Wednesday, 7 December 2011

Updating.......



Newbies:
"PfRh5"- a protein on the parasite Plasmodium falciparum which is necessary for the parasite to identify its target and invade.


ARHGEF3- important new regulatory  gene for  the uptake of iron which affects platelets population  from the largest genome wide study involving about 68,000 individuals from different ancestries (European, South & East Asian).
New Confusing Words:
Genetic sub-functionalization- Ancient genes split into pairs that separately control complementary forms of symbiosis (nodulation and mycorrhization) in Legumes
New AGCTsss:
SC2.0 PROJECT- Synthesis of the whole yeast genome that has been completed in two chromosome arms, 9R and 6L.

FoldIt


We have more than 100,000 types of protein in our bodies alone. Though the primary structure of the proteins can be easily deduced (both by sequencing and using the genetic code) the functional three-dimensional structure prediction arising from folding —is more computationally demanding. There are many diseases caused by misfolding of protein are aplenty- cystic fibrosis (misfolded CFTR protein), Marfan syndrome (misfolded fibrillin), Fabry disease (misfolded alpha galactosidase). They may also be the reason for some cancers due to ineffective functioning, of tumour suppressor proteins such as von Hippel Lindau protein or p53.
Thus it is almost impossible for the scientific community which is small relative to the growing number of population and the fatal diseases to find a solution for this.

Recently thanks to cyberspace the key to unlock the innumerable cures to the vast diseases maybe found by a 13 year old video gamer who has never heard of whatsoever never heard of protein steric hindrances or anything about protein folding.

WHAT???

Everybody wants to have high scores in the games they play. And also humans have puzzle-solving intuitions that are absent in computers .FoldIt an online puzzle video game about protein folding exploits these aspects. Here the gamers analyse the problem of proteins, theirs structures, folding as game.

Stage 1:

Download FoldIt (free).
Read the rules.
Warm yourself up through a series of tutorials in which simple protein-like structures based on real proteins are manipulated with the aid of a set of tools

Stage 2:
Manipulate amino acid chains starting simple with "One Small Clash," through "Rubber Band Reversal. The application displays a graphical representation of the protein's structure. The objective is to fold the structure of proteins . When the energy required  in maintaining the molecule in a particular shape drops it is closer to original protein structure. This increases the player’s score increases.
Stage 3:
The Real Deal- Facing the unknown Demon.
A problem based on proteins whose folding and 3D structures are yet unknown is posed on the website and thousands of players compete to see who can find the best solution. There is fierce competition to see who could come up with the best solution (based on how well the different structural pieces of the protein fit together).  The highest scoring solutions are analysed by researchers, who determine whether or not such a native structural configuration exists.
Thus by analysing different” high scored” models generated by the gamers the scientists may actually find the real model.


High Scorers:
FoldIt helped to decipher the crystal structure of the Mason-Pfizer monkey virus (M-PMV) retroviralprotease, an AIDS-causing monkey virus. This is a key enzyme in the production of a mature virus and so developing drugs using this structure could be useful in developing an HIV therapy. The interpretation of the x-ray data of the protein to give the final 3D structure could not be done. FoldIt players (FoldIt Contenders Group and FoldIt Void Crushers Group, spvincent, grabhorn, mimi) optimized the 3D model, based on an NMR structure in just ten days.  The top groups were listed as co-authors by their team name in the publication (This was a problem which had frustrated scientists for 15 years. But FoldIt game has solved it in 10 days)
There are tools for players to encode their folding strategies as “recipes” and to share their recipes with other players, who are able to further modify and redistribute them. Through this Players developed over 5,400 different recipes. The most successful recipes rapidly spread through the FoldIt player population, and two of the recipes became particularly dominant. Examination of these two recipes revealed a striking similarity to an unpublished algorithm developed by scientists over the same period.
The FoldIt Void Crushers group improved a structure generated by the Rosetta Server to generate a near-native conformation of Pseudomonas aeruginosa protein T0581
FoldIt has four publications and a host of puzzles left to solve from deadly diseases to bio fuels, FoldIt has proven that the concept, "creativity isn't constrained by what they think a correct answer should look like” Thus the creative nature of individuals with no academic background on biochemistry has helped in unlocking the problems on biomoleucles

New Games:

EteRNA- folding of RNA molecules for designing RNA based nanomachines (more on NanoDNA and NanoRNA in my following blog entries)

Phylo - determine the most likely nucleotide sequence of each species by comparing the sequences of children species with those of a most recent common ancestor.

Let Genes Define who you are


Scenario:
To be or not to be is the question.
Should I head off to the race track?
Should I head off to the aerobics room?
Should I just sleep in the room because stretching a few muscles never makes any difference? Nor is it going to turn me into an athlete. But still there are stories of people who have started training late yet have made it to the top? Could I be one of the cases?
Or maybe no amount of training from the time I was born could change me? Even though both of my parents have a showcase full of trophies?
Oh! What should I do? What should I be?
Now our genes will help in clearing our dilemma. No one could have thought that a single nucleotide change could make the difference between the lanky clumsy kid who always finishes last and the cool kid who dashes through the 100 meter line easily without sweat.
WHAT?????
We all use fast muscle fibres for games which require maximum force and quick action such as running, skiing, and volleyball. Alpha-actinin 3 protein is present mostly in these fibres. This protein contributes to the muscle's ability to generate forceful, repetitive muscle contraction. It is encoded by ACTN3 gene
There may be R577X polymorphism in the ACTN3 gene which results in α-actinin-3 protein deficiency. But as can be seen this protein is essential for sprinting. So sprinters mostly have a genotype where in this polymorphism is absent. Almost all of the Olympic runners are of this type . Hence if you also have the full functional production of actinin 3 protein you may share the genetic composition as the Olympic players.
Alternative: In case you are really not interested in having your Cheek Swabs tested for this sports gene by personal genomics companies 23andMe and deCODEme, there is always the “Digit Ratio Theory”
 Hold your hand, palm up. Measure the lengths of your index finger and your ring finger. Divide the former by the latter. If the ratio is closer to .90 than 1.0, you may be a sport star with the likely genotype of R.

The amount of a foetus' exposure to testosterone in the womb determines the length of the ring finger, while estrogens levels are expressed in the length of the index finger. More testosterone means more physical ability which could imply your destiny to be a sprinter.
Warning:
Of course having the ratio of .90 or RR genotype does not necessarily mean you are automatically qualified for Olympics. The genes are additive and not exclusive. You need to have training along with genetic testing if you consider sprinting seriously.


Other tests for people who might have “failed “in this sports genetic testing:
COMT gene- Mutations results in better working memory and higher verbal reasoning.
SNAP-25 – The SNPs in this decides whether you have the higher or lower IQ value.

How to turn a negative into positive

For this question there are many kind of answers ranging from the quirky dry humour of drawing a straight line through the minus sign to other philosophical answers of finding your one true self.... etc.
Now Fat (Stem Cells) Auto graft Muscle Injection (FAMI) or simply structural fat grafting   provide another type of answer to that.
Here the negative point being the fat cells.
The fat cells have long been proven as beneficial. They are a store house of  energy in the form of lipids, a major endocrine organ producing  hormones such as leptin, resistin, and one of the combatants of  viral attacks through cytokine TNFα production.
Yet no one could really coax their way out of being obese by citing these reasons. Liposuctions have done their best to alleviate the problems face by this obese population. But now FAMI have taken this a step further. This approach uses the stem cells obtained from fat cells for facelift and other plastic surgeries.
Grafting turns the negative fat cells to a positive through 7 steps.
1.      Liposuction collects excess fat from the patient such as stomach or thighs.
2.      Fat cells are separated from the stem cells. The yield being ten times more than in bone marrow
3.      The stem cells are concentrated.
4.      The cells are activated using low-level laser.
5.      The stem cell-enriched fat are then injected into the strategic locations in face in small amounts (less than 0.1 cc at a time) in a series of discrete layers to gradually 'build' new soft tissue structure.
6.      The injected stem cells could rejuvenate the skin with new collagen and blood vessels.
7.      The wrinkles flatten, the pores become smaller, and the colour of the skin is more even and usually lighter.
TaDa. The bloated belly has given way to a fuller, younger-looking face a more natural, youthful look than traditional face-lifts.
Now the added positive that have come out of this negative:
 It is a safe, non surgical permanent and natural approach to face lifts, compared to Injectable fillers, such as Restylan used in plastic surgery.
The elimination of the need for future "maintenance" injections due to survival of a substantial amount of the injected fat.
For therapeutic purposes such as the repair of chronic wounds, the restoration of heart tissue after a heart attack, the recovery of skin damaged from exposure to the sun's radiation.
Now the icing on this cake of positives-  Indiana-based engineering and life sciences companies have contracted with researchers at the University of Pittsburgh to adapt this technology to help soldiers regrow tissue and recover from severe wounds by their fat.