Archive for the “Uncategorized” Category

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:

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.

Tags: , , , , , , , , , , , , , , , ,

Comments 1 Comment »

Hansenula polymorpha, also known as Pichia angusta, with its metabolism highly dependent on methanol as a carbon source, has been excessively employed in the production of therapeutic proteins for the last two decades. The yeast was first discovered in 1950s in spoiled orange juice.

Image source:

The biotechnological interest in Hansenula is mainly attributed to its unique capabilities underlied by its rare characteristics. For instance, being one of the limited group of yeast that are able to assimilate methanol, gives it the advantage of being able to utilize relatively cheap substrates. In addition, Upon high temperature,  Hansenula polymorpha shifts its biochemical methanol metabolism pathway to the biosynthesis of trehalose which is a thermo-protective sugar, this fact explains its unique ability to resist temperatures up to 49 degree Celsius. further, Hansenula is able to secrete the protein products directly to the culture, a fact that renders the whole process of downstream processing easier and less costly. finally, the ability to survive in wide pH range,from 2.5 to 6.5, makes it a versatile protein factory which is exploited in the production of various types proteins, each of which requires a very different optimum pH value throughout the fermentation process.


Image source:

( Budding Hansenula cells)

However, with Hansenula polymorpha post-translational modification processes are not highly regulated, this makes Hansenula useful for the production of relatively small to medium sized polypeptides as Parathyroid hormone, Staphylokinase, Elafin……etc.  However, Regarding large polypeptides, mammalian cells with tightly regulated post-translational modification processes represent a better option.

On the industrial scale, different strains of Hansenula polymorpha are being exploited as expression systems. For instance, a genetically engineered strain known as super-transformed strain bearing additional two advantages than the wild type strain. Being super-transformed means that it is capable of secreting Calnexin which is a protein Chaperone that functions to ensure proper folding of the secreted protein. Additionally, Calnexin enhances the protein secretion efficiency of Hansenula . Accordingly, the super-transformed strain gains its industrial potential in terms of quality assurance of the secreted protein product as well as increasing the  cost effectiveness of the industrial process.

References: 1.Hansenula polymorphawikipedia,

2. Gellissen G, “Hansenula ploymorpha : Biology & Applications”, 2002

3.Marcos A. Oliveira, Victor Genu, Anita P.T. Salmazo, Dirce M. Carraro and Gonçalo A.G. Pereira1 ”The transcription factor Snf1p is involved in a Tup1p-independent manner in the glucose regulation of the major methanol metabolism genes of HansenulaPolymorpha”, Genetics and Molecular Biology, 521-528 (2003)

4. Giuseppinia Parpinello, Enrico Berardi, and Rosanna Strabbioli,” A Regulatory Mutant of Hansenula polymorpha Exhibiting Methanol Utilization Metabolism and Peroxisome Proliferation in Glucose”, J Bacteriol. 1998 June; 2958–2967.
Tags: , , , , , , , , , , , , ,

Comments No Comments »

“Mutations are the cause of almost every disease”. That is what a researcher told me when I asked her why we are very interested in studying mutations of the human DNA. Is that possible? Will the future medicine mainly depend on molecular genetics? Will each of us have his very specific genetic fingerprint included in his profile at his doctor? All those questions suddenly hit my thoughts when she continued to explain the huge impact of this new science on medicine.

You may say that if it’s mutation, we can simply “fix” it through gene therapy but still gene therapy is not approved by FDA and there are high risks and also considerable percentage of failure in this type of therapy. Well, I can tell you that this is not the only reason driving us to study gene mutations or mutations in general.

There were two old misconceptions (and may be still present). The first was that all diseases are only caused by environmental factors while the second was that congenital genetic diseases must be shown on parents. Studying mutations on DNA level proved that those are not necessarily true. Many widespread well-known diseases such as hypertension and also diabetes were recently known that they are of genetic origin. On the other hand, some cases of congenital mental retardation causes such as phenylketonuria (PKU) found in the newborn and not clearly shown in both parents.

There are also many good reasons why the interest in studying mutations raised  lately. I can tell that one of them was the Human Genome Project. Since we  can know most of the genes and we can easily get the sequence of any DNA sample, why don’t we study the “changes”? I think that’s the base of every science. We figure out the “normal” and then look up for the “abnormal”. Or, how can we be so sure about the “normal” unless we study the “abnormal”? That makes real sense to me.

She kept opening boxes, some I know and some I really didn’t know about. She also said that DNA analysis and sequencing is very important before marriage. Susceptibility of the expected child to some diseases (on the genetic level) may be also verified. Although it seems more of genetics but it’s true. Some mutations are inherited just following the Mendelian law. She gave me example; say that expected mother has mutation “deletion” in one of the genes while the expected father has mutation “insertion” in the same gene, the expected child may not be affected. On the other side, if both have deletion or insertion, there will be another pathway for this marriage.

On the prenatal level, we can actually save lives and avoid many complicated consequences that may happen. A sample from amniotic fluid or the pregnant mother blood (better to be the amniotic fluid), we can study how our fetus’s DNA is. If it is impossible to survive or it shall have tragedy in its life, legal abortion is carried out. If it is a milder case and the baby can survive for long period, we can maximize its opportunity as in the case of previously mentioned PKU. We know that certain types of food elements will enhance mental retardation; we can totally avoid them and guarantee a healthier happier life for both child and parents.

            She emphasized on one thing I didn’t, previously, take care of; the diagnosis. She explained by saying that in many cases, especially cancer, we need to take a biopsy to send it to the pathology lab to say whether it’s benign or malignant. In prostate cancer for example, it’s more close to a surgery and we may be led to prostatectomy which is very painful whether physically or psychologically. Mutation analysis may save all that and provide us with non invasive method for diagnosis. ( I have to clarify that in some diseases, biopsy is better and more specific than blood sample for example,  congenital heart diseases)

We all know that many diseases are multi-factorial which means that one thing happened leads to this and this leads to that and the same that causes another that..etc. So, it might be difficult tracking down the “single main factor” which was the first troublemaker. DNA can tell us about it. By detection of mutations, it may clarify what is the real reason of this dilemma. She opened a totally new box to me; unresponsiveness to the drug; the usual therapy not gene or any correction. I had a very small background about pharmacogenomics that sometimes we need to “tailor” the dose for every patient due to the fact that we are not simply the same. But, she gave me an additional interpretation to that shocking fact. Nephrotic syndrome is a disease caused by abnormality in the kidney mainly the glomeruli in the nephron; the functional unit of the kidney. It leads to many endless complications such as oedema and hypertension. One of the ways to treat it is steroids. Although it is a magical drug but it stabs us in the back. We can take the risk and treat the patient with steroids but it gives no effect. That’s due to mutation variation between different patients.

Going back to cancer, if one of the family members previously had cancer, it might be, with considerable percentage that it’ll be inherited to another family member. This also ensures the importance of studying our genes and how they “change”.

Not all mutations are that terrible. “If it weren’t for some mutations, we wouldn’t have survived”. One of my very respectful doctors told us that. I simply wouldn’t be writing you this post and you wouldn’t be reading it. There is no absolute. Everything has its good and bad side. The clever is who use the good and take care of the bad.



Comments 1 Comment »

I have to admit that it is pretty odd “or at least for me” to learn the countless aspects of life itself that we, as human beings, share with primitive organsims “as in bacteria”…& yet add another to the growing pile: The Concept of Hand-in-Hand

Helmholtz Centre for Infection Research

Rarely do bacteria grow as single cells, they rather prefer to grow as colonies which adhere to all kinds of surfaces forming “biofilms“. These biofilms have proved to be pretty effective in maintaining the well-being of the bacteria growing within them and needless to say, this possess a serious threat. Nothing seems to work with them, ranging from disinfectants and antibiotics all the way to our very own immune system.

Scientists, now, have identified a mechanism which is thought to be used by the bacteria, within the biofilm, to protect themselves. Pushing star wars aside, these biofilm bacteria are using chemical weapons as their defense.

Taking a model for this study, researchers compared marine bacteria getting attacked by amoebae to these biofilm bacteria getting attacked by phagocytes.

To take a closer look, these bacteria are easily attacked when they are swimming separately in the water, but once they are attached to a surface, the amoebae can no longer harm them. Not only that, but the amoebae were sometimes de-activated or even killed. A classic example of FIGHTING BACK!!
How do they do it?? Through chemical weapons.

Marine bacteria contain the pigment violacein. If the enemy attacks just a single cell, the pigment is released paralyzing and triggering a suicide mechanism in the amoebae.

Amoebae are thought to be the ancestors of some types of pathogens. So, instead of thinking of biofilms as a problem, they may be source of highly effective agents which can only be produced in a biofilm and can help us fight aganist some of these pathogens.

After all, it IS a small world

Tags: , ,

Comments 2 Comments »