This post on Microbe World entitled: “Software for Programming Microbes” did attract my attention, and I followed its source in the MIT Technology Review: An amazing article presenting a fascinating newly emerging technology of programming bacteria to do whatever we want them to do, produce drugs more efficiently, clean up oil spills, anything… useful! But the methodology was quite beyond my imagination.

I was extremely lucky to be able to interview Dr. Christopher Voigt, Associate Professor at the University of California, San Francisco, who is the project leader. Dr. Voigt has published over 34 articles indexed in Pubmed and you can find more about his projects on his lab website.

Now I will leave you with the interview! I thank Radwa for reviewing it.

Dr. Christopher Voigt

For a long time, mental retardation was believed to be incurable, as it is usually caused by gene mutations that disrupt brain development right from the beginning and even before birth. But thanks to a lot of hard-working scientists, there are trials now to improve the quality of life of such patients, along with their caregivers. The work has been focused on a condition known as “Fragile X syndrome”. In this disease, a mutation takes place in a gene called FMR1 , which is responsible for the production of proteins, that regulate neural development, usually leading to mental retardation according to the extent of such mutations.

Fragile X syndrome's common physical symptoms : elongated face, large ears, etc

Another important contributor to the condition is the metabotropic glutamate receptor-5, abbreviated to mGluR5. It is responsible for controlling the process of protein synthesis at the neuronal synapses, becoming hyperactive in case of fragile X. Being an interesting therapeutic target, a major pharmaceutical company developed AFQ056, an mGluR5-receptor blocker, in the hope that it’ll restore normal transcription levels. The results of the initial double blind clinical trials, conducted on 30 patients, were evaluated through the notes taken by the caregivers about the behavioral improvements of the patient. This included less repetitive behavior, less hyperactivity, less tantrums and having better chances of establishing communication with the patients.

What seemed like a puzzle is that some caregivers reported no change at all after the patients took the drug. So after data analysis, the researchers found that the only patients affected by the treatment were the ones (7 patients out of 30) having a certain genetic marker: complete methylation of the FMR1 gene regulator sequence, and therefore, complete lack of FMR1 transcription. Another disappointment was that the drug didn’t improve cognition or memory, but this, they say, might be attributed to the short duration of the trial, lasting for only 4 weeks.

The next step is to repeat the trial, but this time on 160 selected patients, after testing them for the marker and the experiment will last for 3 months, hoping to obtain better results that are more significant to the patients of this illness.

Sources: Wikipedia and Science News

Which hair colour a person possesses depends mainly on the proportional amount of two melanin pigments, mainly the black-brown pigment, known as eumelanin, and the blond-red pigment, known as pheomelanin. The assortment of hair colours present is a consequence of the numerous combination proportions of each pigment.

For quite some time now (since 1997), the gene responsible for the classic red-hair phenotype has been discovered. At that time, the research team was concerned with the MC1R gene on chromosome 16. Its role was the production of MC1R receptor, which assists in the conversion of pheomelanin to eumelanin. Individuals with two copies of the recessive gene, causing a mutation in the MC1R, are most likely to turn out red-headed due to the build-up of pheomelanin. However, since the other hair colours are controlled by a variety of genes, it was, until recently, a tough task to predict a person’s hair colour from strands of his/her DNA.

Now, researchers at the Erasmus University Rotterdam have released an article identifying 13 DNA markers, located on 11 genes, which can guide us to the prediction, with a fairly high accuracy, of an individual’s hair colour. “For our study, the authors utilized the DNA and the accompanying information regarding hair colour from hundreds of Europeans and analysed various genes, that were previously known to be involved with this trait”, pointed out Professor Manfred Kayser, who lead this study. The accuracy percentage is as high as 90% when it comes to black and red hair, but dropping down to 80% or more with blond or brown hair.

The further potential implications of the study will soon be applied to forensic investigations. Along with their previously published work regarding eye colour and height from the DNA, these researchers aim at forming a descriptive profile of previously unidentified individuals, whether victims or offenders.

Source: Scinexx

Man or Machine? Bioinformaticians at McGill university are betting on man. They want to put, what was previously wasted, time on the internet into use. Thus, Phylo was created. That is the name of an online interactive game, aiming to solve the problem of multiple sequence alignments, one that has been agonizing researchers for some time now. The human mind is evolved in a way, that even computers supposedly can’t beat. We are capable of recognizing certain patterns and forming interrelations between them, a skill which numerous lines of codes can not easily accomplish.

So what to do? Once you open the link, go ahead and sign up, although it is possible to play as a guest. But hey, if I am taking time off to contribute to science, I want to be able to brag about it later on. 🙂 The creators of the game have formed a very comprehensive tutorial, explaining how the game works. They use down-to-earth terms and comparisons to simplify matters, so people from all walks of life can jump in as well.

The coloured blocks: Those symbolize the nucleotides. Correspondingly, there are four of them: Orange, Green, Blue, Purple. I wasn’t able to find exactly which colour codes for which nucleotide, something which particularly intrigued me, since purple blocks were scanty in my alignment.

Aim of the game: Our job is to align these blocks, as best as possible, so that the blocks’ colour in the first line are matching those in the second line. Matching blocks gives you a score of 1 point and mismatched ones deduct 1 point. This should be preferably done WITHOUT having to create gaps. They point out that gaps represent the mutations, which the sequences have incurred during evolution. In the easier stages, the sequences are provided on two lines, representing two different species. As it gets more difficult, more lines are provided and related together through a mini-phylogenetic tree, to allow you to pinpoint your priorities. Once you have reached the same score a computer had previously provided “par”, a star will blink to indicate that you are ready to move on, as the alignments are stored in a database for future use.

My experience: I stumbled upon a feature, where you can choose the type of sequences you want to work with. They are arranged according to disease, level ID, or simply random. I chose the blood and immune system disorders and was granted sequences, related to essential thrombocytopenia.

Statistics: At the end, I was provided with the following astonishing numbers. So far, 5344 users have submitted 70196 alignments for 2137 different levels. Personally, I think this number is quite surprising, since that many people are joining in since only November 29th, the date of the official launch.

Interested in more: In the “about” page, the following sentence is provided: “For more information about any one of these topics, click here“.

On a Tuesday, the year 1995, Graham, a 57-year-old patient on the verge of congestive heart failure, received a call that a donor has been found. This donor committed suicide via a self-inflicted gunshot wound. After the successful transplant, Graham got in touch with the donor’s family, married his wife and after a whopping 12 years later,  kills himself through the same technique. In an interview held a couple of years after his marriage, he admitted to the reporter that after seeing the donor’s ex-wife, he felt as if he had already known her for years.

Ever since heart transplant surgeries were a success in 1967, scientists were skeptical about what is now referred to as, Cellular Memory Phenomenon.  This was provoked through the close observation of recipients, who repeatedly report bizarre distant memories and new personal preferences. Exactly how much can the cells of an organ, other than the brain, mainly the heart in this case, store memories? The Discovery Channel aired a documentary titled “Transplanting memories” where various experts gave their opinion on the matter.

If such phenomenon truly exists, where are these memories located inside the cells? Could it be the DNA? But this is sheltered inside the nucleus and remains entangled except when cellular division takes place. This makes its access difficult, but after all, it cannot be THAT difficult, otherwise mutagenic agents wouldn’t have succeeded.

Possibly proteins. Dr. Candace Pert stated that, since the brain and human organs are linked through a massive network of peptides. She said “I believe that memory can be accessed anywhere in the peptide/receptor network. For instance, a memory associated with food may be linked to the pancreas or liver, and such associations can be transplanted from one person to another.”

Source:  The Medical News

Image Source: Hiveworld

What is bioinformatics?

It can simply be defined as a link between biology and computer science, in which the biological data is processed and computed through software, to yield an output, that is later interpreted in different ways.

Biological data indicates the nucleic acid or protein sequences, their simple or complicated forms, whereas the software is the computer program, specially designed for processing these data in a certain way, done using a certain algorithm (it is a recipe to solve a program problem). The data output is usually numerical or visual (often graphical), but mostly it needs to be well understood. The last one is the key point in the bioinformatics.

What is the need of bioinformatics?

In the research field, we need to be led to certain road, to choose one way or another, or to try many options until we define our research plan. Bioinformatics simply brings the solutions into your hands by a few mouse clicks.

One simple example to make it all clear is the PCR (Polymerase Chain Reaction). We always need to design a primer to trigger our reaction. If we did this through the ordinary ways, we would have to practically try out so many primers and this would surely take a tremendous amount of time. Now, what if you are computer- and internet-literate? You can simply use software to get many primer options for the DNA piece under investigation; doesn’t this save time, efforts and money?

Can bioinformatics be useful in different ways, other than the PCR example?

Some people may think that using bioinformatics is limited to some fields of biological research, and some others might think it is only a matter of prediction, which always needs to be evaluated for its accuracy, specificity and efficiency. But indeed, bioinformatics can be used in the analysis of nucleic acids and proteins.

Analysis?!! That is a vague word, how can you analyze a protein using bioinformatics?

Now you’ll see what bioinformatics can do for protein analysis:

1. Retrieving protein sequences from different databases, either specialized or general databases and it is not an easy job if you would think so.
2. Computing a protein or amino acid sequence to obtain:

• So much of the physicochemical properties of you sequence like the molecular weight, and isoelectric point…etc
• Hydrophilicity / hydrophobicity ratio

Both of the above can provide us with the probabilities of one protein acting as a receptor on the cell surface or it might be antigenic or even secreted outside the cell.

3. On the prediction aspect, we can predict:

• Some sequences of certain importance, e.g. the prediction of signal peptides that can lead us to know the secretory proteins of one organism
• 2ry structure of your protein
• 3ry structure of your protein

The last two points are applications of what is called structural bioinformatics, through which computer is capable of predicting the 2ry and 3ry (3-D) configuration of your protein, using special programs with advanced algorithms and artificial intelligence. Amazingly, this may be useful in understanding the receptor-substrate interactions.

4. Comparing sequences to obtain the best alignment (it means compare 2 or more sequences to find their relation to each other, i.e. finding similarities and differences), it will help in:

• Classifying your protein and relate it to its protein family
• Making your evolutional expectations about your protein to define whether it descends from another protein or not. This is called phylogenetic analysis, at which the proteins under investigation are studied to know which protein is considered a mother to the others, which are the daughter, the grand daughter, and so on
• Detection of the common domains, this will help us understanding the functions of unknown protein when it is compared to sequences of other proteins of known functions

Then, what will we gain if we compute DNA? Or you can say, what can bioinformatics do for DNA research?

On the same level as with protein, though different applications, we can use it in:

• Retrieving DNA sequences from different databases
• Computing a sequence to obtain information about its properties (like proteins) e.g. GC% which could be used with other properties to identify a gene
• Assembling sequence fragments (usually DNA is sequenced in the form of fragments which are needed to be assembled in the best way, bioinfo. does this in a faster and more accurate way rather than the ordinary assembly)
• Designing a PCR primer
• Prediction of DNA and RNA secondary structures (e.g. prediction the stems and loops of the t-RNA)
• Performing alignments between 2 or more sequences that can lead to many applications (as those mentioned above in protein alignments)
• Finding of repeats, restriction sites, Single Nucleotide Polymorphism (SNPs), and/or open reading frames, all of which have so huge applications in the medical and paramedical fields and typically in the research activities.

From a humble point of view, as I was attending a bioinformatics and genomics workshop held in FOPCU, the lecturer was pointing to us, that up until now, no one has managed to come up with a method capable of converting a full-functioning protein back into the original nucleotide sequence on its corresponding gene. At that instance, the following thought occurred to me, as to why this would ever be needed?

For starters, we already have the protein in hand, its 3D structure is, for many, completely figured out and some even their orientation in space, their actions and functions. Then, as far as I understand, being the mould from which a protein is later assembled is the only function a gene, or one which is expressed anyways, has. Knowing that for instance, in gastrin hormone, the 4^th amino acid is leucine, would it matter whether it was translated from the codon CUA and not UUG?

Now three thoughts impose themselves. I could only imagine that the presence of SNPs (which is basically a nucleotide that varies among individuals and thought to influence certain traits) within the nucleotide sequence of the gene is the reason behind the researchers’ attention. However, this ultimately means, that if a method were to exist, it would have to produce a different nucleotide sequence for proteins coming from different people. Simple logic.

Another probable explanation, that could come to mind, would be the existence of a difference in the structure of the leucine amino acid, held on tRNA molecules with varying anticodons, where each would have some “characteristic” features that distinguish it from the other tRNA. If that were the case, then it probably has managed to fly below the radar for quite some time, as no matter which reference I turn to, it is taken for granted that these amino acids are carbon copies. So being non-identical in any way, would cause the resulting protein to function in a slightly different manner, which could explain the diversity of their actions in varying individuals. Who knows?

Last, but not least, is the possibility of gaining fast insight into the genome of a previously undiscovered species of living organism, where one can quickly figure out all the expressed genes through this simple task of “reverse translation”. However sequences of the unexpressed genes would still have to adopt the old-fashioned way. No choice there!

Just wondering what the future has in store.

Yesterday, I was watching an episode of “The Doctors” where they were talking about a new study that completely amazed me…It was carried out at the Karolinska Institutet & the findings come in favor of men, mostly!! They found a link between a person’s genetic makeup & their relationship status. I have to admit that is pretty interesting.

The gene studied was AVPR1A, which actually has to do with one of the receptors for ADH, predisposes men to make unhealthy decisions, when it comes to relationships, once they have the allele 334. That is how it got its name, which it is pretty much now famous for as “The Commitment Gene”. Presence of two copies makes matter even worse…It is funny once you start thinking hmm..and how did they discover that!! The study was carried out on 550 sets of twins where they had to complete a survey evaluating their life in general & specifically when it comes to relationships..whether they are married, divorced, not ready to commit yet..

Luckily for the ladies, these genes can’t really dictate what a person does because that is all about his choices…but after all, it would be added on to the growing pile of excuses :). I wonder in the future if women would ask their future spouses to first undergo an examination and search for that gene…Who knows what the future might bring us!