Wednesday, January 13, 2010

The Last Decade of Nobel in Physiology or Medicine

The Nobel Prize - an annual tradition which started in Sweden in the year 1901 by Sir Alfred Nobel to award the most notable achievements in Physics, Chemistry, Medicine, Literature, Peace and Economics. It is an award coveted by scientists across the board. 100 Nobels have been awarded in Physiology since 1901 to 195 individuals of which 10 are women. No Nobel in Physiology was awarded during World war I and World war II. Here I enumerate the advances in Physiology or Medicine in the last decade which have captured the Nobel.

2009 - awarded to E.H. Blackburn, C.W. Greider and J.W. Szostak "for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase".

2008 - awarded to H. zur Hausen "for his discovery of human papilloma viruses causing cervical cancer", to F.B. Sinnoussi and L. Montagnier "for their discovery of human immunodeficiency virus".

2007 - awarded to M. R. Capecchi, Sir M. J. Evans and O. Smithies "for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells".

2006 - awarded to A. Z. Fire and C. C. Mello   "for their discovery of RNA interference - gene silencing by double-stranded RNA".

2005 - awarded to B. J. Marshall and J. R. Warren "for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease".

2004 - awarded to R. Axel and L.B. Buck "for their discoveries of odorant receptors and the organization of the olfactory system".
2003 - awarded to P. C. Lauterbur and Sir P. Mansfield "for their discoveries concerning magnetic resonance imaging".

2002 - awarded to S. Brenner, H.R. Horvitz and J.E. Sulston "for their discoveries concerning 'genetic regulation of organ development and programmed cell death'".

2001 - awarded to L. H. Hartwell, T. Hunt and Sir P. M. Nurse "for their discoveries of key regulators of the cell cycle".

2000 - awarded to A. Carlsson, E. R. Kandell and P. Greengard "for their discoveries concerning signal transduction in the nervous system".

1999 - awarded to G. Blobel "for the discovery that proteins have intrinsic signals that govern their transport and localization in the cell".

Monday, January 11, 2010

From Organs to Molecules

A selection of images I captured as part of my research. The images show the transition from organs to molecules. The right most image is an echo-cardiogram of the Guinea Pig heart, middle image shows a single cardiomyocyte held by two metal needles and left most image is that of a single myofibril suspended between two 7-10 micron thin glass needles.

TED - A Beehive of Ideas

TED talks - Technology, Entertainment, Design - Ideas Worth Spreading

I stumbled upon this website and ever since my iTunes podcast has been channeled to the talks and videos on TED. TED is a unique platform where you hear the news from new frontiers of science. The talks are inspiring and educational. It is a window to new ideas and innovation. TED is a convergence of many aspects of science. The talks are wide ranging from Jane Goodalls rendezvous with the Apes to Bill Gates new ventures! While the talks give us invaluable insights into varied worlds, they leave a lot of room for exploration of these worlds and deeper understanding of these concepts. TED piques your curiosity to learn. Get those 20 minutes of inspiration today!

Ph.D. Comics - 2 min Hiatus with fellow Grads

Ever so often, all graduate students have those few minutes in the day when we wonder "Is it just me!" and that is when a comic series dedicated to our lot comes to the rescue. Back in the days of Aristotle and Plato, such luxuries were not available, but today with the prime of technology and internet connections we can glimpse into each others lives and feel consoled that "There are others like me out there. I am not alone. Phew!".  Cheers to Ph.D. comic series Piled Higher and Deeper!


A glimpse into the story of muscle

Every time we see a phenomena/object we are not conversant with, we begin by giving it a name to start conversing about it. This rule applies across the board with a very strong emphasis in sciences. Each time there is a potentially new specimen still unrecognized, a scientific name is quickly alloted to it.

Folklore has it that long time ago, in Greece, a similar story began when the budding scientists of that era noticed a mouse moving up and down the upper arm of a disc thrower every time he exhibited his skills at the sport. To begin a simple conversation they named it - muscle, a simple diminutive version of musculus meaning mouse in Latin. Thus, was launched a whole new world of muscle studies.

Thereafter, it was recognized that the organ of motion is muscle. The understanding of muscle we have now, required long nights spent in graveyards digging bodies and studying science against the beliefs of the society then. Studying the anatomy of the human body and laying the foundations of this science of contraction has traversed from graveyards to the modern day science lab with the pipette tips and the microscope. It was in 1700s that Galvani and Volta recognized that movement of charges aka biological electric currents underlie contraction and cause movement of limbs.

It was only in 1864 that Kuhne isolated a viscous protein and named it mysoin. Amidst war years and complete scientific isolation, Albert Szent Gyorgyi and his colleagues established that "myosin" consisted of two molecules of varying viscosity. In parallel, Needham et al. discovered the effect of ATP on Kuhne's myosin independently. The two groups were never able to communicate. But a molecular motor driving movement had been discovered. A century later Actin molecules were discovered by Straub in 1942. The molecular foundation of the muscle had now been laid.

In 1953, the milestone of muscle research was established by Huxley and Huxley when they proposed the Sliding Filament Theory of muscle. It was based on the observation of constancy of the length of the A-band and the shortening of the I-band during contraction. Using interference microscopy and phase contrast miscroscopy it was shown that molecular motors do not change in length while contracting but thin and thick filaments slide over one another causing the change in muscle length thereby resulting in contraction. Thus heralded a new era in muscle science.

The race to discover the regulators of contraction, the structure of these threads, the ATP utilization of this phenomena had just begun. Lymn and Taylor proposed the cross-bridge cycle in 1971, breaking down contraction in steps of ATP utilization. Tropomyosin was discovered by Bailey in 1946. That calcium removal induced relaxation was discovered by Marsh and Bendell. And to complete the jigsaw Ebashi et al. unraveled Troponins.

I embarked on this journey when I did my rotation in Dr. De Tombes lab and saw a string of sarcomeres beautifully suspended between two 7-10 micron thin glass needles. The string is called a myofibril.  The shadow of a darkly coated glass needle fell exactly in between a pair of identical photodiodes when this string did not contract. As soon as calcium hit this string, it contracted, pulled the dark glass needle and its shadow biased towards one photodiode, thereby enabling us to record the force! It exerts a force of about 50nN/mm2. To understand this beautiful wonder, I delved deep into the past origins of this story.

Justice cannot be done to this discovery of the muscle and its molecules in a short one page entry. However, one can fathom the process of scientific discovery and the eons it entails as each piece of the big puzzle falls in place. What I have written here is just a peek into this wonderful world. The work on understanding muscle is still far from complete. A new brick has to be baked everyday and molded to perfection to be laid into the wall.

Follow up Reads:

1. Prime mover by Steven Vogel
2. The Early History of the Biochemistry of Muscle Contraction - Andrew G. Szent-Gyorgyi, J. Gen Physiol. Vol 123 (2004) 631-641.