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)

 

Peer Review Mechanism

Many of us have often come across the terms “peer review”, “peer-reviewed journal” or “peer-reviewed paper” at some or the other point of time. But, how many of us know what exactly the term “peer review” refers to or what the “peer review process” is all about? Let us discuss this key aspect of the research process.

According to the International Committee of Medical Journal Editors (ICMJE), peer review is the critical assessment of manuscripts submitted to journals by experts who are not part of the editorial staff. Peer review, which is also known as refereeing, has become an inevitable part of the quality control process, which determines whether a paper is worth publishing/funding or not.

The origin of peer review often dates back to 18th century Britain. However, it became a key part of the research process only in the second half of the 20th century, triggered by the growth of scholarly research. As the reviewers are specialized in the same field as the author, they are considered to be the author’s peers; hence, it was coined as “peer review”.

Peer Review Process

The author submits the paper to the respective journal. The Journal Editor forwards that paper to experts (reviewers) in the relevant field. These reviewers thoroughly analyze the quality of the paper, validity of the data and methods used, and the accuracy of the results. They provide their judgment on the paper whether: there is scope for improvement, it is ok as it is, or it is not worth publishing. If there are changes to be made in the paper, the reviewers list in their comments the particular areas that have scope for improvement. Then the paper is returned to the Journal Editor who sends it to the author with the appropriate decision: accepted as it is; accepted with revisions; or rejected. Accordingly, the author makes the changes and resubmits to the same journal, or resubmits to another journal.

Types of Peer Review

Peer review can be classified into three types based on the levels of transparency:

Single-blind review: In this case, the author’s identity is known to the reviewers, but not vice versa.

Double-blind review: In this case, the identities of the author and reviewers are hidden from each other.

Open peer review: Here, the author’s and reviewers’ identities are known to each other.

At present, the peer review process is implemented by a majority of scientific journals. It helps to prevent falsified work from being published. Its importance has become such that, most research are not considered to be serious stuff unless they have been validated by peer review. A peer-reviewed paper that is accepted for publication is looked upon as a work of quality. But, this process has its own disadvantages. It is an extremely time-consuming process. The long wait can be extremely frustrating for the researcher and can even jeopardize his academic progress. Moreover, sometimes the element of bias creeps into the peer review process. The reviewers’ judgment might be influenced by their own perception of things, the identity of the author, and at times, even the country of origin of the author.

Factors of Audience Analysis

Psychographics

Psychographics refers to the lifestyle, values, leisure activities and social self-image that the readers are likely to have. Marketing research shows that people react favorably towards products and services that they see as representative of themselves. Similarly, your readers will respond differently to your message according to their values. What are their interests, opinions and hobbies’? In the rapidly changing and diversifying contemporary world, interests and values are less and less tied to demographic issues. For example, when computer games first started to develop, they were associated with a target market of young males in the 15 to 25 age group. As this form of entertainment evolved, the target market changed, and there are now computer games that attract females, older males, and other demographic groups. An analysis of the computer game market, therefore, is more likely to benefit from a psychographic examination that would see the computer game market as a special interest group, rather than a demographic.

Demographic and psychographic analysis are especially relevant in journalistic and public relations writing, where you address a wider public.

Audience Analysis

Every act of writing takes place in a new context, with a unique time, place or reader to take into account. Audience adaptation refers to the skill of arranging words, organizing your thoughts, and formatting your document to best achieve your desired effect on your target audience. Audience dynamics refers to the relationship that writers form with their readers through their style, and through the amount and structure of information they provide. The audience dynamics are effective when the readers get a sense of satisfaction that the questions raised in the text were relevant to their interests and the answers or solutions provided were convincing. In contrast, audience dynamics are ineffective when the readers feel frustrated or offended because the writer’s tone is condescending, the answers or solutions provided are simplistic in relation to the complexity of the questions, or the argument is emotive and based on generalization. To maximise your ability to achieve effective audience dynamics, assess the readers’ needs, knowledge and interest by conducting an audience analysis before writing. Audience analysis is an integral part of your research.