Sarah Fox

Fluorescent cats: a bright idea which may help us understand AIDS.

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Glowing kitties, more than just a novel night light!
Glowing kitties, more than just a novel night light!

An article recently published on the BBC website (link) caught my eye last week, and not just because I’m a sucker for cute kitties. It appears that researchers from the Mayo Clinic in Minnesota have developed a reliable method of transferring new (non-feline) genes into unfertilised cat eggs. Amazingly these modified egg cells, once fertilised, can go on to produce kittens which express these new genes throughout their bodies!

For this post I thought it would be interesting to give a bit more detail on this research addressing the hows and whys of these fluorescing felines.

So…why cats, why green and how can this help us understand and hopefully treat AIDS?:

Cats are not the first animals to be modified to glow under UV light, indeed some of you might remember similar articles from the late 90’s showing pictures of glowing mice. This green glow is the product of a jellyfish gene which has been artificially inserted into the animals own genome. Once this gene is established it creates a protein (Green fluorescent protein or GFP) which, when exposed to UV light, emits a green glow.

3 very different creatures glowing with GFP
Although green is the standard, fluoresent proteins exist in a number of colours. The above picture was made from colonies of living bacteria each expressing a different fluoresent protein.

Of course there is more to this research than just making animals glow! GFP is often inserted into cells along with another gene of interest, in this particular article that is a gene which provides resistance against FIV (feline immunodeficiency virus). The GFP provides a quick and easy way of finding whether or not an experiment worked, i.e. if the cells glow green they have taken in the new genes, however if they do not glow they probably have not.

The insertion of new genes throughout the body of an animal, as seen here, is not easy to achieve. In fact, this study represents the first time this method has been successfully used to genetically modify not only a cat but any carnivore. The key to its success appears to be the way researchers inserted these new genes. In brief; the genes were injected into unfertilised cat oocytes (egg cells), which were later fertilised and allowed to develop for 7 days. If after 7 days these developing embryos glowed green they were transferred to a surrogate mother, who later gave birth to the modified kitten.

The first image shows the new genes being injected into a cat oocyte. The second shows the developing embryo (at this point only a ball of cells, known as a blastocyst) glowing green. Black and white bars represent a scale of 100 micrometres (1 micrometre = 1 millionth of a metre).

The cat has been chosen as the subject of this study, in favour of other more common laboratory animals such as rats and mice, since cats are susceptible to infection by FIV. FIV is a virus similar in structure, genome and symptoms to HIV (human immunodeficiency virus), the cause of AIDS. Although HIV and FIV are not identical and cannot pass between species, their similarities are great enough that advances in our understanding of FIV will undoubtedly lead to a better understanding of HIV and possibly to new treatment strategies.

The gene researchers have inserted into these cats along with the GFP comes from the rhesus macaque (a type of old world monkey). This gene produces what is known as a restriction factor. This specific restriction factor, which is not naturally found in cats or humans, blocks early viral infection, therefore theoretically protecting the animal from viral attacks.

Viruses such as HIV and FIV are very simple structures, consisting of only a viral coat (like the skin of a balloon) and genetic material with a small number of viral proteins contained within this coat (for more detailed information on HIV and similar viruses see: here). Infections begin when a virus enters a host cell and multiplies. The restriction factor used in this study stops the virus from releasing it’s genetic material into the infected host’s cells, therefore stopping multiplication.

Both cats and humans are likely to benefit from this work.

The study so far has found that individual cells from these modified cats are resistant to the FIV virus and future work will soon establish whether this resistance can also be seen in the whole animal. This research is laying strong foundations for future work on HIV gene therapy and will undoubtedly prove beneficial for treating such viruses in both feline and human populations.

Post by: Sarah Fox

For original work see here (subscription necessary to view full article)

Your plastic brain

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As part of my undergraduate degree I spent a number of sessions studying the anatomical details of preserved human brains. I’m not sure why, but part of me naively expected there to be something awe-inspiringly beautiful about the organ which makes us who we are. Indeed, I can’t deny I was slightly disappointed when our class was presented with a small wrinkled object, dull pink in colour and with a consistency I would liken to children’s play putty. However, looking back on this experience I feel humbled by the knowledge that we are who we are because of this reasonably mundane organ.

Preserved human brain

The human brain weighs around three pounds (a similar weight to three loaves of bread) and houses as many as 100 billion brain cells (neurons). These cells form a number of intricate networks, specialised towards converting sensory information, smell, taste, touch, vision into conscious experience and action.

During our early development neurons forge set communication pathways, the course of which are specified by our genetic code. This genetic framework ensures that we all have the same basic neuronal scaffolding i.e. sensory cells of the eye contact visual areas of the brain whilst those from the ear contact auditory centres etc. (note when things go wrong: Synesthesia). This means that to a large extent we all experience the world in a similar manner. However, the numerous idiosyncrasies which make us individual are likely to depend on the brain’s ability to subtly modify the wiring in many of these networks. Therefore, although some important connections in the brain are hard wired from early childhood, others are referred to as ‘plastic’ and can change throughout life. This ‘plasticity’ underlies the brain’s ability to adapt to new situations and learn new information.

Our brains are plastic…well not literally.

The wiring patterns of cells within brain networks can be altered through three different methods:

  1. The strength of pre-existing neuronal connections may change (also known as synaptic plasticity).
  2. The way individual neurons respond when activated may alter.
  3. New connections may be formed or old ones removed.

Of the above list method 1 is the most widely studied and also happens to be the form of memory my research focuses on. This type of memory requires changes to occur at the region where two neurons connect (commonly referred to as a synapse). Therefore, to fully understand how this process works it is first necessary to appreciate how neurons communicate through these synapses.

A typical neuron can be separated into three functional segments; the dendrites, the axon and the cell body. Although the shape and size of these segments varies from cell to cell, their functions remain largely conserved. Dendrites are the neurons primary input structures, they spread out like branches (hence the name dendrite: from Greek, dendron, ‘tree’) and form synapses with axon terminals of neighbouring cells. Conversely, axons are the neurons primary output structure, transmitting messages from the neuron cell body to other local cells. The cell body, or soma, sits between these two segments supervising the resulting conversation, listening to input from the dendrites and deciding upon the best answer to send via the axon.


Neurons

As the name ‘synaptic plasticity’ indicates, the all-important structure for this form of memory is the synapse. Therefore, using the magnifying glass pictured above, we can now zoom in even further and take a look at how a single synapse on the above neuron functions.


A synapse

The synapse is where an axon terminal from one neuron meets a dendrite of another. Scientists used to think that these two structures touched, however, we now know that a small gap of around 12-20 nano meters (one nano meter is a billionth of a meter) exists between them, this gap is called the ‘synaptic cleft’. The axon terminal communicates by releasing chemicals, known as neurotransmitters, into the cleft. This chemical message crosses the gap and is detected by structures on the adjoining dendrite, thereby notifying the receiving neuron that a communication event has occurred (Note: there are many types of neurotransmitter each of which have different effect on the receiving dendrite).

Individual neurons receive a large number of synaptic connections. These synapses are not all equal, some will have a strong effect on the receiving neuron, encouraging it to send out a message of its own, whilst others will be weaker only exerting a small effect. Indeed, a number of these weak synapses may need to work together to cause the receiving cell to react in the same way as it did to input from one strong synapse. However, the strength of a synapse is not set in stone. Synapses themselves are ‘plastic’ and, given the correct circumstances, can be strengthened or weakened.

Such changes enable us to adapt to new situations, form new memories and are ultimately essential for us to lead a normal life. Hence why it is so important that we understand how and why some synaptic connections become strengthened whilst others do not. This knowledge will not only lead to a better understanding of human memory but will also help us understand what happens when things go wrong, for example during diseases such as Alzheimer’s.

Post by: Sarah Fox


Seahorse and friends: a stroll down memory lane.

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I think it’s fitting to begin my first official ‘factual’ post with a fun filled, informal yet informative, trip through my own area of research.

I study a region of the brain known as the hippocampus. This area takes its name from the Latin for seahorse (from ancient Greek: hippos, “horse” and kampos, “sea monster”). The picture below shows a human hippocampus removed from its surrounding brain structures and nicely illustrates where this name comes from:

                                (Source Professor Laszlo Seress, University of Pecs.)

Our hippocampi are located bilaterally (one on either side of the brain) nestled on the underside of the temporal lobe. The image below shows the hippocampus in blue (looking decidedly less like a seahorse) sitting within the temporal lobe, shown in red.

If you were to take the hippocampus pictured above and cut it in half you would find that the inside is not homogeneous, in fact it consists of a number of interlocking cellular semicircles arranged in a circuit (looking rather similar to a swiss roll).

Cells within these curves receive information from a number of brain regions, including visual, olfactory (smell) and auditory (hearing) systems. The cellular circuits found within the hippocampus are believed to be vital for combining such information together to form memories. Indeed, individuals who lack a functioning hippocampus often suffer from a specific inability to form new memories (anterograde amnesia), as illustrated in the films below.

At this point I have the desire to be insanely pedantic, and it’s my blog so I will be! In both these movies the characters are said to have lost their short term memory however, this is not technically correct. Although there is significant debate over the precise functions of the hippocampus, the memory loss experienced by these patients is more likely to represent an inability to transfer new experiences into a long term store rather than representing damage to a short term specific memory system. Or to be significantly less pedantic we can always just say that their swiss roll seahorse is on the frits!

Interestingly damage to the hippocampus does not interfere with all forms of memory. Indeed, individuals with hippocampal damage retain the capacity to learn new skills and often express a sense of familiarity towards recently observed objects, although without any conscious awareness of these memories. For example the, now famous, patient HM (Henry Gustav Molaison) who suffered severe damage to both his left and right hippocampi, retained the capacity to learn new skills such as mirror writing. However, whenever HM was asked to conduct a mirror writing task he argued that he was unable to do so and was always shocked upon discovering his proficiency.
Try it yourself: Print out the star pattern below and hold a small mirror next to this, now (looking only in the mirror) attempt to trace around the star remaining within the two outer lines – the task is much harder than you might think!


8 Sided Star Craft Pattern

Therefore it is believed that the hippocampus is only part of a much larger memory system. Indeed, there are a number of structures situated around the hippocampus within the medial temporal lobe which may all be crucial for different types of memory. I.e. emotional/ fear memory has been linked to the amygdala (a fun link for auditory learners out there ^_^) also object recognition may require the perirhinal cortex. However, the hippocampus is still ultimately recognised as being central to the process of linking many separate aspects of an experience together to form a full flavored memory.

My specific line of research explores how individual cells within the hippocampus form long lasting memories. This basically involves me being a ‘fly on the wall’ listening in on conversations between these cells and understanding how different external factors can influence their communication. This is important for understanding not only how and why we form certain memories but also what happens when things go wrong, for example during debilitating diseases such as Alzheimer’s.

Post by: Sarah Fox


What is science?

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Ok, so as a precursor to my first actual science post I want to provide a brief overview of how science works. I hope that this will dispel a few myths and set the scene for things to come:

Many of us leave formal education with the belief that science exists within our society as a repository for facts, a black and white discipline housing the answers too all our questions. This assumption is however not entirely true. Science is of course a human endeavour and, as such, open and welcoming to a range of theories and opinions. Indeed, science could not progress were it not obliged to provide a vibrant environment within which great minds are encouraged put forward and test their own theories. However, in order to remain focussed and make progress in this sea of ideas a theory can only be accepted following extensive testing. Indeed, even then a theory only remains accepted until otherwise proven incorrect. This means that, contrary to popular belief, science is an adaptive process with no real black and white, only consensus and the drive to constantly question and test ideas, new and old.

This results in a major problem when discussing scientific ideas with a non-scientific audience; this being how we decide when a theory has gained sufficient experimental backing to be addressed within the public sphere. Undoubtedly there are a number of amazing and marketable theories flying around in the academic ether. However, I believe that it is unethical to sell any juvenile scientific theory as fact, especially when it contradicts current scientific consensus. This does not mean that new theories should be hidden from the public, only that they should be put forward within the context of other similar research. This will allow the public to make an informed decision as to whether or not they believe the theory to be credible.

Now before I’m battered down with comments defending the underdogs of science and pointing to the countless occasions when consensus has been forced to change. I fully acknowledge that a number of the most influential scientific discoveries were at first controversial, challenging the accepted dogma and eventually providing us with a better understanding of the world around us. However, as stated by Carl Sagan ‘extraordinary claims require extraordinary evidence’. It is not enough to simply put forward a relatively believable hypothesis, this must also be thoroughly tested and should fit within the framework of knowledge within that specific area. However comfortably a puzzle piece may fit on one side, if it fails to fit on the other three, it is most likely in the wrong place!

Therefore all following scientific posts will be nestled within a framework of similar research findings to show how they findings fit within their field.

Rant over, science to follow!

Post by: Sarah Fox