Interdisciplinary research – Nobel Prize for Chemistry was awarded to two Biologists

Modern scientific research does not confine itself to any restricted boundary.  Nowadays, it is all about interdisciplinary research. In 2012, Nobel Prize for Chemistry (http://www.nobelprize.org/nobel_prizes/chemistry/)was awarded to two eminent biologists, Prof. Robert J Lefkowitz and Prof. Brian Kobika, for their crucial contribution in unveiling the signalling mechanism of G protein-coupled receptors (GPCRs). It’s a lifetime work of both the scientists. Dr. Lefkowitz, an investigator at Howard Hughes Medical Institute (HHMI) at Duke University, is also James B Duke Professor of Medicine and of Biochemistry at Duke University Medical Center, Durham, NC, USA. Dr. Kobika, earlier a postdoctoral fellow in Dr. Lefkowitz’s laboratory, is currently Professor of Molecular and Cellular Physiology at Stanford University, School of Medicine, Stanford, CA, USA.

Transmembrane signalling of one GPCR “caught in action” by X-ray crystallography

GTP (guanosine triphosphate) binding proteins (G-protein) act as molecular switches in transmitting signals from different stimuli outside the cell to inside the cell. However, for doing this G-protein needs to be activated, and that is where GPCRs play the most important role. They sit in the cell membranes throughout the body. GPCRs, also known as seven transmembrane (pass through the cell membrane seven times) domain proteins, detect the external signals like odor, light, flavor as well as the signals within the body such as hormones, neurotransmitter.1 Once the GPCRs detect a signal, the signal is transduced in certain pathway and finally activate the G-protein. In response, the activated G-protein triggers different cellular processes. Binding of a signalling molecule or ligand to the GPCR causes conformational changes in the GPCR structure. As a result of extensive research of 20 long years, Dr. Lefkowitz and Dr. Kobika not only identified 800 members of GPCRs family in human but also caught in action how these receptor proteins actually carry out the signal transduction with the help of high resolution X-ray crystallography. The crystal structure of ß2-adrenergic receptor (ß2AR), a member of the human GPCRs family was reported by Dr. Kobika and his colleagues in 2007.2 The hormones adrenaline and noradrenaline are known to activate ß2AR, and the activated ß2AR triggers different biochemical processes which help in speeding up the heart and opening airways as body’s fight response. The ß2AR is a key ingredient in anti-asthma drugs. One of the major breakthroughs came in 2011 when Dr. Kobika and his co-workers unveiled for the first time the exact moment of the transmembrane signalling by a GPCR. They reported the crystal structure of “the active state ternary complex composed of agonist-occupied monomeric ß2AR and nucleotide-free Gs heterotrimer”.3 A major conformational change in ß2AR during signal transduction was discovered.

Now what is so special about GPCRs? Well, these proteins belong to one of the largest families of  all human proteins. GPCRs are involved in most of the physiological activities, and hence are  the targets of a number of drugs. Determination of the molecular structures of this class of receptors not only helps the researchers to understand the actual mechanism of different cellular processes but also help them to design life saving and more effective drugs. So, in a nut shell, this scientific breakthrough was possible due to the involvement of experts of different areas of science such as, chemistry, biochemistry, molecular and cellular biology, structural biology, cardiology, crystallography.

 

References

 

  1. Lefkowitz, R. J. Seven transmembrane receptors: something old, something new. Acta Physiol. (Oxf.) 190, 9–19 (2007).
  2. Rasmussen, S. G. et al. Crystal structure of the human b2 adrenergic G-protein coupled receptor. Nature 450, 383–387 (2007).
  3. Rasmussen, S. G. et al.  Crystal structure of the b2 adrenergic receptor–Gs protein complex. Nature 477,  549-557 (2011)

 

The Writing Process

The Internet

The internet has emerged as the best source of information. There is practically nothing that you cannot find by browsing the internet. Think about any topic science, technology, medicine, engineering, sports, jobs, education, etc.  the internet has it all.

But, the information provided in the Internet differs in its accuracy, reliability, and value. There are lots of choices, but one cannot be sure if the data they are reading is accurate or not. Some sources may even be outdated and unverifiable. Unlike the conventional information sources (books, magazines, official documents, etc.), information posted in the internet does not require to be approved before it is made public.

When writing research papers, the researcher needs to evaluate the sources. He needs to make decisions about what to search, where to search, and once the relevant material is found, has to check whether it is a valid. The researcher faces difficulties in assessing the credibility of information, and it is extremely time consuming. At times, it can be frustrating. There is a vast amount of information at your disposal, but you may not find exactly what you need.

Sources of Information on the Web

Websites: Much of the information on the internet is available through websites. They vary widely in the quality of information and validity of sources that they provide.

Weblogs/Blogs: These are quite recent development in web technology. These online forums facilitate discussion and collaboration. Here, the writers post something and the readers respond to it. Blogs of prestigious journalists and public figures are more credible than other blogs.

Message boards, discussion lists, and chat rooms: These exist for all kinds of disciplines, more particularly, for universities.

Multimedia: The Internet has a huge amount of multimedia resources, which includes online broadcasts, news, images, audio files, and other interactive websites.

Categories of Information on the Web

The Free, Visible Web: It includes all the publicly mounted web pages, which are indexed by search engines. You can use a good search engine or directory to find information from this category.

The Free, Invisible Web: It includes the websites that provide their articles or information free to users. But, this information can be obtained only by going directly to their home page; search engines cannot index it. Ex.: magazines, newspapers, reference works, etc. Legal, medical, and financial databases can also be included in this category.

Paid Databases: It includes commercial databases containing scholarly journals, newspapers, court cases, etc. You need a password/or have to be a subscriber/or be a member, etc. to obtain information from this category.

Types of Search Tools

Search Engines: A search engine consists of an interface to key a query, an index of Web sites that the query is matched with, and a software program (called a spider or bot) that goes out on the Web and gets new sites for the index. Many search engines are now becoming reference sites, which provide much more than just search capability. They also have news, weather, free software, picture indexes, ratings of web sites, etc. Ex.: Google, Fast Search, Northern Light, HotBot, AltaVista, Britannica, Bartleby, etc.

Directories: Directories are an organized collection of links to websites picked out by human editors. These are much smaller than search engines. But, the credibility of the articles and sites it provides is very high. Ex.: Yahoo, Look Smart, Snap, etc.