Procaffinating

I don’t know about you but the first thing I do after arriving at work in the morning is grab a cup of coffee. Like many say ‘I can’t function without it’.  In the UK alone over 50 million cups are consumed in just one day!  So what exactly is it about coffee that makes us crave it so much?

Although originally native to the tropics, the coffea plant is now grown in over 70 countries around the world, producing two main types of coffee, Coffea Canephora (also known as Robusta) and Coffea Arabica.  Harvested coffea fruit (also known as cherries) are dried to reveal the beans which are then hulled and polished.  Beans are then roasted, releasing the caffeol oil (which is stored within the bean and gives them their distinct brown colour and aroma). Among other chemicals found in these beans is caffeine, the chemical responsible for the stimulatory effect of coffee. Caffeine is absorbed into the body through the small intestine, where it is then able to cross the blood-brain barrier and produce the psychoactive effects associated with coffee consumption.

Chemically speaking caffeine is what is known as a purine. It stimulates the central nervous system (CNS) by blocking the action of adenosine (a molecule involved in cellular communication through the second messenger cAMP).  cAMP acts on the CNS promoting drowsiness and preventing arousal, basically making us tired. In the morning when we wake up,  levels of cAMP in the body are relatively low.  As the day progresses cAMP builds up and binds to adenosine receptors found in the CNS. cAMP then acts as a messenger triggering downstream effects which make us drowsy. Caffeine prevents drowsiness by acting as an antagonist of cAMP, temporarily blocking it from communicating its downstream message.  This blockage also promotes the release of other chemicals such as acetylcholine which can stimulate the body.  This stimulation leads to increased alertness and focus, aiding in concentration and performance.

However, like with most foods, we’re constantly hearing about the associated diseases and medical problems coffee could cause; cancer, heart disease and long term addiction to name a few.  But, how much of this is true?  Well actually very little.  Like many of our guilty pleasures, caffeine in  moderate amounts has no negative effects on healthy adults. In fact you would need to consume a whopping 15-20 cups of coffee per day to overdose (I think most people would struggle with that)! In terms of caffeine addiction, it is possible to experience mild psychoactive withdrawal if consumption is stopped, but this affect is mild compared to the withdrawal experienced when coming off other psychoactive drugs.So, whilst you should definitely not substitute coffee for water, our favorite fuel is still a safe morning essential – go procaffinate!

 

Post by: Stephanie Macdonald

Useful links:

http://www.webmd.boots.com/healthy-eating/guide/caffeine-myths-and-facts

https://en.wikipedia.org/wiki/Caffeine

http://www.ncausa.org/About-Coffee/What-is-Coffee

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Are we finished editing CRISPR?

The academic world has been abuzz in the last few years with talk of a new gene editing technology known as CRISPR.  We hear about it on the news and are told that it could one day be a game-changer for modern medicine in terms of genome editing. But, like this article, all new techniques require proofreading and adaptation. So what I’m really wondering is: are we finished editing CRISPR?

CRISPR stands for ‘clustered regularly interspace palindromic repeats’, a mouthful even in the scientific community! CRISPR is a constituent of prokaryotic DNA and is used by these cells as a simple immune system, protecting them against viral attacks. We can imagine prokaryotic DNA as a piece of string (below: labeled as bacterial DNA), with repeated segments (circles) broken up by spacers (rectangles). Bacteria are able to detect invading viral DNA and add short sequences from the viral DNA in between the repeated sequences of their own DNA, creating a catalogue of past infections (a bit like our own immune system). If a virus attacks the same cell again these spacer regions are recognised by a special group of proteins called Cas proteins.  Cas proteins are nucleases which use the CRISPR-incorporated viral DNA segments to chop up the infecting viral DNA and inactivate it.

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Scientists have harnessed the power of the CRISPR/Cas9 system by replacing viral DNA spacers with synthetic guide RNA’s that match a specific DNA sequence – this can be anything the scientist wants to modify. Researchers can then direct the Cas9 protein to their selected gene, causing a break in the DNA and the deletion of that region of the gene, ultimately allowing them to control expression of selected genes.

In theory CRISPR has the power to edit and even remove harmful genes associated with both acquired and hereditary diseases. In fact, just this year Anderson and colleagues at MIT demonstrated its potential in mice, correcting a harmful metabolic mutation. So why are we not using CRISPR in the clinics already?

While most people have no issue with treating acquired conditions, such as cancer, in previously healthy people, concerns arise when we talk about germline editing: i.e. editing human embryos prior to birth. From a medical perspective embryo editing could enable children with life threatening and debilitating conditions to lead a ‘normal life’. However, some parents believe that editing their child’s genome will change the child’s identity. Researchers also argue that, not only will germline editing reduce genetic diversity but we also don’t know enough about the genome and its regulation to confidently make such drastic and heritable changes. On a personal note, my main concern is where would germline editing stop? Where do we draw the line at disease state? For example obesity, my own area of research, and its predisposition is now considered as a disease.  The more conditions we begin label as ‘diseases’ the easier it could be to edit for desired traits.

All these issues exist before we even begin to think about the safety aspects of this new technique.  How do we deliver this system effectively into the human body? And, once there, how efficient and specific will it be. For example off target effects have ranged between 0.1-60%, levels still too risky for the clinics.

While acknowledging that CRISPR does have great potential in the future, much editing and rewriting may still be required before we can click submit.

Post by: Stephanie Macdonald

Sources:

http://www.nature.com/news/crispr-1.17547

http://www.nature.com/articles/nbt.2884.epdf?referrer_access_token=vn4y2fRlT6MSfnjiTkEah9RgN0jAjWel9jnR3ZoTv0NYT9zJj6mpbqWqBhkZTqLWByT9ZihiHupT0fSw150iFynOlHiUTmOgoLqeCBiezScmQzKXSWZlhANyZY8taAUjw7mxZP3DyqCYVeWMBSDBoB_ExZ0FQkLTfyBfhnOubzmO0jxfwklUENzc3pAW-hXzt-7A-uc2YpLGwekIaMKzouz-lsbrPIE9Dozc5RIYLf8%3D&tracking_referrer=www.nature.com

Figure adapted from:

https://en.wikipedia.org/wiki/CRISPR

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