Gene Therapy - The Walton

Here is a copy of the article I did for the Spring Edition of The Walton. You can read more here.

Over the past year in Ireland, there has been much excitement with regards to gene therapy, with a couple of potentially ground-breaking developments occurring. So let’s pause and look at what gene therapy is, how it is currently being used and perhaps look towards the future.

Gene Therapy is an umbrella term for many types of treatments. Ultimately it involves changing, fixing or replacing genes that are defective or mutated in someone’s cell such that the cells can function again. Remember that genes represent the code by which just about everything that happens in the body follows; an instruction manual for all the processes of the body. So if some of that code is missing, or incorrect, the body functions won’t work properly. Examples of such diseases would be cystic fibrosis, Huntington’s disease, Sickle-cell anaemia and a huge range of immunity disorders. Even cancer is caused by genetic mutations. So if there was a way to fix the code, repair it in some way, this would have huge benefits to thousands of people.

One way to fix a broken code involves using viruses. This may sound alarming, but it is actually quite effectively used. The basic principal revolves around using a harmless virus i.e. one that will only infect certain cells and won’t replicate, to carry the corrected gene code to cells. Viruses do this anyway – when they infect a person, they are often actually infecting the cells, their own gene codes being incorporated into the host cell. Usually this is extremely detrimental, and cell death ensues, but by controlling what gene sequences are included in the virus, you can potentially tailor what happens when a virus infects a cell.

The diagram shown here shows a virus (called a vector because it is basically a transport vehicle) attaching to a cell. It is an adenovirus vector. Adenovirus is associated with respiratory, intestinal, and eye infections in humans (especially the common cold). As shown in the diagram, the virus is taken into the cell and then travels to the nucleus (the pink thing). It attaches to the surface of the nucleus and injects the DNA into to core of the nucleus. Remember that the nucleus of the cell is where we hold all our own genetic material.

The DNA type molecule in this case isn’t a double-stranded molecule, but instead is a single strand, and can thus be read by the cells replication molecules. These molecules are called messenger RNA, and they are part of the process by which new proteins are formed. Thus, if the correct DNA is present, the correct proteins will be made, and so any dysfunction that occurred before may be rectified.

There are two methods to introduce the genetic material into the patient. Ex vivo gene therapy involves removing cells from an individual’s body, modifying them to include the correct genetic material using a vector, and then transferring these cells back into the patient’s body. In Vivo gene therapy involves injecting the viral vector directly into the patient, in the hopes that the virus with infect and ‘fix’ the damaged cells. Both methods have seen varying levels of success.

Cystic fibrosis is a genetic disease which is particularly common in Ireland and results in a build-up of mucous in the lungs of affected individuals. Vital research in University College Cork is currently underway to cure cystic fibrosis. The central tenet to this research involves creating breaks in both strands of the DNA at targeted sites. This process is enabled by the use of Zinc-finger nucleases which are specially designed DNA-binding proteins, with high specificity.

By intentionally creating a break in the DNA strands, you can induce homologous recombination (a time of genetic repair) between the broken strands. This can allow you to include the correct sequence in the genome at that point. More in-depth analysis of the current status of research, both here and in the UK will be presented in next issue of Walton Magazine.

Similarly, a novel treatment for bacterial infection of Pseudomonas aeruginosa in cystic fibrosis patients is also seeing some success, also using gene therapy. The research was carried out the Alimentary Pharmabiotic Centre [APC], a Science Foundation Ireland funded research centre based in UCC, Teagasc Moorepark Research Centre and CIT.

The researchers, led by Professor Colin Hill in UCC and Professor Paul Ross in Teagasc, took advantage of a method called phage therapy. This involves identifying and characterising bacterial viruses which can attack and kill Pseudomonas aeruginosa within minutes of initial contact. One of the advantages of phage therapy is that any viruses which ‘find’ a target multiply at the target site, generating more viruses and amplifying the therapeutic effect. This research is paving the way for the development of new treatments for Pseudomonas infections in cystic fibrosis patients.

So with two keen and different ways of tackling the disease, either by treating the infections that occur or by curing the disease itself, it goes without saying that there is bound to be some new revelation this year. We have barely scratched the iceberg in this article with all research for other diseases that could be treated, so maybe that’s for the next time!

New Blog

Here is another blog I write: cleverbugblog.wordpress.com

Pigs, Ferrets and Flu

And so the panic may begin again. 

A new flu virus found in pigs in Korea may have the potential to infect humans. We aren’t that similar to pigs in our genes, but we are pretty close to ferrets… and they are getting sick too. And the virus grew in human tissue in the lap.

It is interesting to note, and I did not know this, is that ferrets are the favoured proxy for humans in flu research.

 “That makes it a bit scary,” says Robert Webster, a virologist at St. Jude Children’s Research Hospital in Memphis, who co-wrote the research paper. So far, the virus has not been found in people, but “if it is in the pig, beware,” he says.

All that has to happen is a bit of genetic mixing or reassortment in the virus for it to start infecting us. Unfortunately, pigs are known to be perfect mixing vessels for the virus, so this is a major cause for concern. H1N1 (back in 2009 – remember?!) made ferrets sick.

Many different mutations could occur, from changing the proteins on the virus’s outer surface (which affects adhesion to our respiratory cells) to changing other proteins which are involved in making them more infectious.

But don’t panic, just because our weasely friends get sick, doesn’t mean we will. Yet. *insert dramatic music here*

Article Source: www.sciencenews.org

So What is Software Licensing, Anyway?

So I started a new job working in software licensing - I had no idea what I was getting myself into. Little did I know, that this is something we are all involved in, and it pays to know a little more about what it's all about. Sure, it's not quite science, but unless you are careful you can end up getting into trouble. So here it is - what software licensing is all about!

People often seem to think that software is a commodity – something you buy from a retailer which you then own and use. But in actual fact, with software, you license, not purchase it. Why? Well, when you license the software, the primary value comes not from an object (such as the disk it is stored on) but instead from the knowledge of the people who wrote the software – the ‘cleverness’, if you like. You can’t own that knowledge, you merely acquire a limited right to use it. Put simply, software is intellectual property.

It’s tricky to define or identify the value of intellectual property and thus, such things are copyrighted (copyrights, trademarks, and patents). This allows whoever owns the material, in this case, software to define who can access and use their property, protecting it from unauthorized use. This is in an attempt to define the value of the software.

In this line, a software license provides the legal right to install, use, access, display, run, or otherwise interact with a software program. This doesn’t always include right to media, manuals, or support. Remember checking the ‘I agree’ box whenever you install something? That is you agreeing to the terms of use of the software.

If you breech these terms and conditions, you are in violation of the law and can run into trouble.

So yea, it's important. I may start blogging about more technologically oriented things from now on... maybe!

Licensing Software

It has been far too long, and I promise to find some newsy item to write on, but for now, check out this new blog that I am managing... http://wp.me/p11yyP-4W (its all about what software licencing, which is actually really important (it's news to me!)

enjoy

Cloudy Computing?

Being asked to define or explain cloud computing is like being asked to pet Schrodinger’s cat: you just can’t. Not easily anyway. The name suggests as much, but is it really that vague? A buzzword made so popular recently with the likes of iCloud, Dropbox and Microsoft Sharepoint, is it just that, a buzzword? Or is there something more? With headlines littering the news daily, and with every company beginning to carry the tagline ‘We use cloud’, some myths need to be dispelled and facts shared.

Technically speaking, cloud computing is the practice of using a network of remote servers or computers hosted on the internet to store, manage and process data. This is usually managed by a third party company, (a vendor) who is responsible for everything; management, administration and trouble shooting. Often, these servers (or hosting devices) are located in various locations. 

Often, companies offer either a dedicated or shared server agreement. If dedicated, only your information is stored on a server, which is more expensive. Shared is the converse of this. Clearly, if you are in a shared environment you run the risk that others might have access to your data or bring down the server completely. Also, location wise, it is rare that you know exactly where the data you are storing is. This has become an all-to-apparent problem with shutting down of MegaUpload.



Traditionally, these activities would be done using a local server or personal computer. So any data you are saving or accessing is stored locally, on your premises. In large businesses, this would typically involve a large room filled with servers in the basement of the building, to which each staff computer has access. For personal users, it just entails using hard disks or simply storing data on your PC or laptop. So, most websites and server-based applications ran on particular computers and servers. What is different with the cloud is that the cloud utilizes the resources from the computers as a collective virtual computer. Applications can run independently from particular computer or server configurations. With broadband internet, the need to have the software run on your computer or on a company’s site is becoming less and less essential. 


A lot of the software that people use nowadays are completely web-based. The cloud takes advantage of that to bring it to the next level. Thus, the hardware is less important.

A summary of what is being offered by vendors is as follows. The most basic is called Infrastructure-as-a-Service (IaaS), which is just servers ‘in the cloud’. This is mostly for tech companies who just want access to computing power but don’t want to be responsible for installing or maintaining it.


The next tier is Platform-as-a-Service (Paas) which is a cloud-based platform that companies can use to develop their custom applications or write software that integrates with existing applications. These environments are often equipped with software technologies like Jave, Python and Ruby on Rails (coding languages) to allow customers to start writing code quickly. The vendor then hosts the code and makes it widely available. This is often used by companies looking to outsource a piece of their infrastructure.


Lastly is Software-as-a-Service (SaaS), which is the largest and most mature part of the cloud. It is an application or suite of applications that sits in the cloud instead of on the user’s hard drive or in a data centre. One of the earliest SaaS successes was Salesforce.com’s customer relationship management software. It was an ideal alternative to on-premise CRM systems when it was launched in 2000. Further developments now include productivity and collaboration software such as Google Apps, Microsoft Office 365 among other things.

Have you noticed how much more dynamic webpages are? This is somewhat due to the development of Html5, which allows everything you are browsing to be cached (temporarily stored) to the cloud (e.g. Google server) which means you have less caching on your computer, taking up less space, and thus, ultimately less processing power. This means instant loading web pages, which are more dynamic. It also allows companies to give their users/customers more scope in business world online; just another aspect of internet progression.

Other less technical benefits of the cloud include a significant reduction in cost. In fact, previously, companies had to fork out excessive budgets to manage servers and server management teams, whereas now, it can all be done by a third party, who often offer ‘pay as you use’ contracts, marking the end of user organization demand. Companies no longer have to manage the servers (they break down often), they don’t have to have an IT staff, and basically, the old headache has been alleviated’. Somewhat. Maybe.


It also offers a collaborative atmosphere – take Microsoft Sharepoint, for example, which allows transfer and access of documents between groups. And it is being given out like candy to companies at the moment. Also, some smaller companies can use cloud analytic services, as they have access to big data that has been generated by other companies, and thus, can analyze their customers, or employees, or anything they want to. Another attraction is that access is given to cutting edge technology, with no need for the risk of ownership.

The problems that are starting to come out of the woodwork are things like data ownership, security and contract obligations. Data ownership is an interesting one. You, the client, have asked a third party to look after your files and information. They have it stored on their servers, which is accessed using their applications and portals.

Megaupload.com was a file hosting service, run by a Hong Kong-based company. The site was shut down by the U.S. Justice Department on January 19^th following the indictment and arrests of the owners in New Zealand, who are charged with copyright infringement. They argue that they just offer a service, and that it is not their responsibility that the users upload content (onto the cloud) that is illegal.

So who takes the fall? The users cannot be easily tracked, and the owners now face the charges. This is an important thing to consider about the cloud. That said, it is only if the content being stored is illegal in the country it is being stored in, that problems will occur. Who polices this, and how does a vendor or client know what the law is of the country that the servers are based in? In effect, the cloud is breaking the usual boundaries, making it exceedingly difficult for law-makers to predict.

Other minor issues include integrating new technologies with existing legacy systems in established companies, and thus issues with compatibility can arise. But usually, whole aspects of a process is outsourced to the cloud, so this may not actually be a particular problem. One way of looking at cloud computing, is as the industrialization of enterprise technology. This suggests a decrease in jobs, especially in areas that manage data centers.

So it seems that the cloud is not quite as ‘wafty’ as it would at first appear.  Also, considering that this technology, although newly revolutionized and popularized, is not actually new, it is most likely here to stay.

Marijuana and Memory

This time of year, memory is on everybody’s minds. With late night cramming and early morning panicking – ‘tis the season of exams. So with all this stress you may want dabble with various calming chemicals – rescue remedy, copious amounts of tea and cigarettes, perhaps all with dash of alcohol, and maybe a shneaky shmoke, but is that actually a good idea?

Mary-jane, gunja, weed, pot, whatever you call it, research shows that marjiuana significantly impairs working memory – the memory that you would need to use to cram in those last minute facts about Chaucer or Freud or Boyle. But until recently, it was not clear exactly what the source of the memory lapses were.

The major psuchoactive ingredient (THC) impairs memory independently of its direct effects on neurons. The side effects stem instead from the drug's action on astroglia, which are passive support cells to neurons in the brain supporting, protecting and feeding neurons. Support cells typically help the propagation of electrical signals along neural cells.

It was actually thought that that was all that the astroglial cells do – support. But now evidence has accumulated that suggests these cells play a more active role in forging connections between one neuron and another.

The researchers didn't set out to discover how marijuana causes its cognitive side effects. Rather, they wanted to understand the receptors found on the cells. Mice lacking these receptors on the astroglial cells are protected from impairments to spatial working memory that would usually follow a dose of THC. These receptors are found on other neurons as well, yet if the receptors are lacking in only in neurons, then the mice still suffer the memory problems.

"The study shows that one of the most common effects of cannabinoid intoxication is due to activation of astroglial receptors," the researchers wrote.

Given that different cell types express different variants of that receptor, there might be a way to therapeutically activate the receptors on neurons while leaving the astroglial cells out. Thus, these findings offer important new insight into the brain and raise the possibility that marijuana's benefits for the treatment of pain, seizures and other ailments might someday be attained without hurting memory, the researchers say.

The findings further suggest that astrocytes might be playing unexpected roles in other forms of memory in addition to spatial working memory, Zhang said. The researchers hope to explore the activities natural endocannabinoids (things that are like cannabis), which naturally trigger the receptors, on astroglial and other cells. The endocannabinoid system is involved in appetite, pain, mood, memory and many other functions. "Just about any physiological function you can think of in the body, it's likely at some point endocannabinoids are involved," Marsicano said.

And that means an understanding of how those natural signalling molecules act on astroglial and other cells could have a real impact. For instance, Zhang said, "we may find a way to deal with working memory problems in Alzheimer's."

But back to the marijuana effects – it is clear that this drug triggers memory impairment, so perhaps it would be best to stave off the stuff for a while, and give your astroglial cells a rest!