Category Archives: Biology

What’s going on in the Biology field

What Are Stem Cells? (PART I)

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Stem cells have been an important part of medicine since their isolation from mice in 1981, but in actual fact they have been used far longer than this. Bone marrow transplants for leukaemia and skin grafts for burn victims both rely on the principles of stem cells and regeneration. Even in ancient Greece they were imagined as an essential part of human biology, shown by the story of Prometheus who, as punishment for stealing Zeus’ fire and giving it to man, was bound to a rock and had his liver pecked out by a giant eagle every single day, just to have it grow back each night. Nice.

The term stem cell actually covers different types of cells, and is arguably thrown around a little too often nowadays. They can divide forever and generate new cell types, much like an oak tree can keep on growing, throwing out new branches. This power has made them exciting with respect to repairing damaged organs and for use in developing new drugs.

Embryonic stem cells are defined as being pluripotent, that is to say that if you took one embryonic stem cell it has the capacity to become any other cell type of the human body. These are the roots and trunk of the oak tree, shooting branches off in any direction it needs, whilst each root can make a new oak tree. During gestation, these are the cells that build us; the fertilized egg generates a shell in which the embryonic stem cells grow, they then divide and follow paths to different fates, for example a neuron, or a heart cell. This ability allows one original cell to go on to produce all the cells that we are made of. The same principle applies for all life; we all start off from the same building blocks.

Adult stem cells are pretty much what it says on the tin. They are stem cells that continue to stay in the body even into adulthood. Adult stem cells are the branches of the great oak; they do not under normal conditions make a new tree, but continually sprout new leaves and acorns necessary for the ongoing life of the original oak. They are found in brain, bone marrow, blood vessels, muscle, skin, teeth, heart, gut, liver, ovaries and testicles. The main difference between these cells and embryonic stem cells is their ability to make new cell types. Essentially, adult stem cells are restricted in what cell type they can make, only creating cells down a certain path, for example the neural path. The body does not want teeth filling our arteries, nor intestines sprouting out the top of our head, so cell types are kept limited.

Induced pluripotent cells – or IPS cells for short – are slightly different matter. They are the acorns and cuttings which when replanted can generate a new oak tree. Scientists have found that they can take cells from our skin; force expression of a combination of genes and this reverses the path the cell has taken, reverting it back to a pluripotent stem cell i.e. a cell that can then generate any other cell type. This demonstrates an incredible progress in our understanding of stem cells.

In the next two parts I will give a slightly more detailed introduction to why and how stem cells are used, and the major points of controversy that arise. Hopefully, it will give an insight into the lives of scientists that work on them and help you decide your attitude towards the subject.


Stem Cell Oak Tree – I.S.

∞

Finding out what makes you, you.

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Although Genetics is often seen as just another jigsaw piece making up the wide subject of Biology, it really underlies the whole study.

After all, is the most fundamental question of life not how does the set of chemicals inside us provide our every essence? How are those chemicals changed from simple molecules to everything that makes up a human being?

One thing which makes Genetics so interesting is that not even the best geneticists in the world can fully answer these questions. It is still a science very much in its infancy and early stages of understanding. After all, it was only around sixty years ago that James Watson and Francis Crick made the discovery of the structure of the DNA double helix. What is most fascinating about how these men made their discovery is that they came to their final theory of the double helix without any experiments of their own; they simply brought together other people’s evidence and used it to their advantage to gain their own final answer.

The less molecular side of Genetics which most people have heard something of is that of Gregor Mendel’s pea plant experiments: he performed genetic crosses with the plants, noting parent and offspring characteristics. As far back as 1856, he laid the foundations of what remain the basic principles of Genetics in these modern times. Mendel introduced the theory of recessive and dominant characteristics, without fully understanding what he was proposing.

A gene, in simplified terms, is a stretch of DNA coding for a characteristic in an organism. Allele is the word used when there are two or more different forms of a gene, so there can be different alleles for a particular gene. These different alleles can be classed as recessive or dominant, which basically do as their names suggest i.e. genes come in stronger or weaker forms; dominant being stronger and recessive being weaker. This means that one allele can dominate over the other and if both alleles occur, the so-called dominant allele will be shown. Since we have two copies of every gene, one from our mother and one from our father, any allele combination can occur. Therefore for a gene with two alleles, A (dominant) and a (recessive), there are three different allele couplets which could occur: AA, Aa or aa. This is called the organism’s genotype, the genes contained within its cells. The organism’s genotype produces a particular phenotype, which is the characteristic shown by an organism due to its genotype. For instance, in Mendel’s pea plant experiment, he found that yellow colour is dominant to green colour in the peas – yellow colour could be shown by the allele Y and green colour can be shown by the allele y. This means that in this case, the pea plant can have the genotypes of YY or Yy which will show a yellow phenotype, or yy which will show a green phenotype.

Grabbing attention

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There are certain things in the environment that grab our attention – loud noises, flashes of light and rapidly moving objects.

These are all reasons why we are likely to spot ambulances dashing towards us and mean that we can act in time to get out of the way.

However, there are also more subtle things that attract attention when we are surrounded by a more mundane environment.

Certain properties of the world are more SALIENT to our visual system than others.

These are: changes in colour (e.g. red to green); changes in contrast (e.g. sharp to blurred ); changes in intensity (e.g. bright to dim); changes in orientation (e.g. vertical to horizontal).

These are some of the reasons why human EYES are so effective in capturing attention – the iris is coloured, there is a sharp contrast between the pupil, iris and sclera and there is a change in orientation of the contrast boundaries around the eye.

In our environment there are often many other things that share these features that compete for our attention e.g. traffic signs, advertisements, bright clothing. As we look around some of the things we look at are influenced by this change in VISUAL SALIENCY.


When we look at pictures, we can break them down into their constituent properties. Below are two photograph and their associated VISUAL SALIENCY maps.

These maps can predict where you will look in a scene on the basis of visual saliency. The little “1″ on the maps above show the most salient point. The following 9 most salient points can be found by following the red line around the photos.

The model doesn’t get it exactly right as we are able to over-power these properties and CHOOSE to look where we want but when we first see pictures we are more likely to look at the salient regions, before we’ve got the gist of what is going on.



At Sheffield, we’ve recently published a paper which investigates whether people with autism and Aspergers look at scenes in the same way.

In the journal Neuropsychologia, we have shown that people with autism also show this bias for looking at salient regions when they first see scenes (Freeth, Foulsham & Chapman, 2011).

However, we also showed that both typically developing viewers and viewers with autism and Aspergers are more strongly drawn to looking at social aspects of scenes – the people – even when they are not “visually salient”.

This finding is very surprising as it was previously thought that people with autism wouldn’t be drawn to look at people.

However, there was also an important difference: participants with autism/Aspergers were significantly slower to look at people’s head and faces when they were looking at scenes than the typically developing participants.

It seems that the fast-track mechanism to attend to other people is absent in people who have autism/Aspergers.

Neurological disorders and science funding: a plea.

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Being a lowly PhD student and thus spending most of my work-time focusing on a very narrow research programme, I actually know embarrassingly little about the wider field in which my work sits.  This is something that to some extent, I accept as inevitable for now, though it is something I very much hope will change over time as I get more chances to meet and talk with people from different areas of research, and maybe in the future be involved with multiple research projects.
At the moment, I have something particular in mind and that is the broad and complex area of neurological disorders and neurodegenerative disease.  Wikipedia returns a terrifyingly long list of these.  Of course, many people are familiar with some of these afflictions and their effects, such as Alzheimer’s disease.  Then there are those which many people have heard of, but common misconceptions abound as to their symptoms and progression, such as schizophrenia, which, contrary to popular belief, is neither classified by nor typically includes ‘multiple personalities.’   
But far fewer people may be familar with Fatal Familial Insomnia, an extremely rare inherited disease in which sufferers literally lose the ability to sleep, along with experiencing hallucinations, panic attacks and dementia.  Death eventually follows, usually within three years of diagnosis, and there is currently no cure.
The problems resulting from neurological disease are however, broader than the direct symptoms the disease may cause.  In Williams’ syndrome, for example, a chromosomal disorder, sufferers show (amongst many other things) extreme sociability.  This is possibly due to the disorder’s effects on the amygdala, a subcortical brain structure important in regulating our fear response.  While this may at first not seem to be problematic, our wariness and mistrust of strangers is an important behavioural tool in helping to ensure our safety, and its disordered function – as in Williams’ syndrome – can put sufferers in real danger.
There is a good reason for my broaching this saddening subject, and that is the government.  With just days to go before the Tory-Lib Dem coalition unveil their plans for making £83billion worth of cuts, there is growing concern that science funding will be disproportionately hit.  Beyond my common sense, I cannot speak for other areas of science and why reducing their funding will be disastrous.  Nor am I going to claim to be an expert about the other effects of these cuts,  such as the oft-cited inevitable ‘brain drain’ that will ensue or the ultimate detriment to the economy that I believe science cuts will cause.
One thing I do know about, though, is a set of nuclei called the basal ganglia.  I’ve mentioned them before in this blog and the Inside TRAK blog.  They sit in the middle of the brain, beneath the cortex.  They’re common to all vertebrates, and while their functions are many and varied, our research group believes their primary role is that of ‘action selection’, or choosing what to do next. We think their other functions enhance or complement their ability to do this.  They rely heavily on a ‘neuromodulator’ called

dopamine.  This is often referred to in the press as a ‘pleasure chemical’ but the reality is that its roles, too, are many and varied, dependent on the brain region in question, and not entirely understood.  We do know, however, that it is required for the basal ganglia to do their job properly.  They are constantly ‘bathed’ in dopamine, which is synthesised in a region called the ‘substantia nigra’ or ‘black substance’, so called because is literally appears black in brain slices.
The degeneration of this area is Parkinson’s disease.  It causes the amount of dopamine supplied to the basal ganglia to diminish, and the effects are profound and debilitating.  An inability to initiate desired movement and tremor are the most commonly known symptoms, but sufferers can also experience depression, hallucinations, anxiety, dementia and obsessive-compulsive behaviours.  Now it just so happens that at least some symptoms of Parkinson’s disease can actually be managed rather well, at least for a few years.  Some interventions, such as Deep Brain Stimulation, can provide really quite radical improvements.  This is fantastic, but our understanding of exactly why this method works is far from complete.  If we can continue to research the mechanisms by which it affects the disease, it may be that this can be applied to far more disorders.  It has already been shown to improve chronic pain and even depression in some cases.
However, the picture is not always so clear.  The basal ganglia are also implicated in schizophrenia, obsessive-compulsive disorder, Tourette’s syndrome and many others.  The awful and incurable Huntington’s disease also primarily affects the basal ganglia.  Many of these conditions are not nearly so well understood, nor is their treatment always so effective.  Subsequently, quality of life for sufferers falls drastically; levels of depression and even suicide can be very high.  Our level of understanding about these afflictions, and our ability to prevent or treat them is hugely dependent on the money that is invested into their research. That research is vital if we are to continue making progress like this from the lab in which I work towards improving the treatment, prognosis and quality of life for sufferers, and the prevention of such disease in high-risk groups.  If we don’t research these diseases, we can’t understand them, and if we can’t understand them, we can’t help.  I think this is hugely important work, and I hope that you will agree with me.  If so, it’s not too late to do a little something about it. Please go to the Science Is Vital website, and sign the petition against cuts to science funding. If you can, email your MP about it, too, and ask them to sign EDM 767.  Please spread the word and help UK science continue its vital research.

Analysing Brainwaves

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Everything we see, hear and touch is processed by our brains. Every time we experience something the neurons in our brains start to fire and emit little pulses of electrical activity. All of these millions of tiny neurons fire in a systematic way in big chains of networks. Different parts of networks communicate with each other so that we can interpret all of the complex stimuli that are entering our senses every second.

Of course, everyone’s brain interprets the world in a slightly different way but there are also many similarities. Understanding the processes that go on in the brain and how the networks of neurons work can help us to understand and predict behaviour.




One way of working out how all of these processes work is to measure brain activity by recording the electrical signals produced when neurons fire – when we are thinking. This can be done using electroencephalography (EEG) equipment. This technique involves wearing a big net of recording devices that measure the electrical activity that is going on in your brain. In Sheffield, we have state of the art equipment which contains 128 extremely sensitive recording channels. This technique is absolutely fantastic for working out the exact timing of the processes that go on in the brain. Recordings are typically taken 250 times each second. Now, just imagine how much data you get from 128 recording sites taking readings 250 times each second – phew! Thankfully, we have computer programs to process this data but even with our really powerful computers, some types of analyses may need to be run overnight.


Here are some examples of what electrical activity in the brain can look like. Certain things we do produce very distinctive signals. A big peak is usually produced by blinking. We can also usually see swallows or other small movements in the EEG signal.

 

We can also tell how alert someone is. If someone is nearly falling asleep they start producing a lot of alpha frequency signal (about 10Hz) which produces a very distinctive signal. If this happens, we know we’ve produced a very boring experiment!


The EEG studies that we are running at the moment mainly investigate different aspects of attention. We are looking at the brain’s very early response to seeing a new stimulus. We can see changes in brainwaves as soon as 0.1 seconds after things appear, if not before. We are also trying to understand how the brain puts together information about different features, such as colour and shape.


Here is an example of some data we recorded from one of our volunteers.

This is the average waveform produced from hundreds of trials recorded from site 62.

Below are scalp maps showing different time points in the trials

 


We are always looking for volunteers to participate in our studies to try to understand more about how the brain works. If you are interested in finding out more, get in touch and we’ll let you know if we have any studies suitable for you to participate in right now. The EEG lab at Sheffield is run by Dr Elizabeth Milne who also runs the Autism Research Lab. Other researchers in the lab are Dr Megan Freeth, Tom Bullock, Cigir Kalfaoglu and Mandeep Jabbal.

If you would like to participate in one of our studies, get in touch with us at the Sheffield Autism Research Lab.

When trying harder makes things worse

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 Hi, I’m Lauren! I am a second year Psychology student at the University of Sheffield and I have just completed a summer placement here.


My project title has been “When trying harder makes things worse” and I’ve been investigating what happens to skill performance when you pay attention to what you are doing or how you are doing it. I’ve been looking at to different types of attentional focus:

 ’internal focus‘ is attention directed to body movements

 ’external focus’ is attention directed to the external environment

 

Previous research on this has primarily looked at how these types of attention impact on target sports, for example football which it topical considering the recent world cup! What is interesting about my project is that unlike previous research, I have investigated the effects on touch-typing.

To test how attention focus affected typing, we asked touch-typists to type two short stories. We measured their speed and accuracy and combined them into a single measure of ‘inefficiency’ (i.e. higher scores mean worse typing performance).

The first story typed is the control condition where participants were instructed to type the story as quickly and accurately as possible. The second story is the experimental condition where different instructions were given to participants, according to whether they were assigned to the internal or external focus group. Internal focus participants were instructed to not type with their left hand’s ring finger and external focus participants were instructed to not type the letters w, s or x.

The thing to notice about these instructions is that they both result in the same behaviour – participants were essentially given different instructions to carry out the same task. This is because the left hand’s ring finger types out the letters w, s and x. So the only thing varying between the groups was the focus of their attention, not what we were asking them to do.

The results were really interesting:

**We found that telling people not to use one of their fingers caused significantly greater disruption to performance than telling people not to use certain keys – even though this meant missing out the same letters i.e. focussing attention internally (to fingers) made people significantly worse than focussing attention externally (to keys)**

This is shown in the graph below. Notice that both experimental conditions were worse than the control conditions (the specific instructions made the task harder for everyone), but our analysis shows that the internal focus was significantly more difficult again than the external focus condition. For my first ever experiment, these are great results!

My results can be used to support the ‘constrained action’ hypothesis. This hypothesis states that an attempt to consciously control our body movement disrupts functioning of motor system. This occurs by interfering with automatic control processes. Previous research coincides with my findings and this theory. My project indicates that trying harder makes things worse is observable in touch-typing and not just target sports. All in all my project was a great success and proves that you do not need to necessarily try harder at the things you are already good at!

This project was supervised by Dr Tom Stafford and Cigir Kalfaoglu.


Further reading: Logan, G. D., & Crump, M. J. (2009). The Left Hand Doesn’t Know What the Right Hand Is Doing. Psychological Science, 20(10), 1296.

 

The importance of computational neuroscience

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Before I get started, I’d just like to quickly point to a video piece we managed to get into New Scientist!  Please see here for this very exciting media coverage!

 

Now, I wanted to write a little bit about how Inside TRAK has been useful for demonstrating why computational neuroscience is important.  You can think of computational neuroscience as a field in which we are concerned with the information processing capabilities of the brain.  We aim to understand behaviour in terms of the chemical and electrical activity of different components of the central nervous system (brain and spinal cord).  This doesn’t just mean associating certain behaviours with particular regions of the brain, though this is an important part of neuroscience and often helps guide computational work.  Rather, we look at the manner in which different regions of the brain react to different types of information, where and how this information is further propagated, and we attempt to understand how the processing that we observe might be responsible for the behaviours we observe.  This can be contrasted with psychology, for example, which tends to use a more abstract level of explanation.  So, whereas a psychologist may be more concerned with explanations of behaviour in terms of constructs like attitudes and emotions, a computational neuroscientist may prefer to interpret those same behaviours in terms of the efficiency with which certain neurons propagate information in different contexts.  It is important to realise however, that these approaches are complimentary, and can help guide each other towards better and more comprehensive theories of why we behave the way we do.  

 

In computational neuroscience, sometimes we focus on the significance of the activity of individual neurons; other times on that of the average activity in larger structures composed of millions of neurons.  The latter is referred to as the ‘systems level’, and is the level with which Inside TRAK is concerned.   Comp neuro research involves creating models of these brain systems and using them to simulate the brain activity that we observe in the biological system.  This clearly requires a detailed understanding of the neural systems in question.  Using brain imaging and other techniques, experimental neuroscientists have gathered mountains of data revealing which parts of the brain are active when we perform particular tasks. Simulations that reproduce this neural activity – like the one powering Inside TRAK – help us to test theories of how our brains work.  Inside TRAK is a great example of this.  As the model that’s powering it is based on the real neural systems we know to be involved in deciding where we look, if the model can’t drive the robot to look around, we know that we’re interpreting something wrong.  Perhaps it’s just a trivial problem; perhaps our model is too high level and we haven’t modelled sufficient detail.  Alternatively, we may have completely misunderstood something about the way the system works. 

 

However, this is by no means the only reason why it’s important.  It’s not until you try to emulate a behaviour that you are forced to address the assumptions and omissions you might have made in your theory.  I like to call it the ‘magic box’ problem.  It’s all too easy for us to brush over what’s really happening in the brain by explaining behaviour in terms of things we all instinctively think we understand, but find it very hard to explain what we really mean.  If we think about this in terms of Inside TRAK, we might say that the robot weighs up the pros and cons of looking left or right, and that’s how it decides to look one way or the other.  We may feel as though we’ve explained what’s going on as ‘weigh-up-pros-and-cons’ is a very instinctive process to us.  This, however, is the ‘magic box’.  Several options are introduced to the magic box, something happens inside it, and out pops the decision.  Until we can simulate what’s happening in that box in terms of the brain though, we don’t understand what the brain is doing.   Observing the behaviour of models we have built also helps us to generate predictions about what is happening in the brain, as we can poke and prod it in ways we can’t do with biological systems.  We can systematically vary parameters that are representative of very real things in the brain, and examine the subsequent behavioural effects in order to further understand the biological systems on which our models are based.   I could go on, but this post is probably dragging as it is, so I’ll stop there and point you to an excellent essay by Joshua Epstein about why modelling is important.  It’s neither long nor boring (possibly unlike this post), so I really recommend it.  

 

Next post: a more detailed look at the function of iTRAK with some pretty pictures and everything.

 

 

2010 – The International Year of Biodiversity

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Unbeknownst to many, 2010 is the International Year of Biodiversity.  This is the year in which we as a species are meant to come together and cherish the diversity of life on this planet.  We should unify over the common aim of preventing further biodiversity loss, realise how precious biodiversity is and how costly further loss will be.

Personally I have felt that this glorious year of change has passed me by somewhat.  The Convention of Biological Diversity’s 2010 biodiversity targets, set in 2002, have not been met and pollution, overfishing and deforestation, to name a few, are as rampant as ever.  In fact in the wake of the Gulf of Mexico oil spill, 2010 may well be remembered by many as a year of environmental calamity.

Perhaps what we are really celebrating is the raising of awareness of these issues.  Our screens are filled with nature programs, politicians seem to be finally acknowledging the important of the environment and organisations such as the Wildlife Trust and the RSPB are doing their upmost to reach out to the British public. Even Edward Norton is involved (http://www.youtube.com/watch?v=IwbnElGXg2I).  As a biology student, however, there seems a distinct difference between awareness and action (woefully seen in the Copenhagen conference earlier this year).

Despite my pessimism, many people may look out of their window and see that the sun is shining, the birds are singing and plants everywhere are displaying to us in their full glory.  Even those pesky insects are still around.  What is all the fuss really about?

Although it may be difficult to see, our planet is experiencing phenomenal rates of climatic change and species extinction, spurred on, it seems, by human activity.  These events are occurring at such a rate that we are forging our own geological era, known as the Anthropocene, or human era.  But why is this important to us?  So there are a few less species, so what?

The aim of this blog is to answer some of these questions; to look at what biodiversity is and why it is important, to see how we are causing species extinctions and the impact this has, and perhaps most importantly to consider how we can stop this trend and conserve the diversity of life on this planet.  I will endeavour to show you what conservation is really about, that it consists not simply of a bunch of hippies chained to trees, but of hundreds of highly trained scientists working together to try and save the gift of biodiversity.

Art and science on radio Sheffield

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The iTRAK exhibition has been going down a storm, with a packed opening event and TRAK incidentally participating in seminars held at Access Space.

 

A more extended post will be coming shortly, but for now here’s a recording of Jon Chambers, one of the model’s developers, and Dora Militaru, the artist, talking to Kate Lindeholm from BBC radio Sheffield.

Inside_TRAK_Radio_Sheffield.mp3 (6.62 mb)