptors interact with food passing through our mouths telling us how bitter, salty, sweet, sour or umami it tastes. A special group of genetically determined receptors, known as the TAS2R group, detect bitter tastes, meaning that our genes play a key role in determining how bitter our food tastes.

The genetics behind bitterness is complex, but scientists have established a common test to explain why some people experience certain foods as being more bitter than others. This test involves the TAS2R38 bitter taste receptors and two substances they detect, phenylthiocarbamine (PTC) and 6-n-propylthiouracil (PROP). In general, the functionality of a person’s TAS2R38 receptors determines to what degree they taste PTC or PROP as bitter, with people being divided into three groups: non-tasters with non-functional TAS2R38 receptors (PTC and PROP do not taste bitter), medium tasters (PTC and PROP taste slightly bitter) and “super tasters” (PTC and PROP taste very bitter).^2,3 But what does this have to do with green vegetables?

In 2006, a lab group from Yale and Connecticut Universities set out to investigate PROP as a marker for bitterness in green vegetables (Brussels sprouts, kale and asparagus) and whether this related to peoples’ intake and preference. 110 individuals were asked to rate these vegetables, along with PROP, for bitterness and likability whilst also being asked to complete a questionnaire regarding their daily diet.

Interestingly, the results showed that people who tasted PROP as most bitter (i.e. super tasters) also found the green vegetables very bitter, inferring PROP could be a marker of bitterness for this food group as well and suggesting TAS2R38 receptors may be involved in green vegetables’ bitterness.² These people also tended to dislike greens more and eat less of them, suggesting a strong (and logical) relationship between a food’s bitterness and a lack of it in one’s diet. Thus, it seems for super tasters our genetic predisposition to produce functional TAS2R38 receptors may be working against us getting our five a day; making us find green vegetables bitter and unpalatable.

But all is not lost! Food scientists are now working on a solution to the super taster’s quandary. Mastaneh Sharafi and colleagues from the Allied Health Sciences Department at Connecticut University recently investigated the use of additives (aspartame, sodium chloride and sodium acetate) in a pilot study aimed at reducing or ‘masking’ green vegetables’ bitterness. Sharafi began by grouping 37 participants into non-, medium and super taster groups using PROP. They were then asked to rate plain and bitter green vegetables (asparagus, Brussel sprouts and kale), served together with one of the above masking agents, for likability.

To the researchers surprise, it seemed the masking agent’s effectiveness differed depending on both the vegetable and whether participants were non-, medium or super tasters. For super tasters, for instance, the two salt solutions reduced bitterness in asparagus but not sprouts or kale. Aspartame decreased bitterness across all the vegetables for super and medium tasters but had no effect for non-tasters. Participants with a significant dislike of greens and subsequent lack of these in their diets, reported improved likability with aspartame, suggesting masking agents could be useful to increasing green vegetable intake in disinclined individuals.³

So, it appears green veg haters can take some comfort in knowing that their dislike of sprouts is more likely due to their genetics than a desire to be difficult at dinnertime. And that masking these unpleasantly bitter tastes may hold the key to a palatable and balanced diet. Shafari’s small, yet noteworthy experiment certainly shows good prospects for aspartame and salt-based masking additives, but further work is still needed before us super tasters can comfortably achieve our “five-a-day”.

Post by: Megan Barrett

Megan is currently working as an associate writer at a medical communication company. You can follow her on Twitter @Meg_an12.

Drewnowski A, Gomez-Carneros C. 2000. Bitter taste, phytonutrients, and the consumer: a review. Am J Clin Nutr. 72(6): 1424-35. http://www.ncbi.nlm.nih.gov/pubmed/11101467
Dinehart M, Hayes J, Bartoshuk L, et al. 2006. Bitter taste markers explain variability in vegetable sweetness, bitterness, and intake. Physiol Behav. 87(2): 304-13. http://www.ncbi.nlm.nih.gov/pubmed/16368118
Sharafi M, Hayes J, Duffy V. 2013. Masking vegetable bitterness to improve palatability depends on vegetable type and taste phenotype. Chem. Percept. 6:8-19. http://link.springer.com/10.1007/s12078-012-9137-5

Excellent scientists that you probably haven’t heard of

August 18, 2013August 18, 2013 by lpwalker

There are some scientists that everyone has heard of; Darwin, Newton and Curie all spring to mind. Of course, their scientific discoveries were all legendary. But what about the people who have contributed just as much to the world of science but who maybe aren’t so famous? Here I’ve compiled a small list of some of the scientists I think have contributed just as much to our understanding of the modern world as those mentioned above. Although many of these people have been recognised in their fields and some have even won Nobel Prizes, their names have never entered the wider public consciousness.

1. Rosalind Franklin (1920 – 1958) and Maurice Wilkins (1916 – 2004)

The Structure of DNA. http://commons.wikimedia.org/wiki/File:DNA_Helix_CPK.jpg

Whilst Franklin and Wilkins are probably the best-known names on this list, they are not as well-known as they should be. The discovery that DNA is a double helix is now forever associated with (James) Watson and (Francis) Crick. However, there were other names involved in this remarkable achievement, including Wilkins and Franklin who were working at King’s College London at the time of the discovery. Maurice Wilkins even shared the 1962 Nobel Prize with Watson and Crick, yet somehow his name has been lost from the public consciousness. His student was Rosalind Franklin, whose work with X-Ray diffraction was the key to confirming that DNA is indeed a double helix. Much has been made of Franklin not winning the Nobel Prize along with Watson, Crick and Wilkins. But, the sad fact is that the Nobel Prize is not awarded posthumously and by the time the discovery received this honourable recognition she had sadly passed away – at the tragically young age of 37. However, what I believe to be even more scandalous, is that her contribution seems to have been entirely overlooked until a few years ago when the deserved recognition began to flow in.

As for Wilkins, Watson himself states in his autobiography ‘The Double Helix’: “I proceeded to forget about Maurice, but not his DNA photograph”¹. There is no doubt that the work done by Wilkins and Franklin was instrumental in aiding Crick and Watson with their ground-breaking discovery and their names certainly deserve to be remembered!

2. George Gey (1899 – 1970)

Stained for lysosomes (green) and DNA (blue). Photo credit: Louise Walker, 2011. (This is from the very beginning of my PhD. Which is why is rubbish. Well, I'm not going to use a thesis-quality one, am I?) — HeLa Cells. Stained for lysosomes (green) and DNA (blue). Photo credit: Louise Walker, 2011.

Although he is a figure of some controversy, I think George Gey (pronounced “guy”) deserves to be on this list. Gey was the first person to propagate the HeLa cell line – the first human cells to be successfully grown in a laboratory environment. Since then, scientists have used HeLa cells, and other cell lines created since, to make many important breakthroughs, including the discovery of a treatment for polio. And they are still used in thousands of labs across the world, including mine (see picture).

The controversy surrounding Gey² is the fact that the HeLa cells were taken from a cervical cancer patient, Henrietta Lacks, without her permission. Gey did not ask Henrietta or her family for permission to use or distribute the cells. The cell line was later patented and has made those who patented it (incidentally, not Gey or his family) very rich. Henrietta’s family received no money for the use of her cells, and until recently, Henrietta’s contribution went unacknowledged. George Gey however, did not have such financial motives; once he managed to successfully grow the HeLa cells, he gave them away to fellow scientists.

Whilst controversy remains as to how much money the Lacks family should be entitled to, I like to remember George Gey; the man who started it all out of altruism with no financial motives, a quality that should be admired.

3. Sir Edwin Southern (1938 – )

Showing the protein Tsg101 after elution from a gel filtration column, if you're really that interested. Credit: Louise Walker, 2011 — A Western Blot. Showing the protein Tsg101 after elution from a gel filtration column, if you’re really that interested.
Credit: Louise Walker, 2011

Here’s one for fellow biochemists. Edwin Southern is a British molecular biologist and inventor of the Southern blot. This is a method for detection of DNA, now commonly used in DNA fingerprinting and genetic profiling. The Southern blot was later developed into the cleverly-named Northern Blot – modified to detect the other form of genetic material, RNA. Even better, the development of the Southern Blot finally led to development of the Western Blot – a method used to detect proteins. These methods are probably used by every biochemistry lab across the world, including mine (see picture).

The Southern blot and its offshoots have become staple practices in the lab and have made way for many important discoveries. Yet I know few biochemists who have even heard of Edwin Southern or his contributions to the scientific methods they use on a daily basis.

4. Dorothy Crowfoot Hodgkin (1910 – 1994)

The Crystal Structure of Insulin Credit: http://commons.wikimedia.org/wiki/File:Insulin.jpg

Another British scientist, Dorothy Hodgkin, won the Nobel Prize in Chemistry in 1964 for discovering the structure of vitamin B12. She was a pioneer in the field of X-Ray crystallography, working on solving the crystal structure of proteins. Her knowledge was instrumental in the discovery of the structure of several proteins, but arguably her greatest achievement was in leading the team that solved the structure of insulin. This discovery led to the development of synthetic insulin – now widely used to treat people with type I diabetes.

Hodgkin has been recognised for her work in the scientific community. Along with the Nobel Prize she was also the first woman to win the prestigious Copley Medal. Some of her fellow recipients include Charles Darwin and Stephen Hawking. She was a true pioneer, not just for women in science but also for promoting peace and aid for developing countries. (According to her Wikipedia page, she did teach Margaret Thatcher, but I guess nobody’s perfect.)

While you could argue that most of these names are well-known in scientific circles, they have not become household names along with the likes of Darwin and Hawking. And this is by no measure an exhaustive list!

Perhaps one of the most endearing qualities of great scientists is that they rarely do what they do for fame or fortune. In fact, many actively shy away from the limelight. People like George Gey and Dorothy Hodgkin were certainly more interested in curing disease and adding to our understanding of the world than earning money or becoming famous. So this is just my way of thanking them for their tireless work and recognising the contributions they have made to modern science.

Post by: Louise Walker

¹ The Double Helix by James Watson, Simon and Schuster, first published 1968

²To find out more about Henrietta Lacks and George Gey, see The Immortal Life of Henrietta Lacks by Rebecca Skloot, Pan MacMillan, 2011

Attacked by your own hand: when the brain acts against you

August 13, 2013August 12, 2013 by The Brain Bank North West

Sometimes it might feel like your brain acts against your own interests. Who hasn’t regretted that extra pint or an unaffordable shopping spree? But what if your brain was controlling a part of your body against your will?

This is a relatively rare but mind-boggling condition called alien hand syndrome, where patients have the sensation of a limb acting without their control. It can feel like their arm is disobedient, and has “a will of its own”. The condition appears in the 1964 film Dr Strangelove, where the eponymous character is shown to have the condition. Medically, it was first documbetween the two hemispheres of the brain (the corpus callosum) cut. ented in patients who had undergone surgery to treat epilepsy, though it can occur after other types of brain surgery, stroke, brain tumours, infections or certain degenerative brain diseases. It is best understood in patients with epilepsy who have had the connection Following this surgery patients are generally able to continue their lives as normal, but in some cases the effects can be dramatic.

Patients with alien hand syndrome report that following the surgery one arm (and sometimes leg) feels like someone else’s, and describe the arm’s behaviour as not their own. Some patients may even be unaware of the actions of their hand. One patient who suffered a severe case of alien hand syndrome and appeared in the 2011 BBC documentary “The Brain: a Secret History”, described how her “alien” left hand would take things out of her handbag without her knowledge, or stub out a cigarette that her right hand had just lit. In cases where the “alien” hand performs goal-directed behaviours such as these, it may perform actions directly opposed to the unaffected hand, leaving the hands apparently bickering. For instance, while the unaffected hand tries to pick up a mug, the other moves it away. Conversely, the affected hand may involuntarily mirror the actions of the other hand. For these patients, when instructed to perform an action with the unaffected hand, they may be unable to do so without the affected hand attempting the same movement. In another case, reminiscent of a horror film plotline, following serious heart surgery, a patient found that her left hand was no longer under her control, and would even try to choke her. Frighteningly she had to physically restrain it with her right hand to avoid injury.

So what is going on in the brain to allow this to happen? Brain imaging research has found that alien hand movements, like normal hand movements, are accompanied by activity in the primary motor cortex (a part of the brain critical to producing movements). But this occurs without the usual preceding activity in the premotor cortex (another part of the brain involved in planning and producing motor actions), and other regions involved in planning behaviours. In patients who have had the connection between the hemispheres cut, it is possible that interhemispheric premotor to motor cortex activity is disrupted. So, in effect, the motor cortex is acting without the usual sequence of brain activity that controls it and gives us a sense of the action being one we’ve chosen to do. In addition, in the healthy brain, motor actions are accompanied by a signal to the sensory parts of the brain that will experience it (an efferent signal; see an earlier post on this blog about how this stops us from being able to tickle ourselves here). If this efferent signal is absent or faulty, your own actions may feel like someone else’s.

brain

Although it is still not fully understood what changes in the brain lead to alien hand syndrome, it seems possible that a combination of these disturbances in the brain may contribute to the sensation of the hand being autonomous. This condition has fascinated scientists for many years, and raises interesting questions about how we experience physical sensations.

Post by: Claire Scofield

Controlling the brain with light: Where are we at with optogenetics?

August 16, 2013August 5, 2013 by The Brain Bank North West

Optogenetics has had a blockbuster billing. This remarkable neuroscience tool has been lauded to have the potential to illuminate the inner workings of the brain and allow us to understand and treat neurological diseases. But how far off are we from these goals and what have we achieved thus far?

Optogenetics has been explained before on this blog and elsewhere and is explained excellently in the video below.

[youtube=http://www.youtube.com/watch?v=I64X7vHSHOE]

Briefly, in order to understand the way the brain works we need to be able to investigate how circuits of cells communicate with each other. Previously, we have used electrodes to record what is going on inside the brain. By presenting a stimulus and recording the brain’s response, we can try and interpret what this response means. The true test of our understanding, however, relies on us being able to produce the required behavioural response by stimulating the brain.

Using electrodes, we can record the response of a nerve cell when a mouse wants to turn right. Then we can replay this response back to the mouse’s brain and see whether he turns right. The problem with this is that we will not only stimulate the nerve cells we want, but all of their neighbours as well. The brain is precisely organised and neighbouring cells may carry out completely different roles so this will commonly be a large interference.

What optogenetics allows us to do is insert a light-sensitive ion channel into the cells that we want to activate. This channel will open when we flash a burst of light onto it, in turn activating our cell. This technology thus allows us look at the actions of specific population of cells without the interference that comes with using electrodes.

From http://neurobyn.blogspot.se/2011/01/controlling-brain-with-lasers.html

So in just over a decade since optogenetics was first described, what have we managed to do? I’ve split my summary into two main headings. The first highlights basic research that increases our understanding of the brain. The second, the possibilities for understanding and treating disease.

Basic research

Top row shows the behavioural set-up. Mice detect whether the pole is in the right (right) or wrong (left) position and are trained to either lick (right) to receive a water reward or not lick (left). Bottom row shows the optogenetic intervention. When a laser beam is crossed (red dot), the cortex is stimulated. Mice were fooled into licking in the left condition, even though their whisker hadn’t touched a pole. From O’Connor et al. (2013).

Optogenetics has been used successfully to understand more about perception and the senses. Karel Svoboda’s group at the Janelia Farm Research Campus in the US have been able to create what they call ‘illusory touch’ in the brain of awake, behaving mice. Mice were trained to detect the position of a vertical pole, presented near to their whiskers. When the mice sensed that the pole was in the right position, they were trained to expect a drink of water and would lick (see left). When the pole was in a wrong position, they were trained to do nothing. Once trained, mice were able to give the correct response 75% of the time.

The researchers suspected they knew the area of the brain that was telling the mouse when their whiskers touched the pole, a part of the cerebral cortex. To test this, they injected an optogenetic channel into this area and replaced the pole with a laser beam and detector. The detector was linked to a light on the skull so that when the whisker passed through the laser light beam, a signal was sent to shine light onto the cerebral cortex and activate the specific cells they were interested in. They found that by activating the cortex when the whisker passed through the beam, the mouse would lick even though the whisker hadn’t touched a pole. They had created an illusion in the mouse’s brain that his whisker had touched a pole!

Another optogenetics study that hit the headlines recently looked into memory formation in the hippocampus. Susumu Tonegawa and his team from the RIKEN-MIT Center for Neural Circuit Genetics in the USA were interested in proving the crucial role of the hippocampus in memory formation. They inserted optogenetic channels into the hippocampus of mice in such a way that when new memories were formed, the cells that were connected by this memory would also contain these light-sensitive channels.

By placing mice in an arena and allowing them to explore, the mice would form spatial memories of the arena within their hippocampus. The new cells and connections generated would form a circuit that could be stimulated with light. The next day, the researchers placed the mice in a new arena that the mouse had no knowledge of. The researchers shone a light on the head of the mouse to activate the cells formed the previous day. They simultaneously gave the mouse an electric shock. Now, when placed back in the first arena, the mouse froze. It had associated the memory of the first arena with an electric shock, even though the mouse had never been shocked in the first arena! The researchers described this as creating a false memory within the brain.

Treating disease

Perhaps the most exciting aspect of optogenetics is its potential to treat disease, with the fantastic Karl Deisseroth leading the way. Arguably, the most natural place to start when talking about the therapeutic options of light-responsive channels is with blindness.

A collaborative group led by Botond Roska at the Friedrich Miescher Institute for Biomedical Research in Switzerland has looked into retinitis pigmentosa, a form of blindness caused by degeneration of the retina at the back of the eye. Using two animal models, they have been able to restore vision by inserting a light-sensitive channel into the retina. This therapy worked well enough to allow the previously blind mice to be able to carry out visually guided behaviours.

A further use of therapeutic optogenetics has been mooted for the treatment of Parkinson’s disease. In Parkinson’s, a region of the brain called the basal ganglia degenerates, leading to an inability of the patient to co-ordinate movement. Increasing the activity of this region has been shown to have therapeutic benefit and the lab of Anatol Kreitzer at the University of California, US have shown potential in an optogenetic approach. They were able to mould the activity of the basal ganglia in such a way to create Parkinsonian-like symptoms in mice and also to reduce Parkinsonian-like symptoms in a mouse model of Parkinson’s.

So has optogenetics lived up to the hype so far? Well despite its application in humans lacking somewhat at this point, it appears that optogenetics has already answered some vital questions we have. The challenge now is to develop the technology further so that we have more accurate and controllable tools for when we’d like to start using them in humans. The excitement surrounding optogenetics is still widespread and there is no evidence yet that the bubble is set to burst anytime soon.

Post by: Oliver Freeman @ojfreeman

Papers Referenced:

Sensory Perception – O’Connor et al. Nature Neuroscience (2013)

Memory Formation – Ramirez et al. Science (2013)

Blindness – Busskamp et al. Science (2010)

Parkinson’s Disease – Kravitz et al. Nature (2010)