Critical Analysis of Classical Papers

CONTENTS

Students may be divided in groups and each group may be responsible for one classical paper. Each week there may be a 1.5hour presentation cum discussion for each of the papers. At the end of the semester each student will be asked to write a mini-review (2-3 pages long) on any one classical paper, other than the one he/she presented/discussed

A list of sixteen classic papers and some suggested reference materials:

Molecular Biology

1.Studies on the chemical nature of the substance inducing transformation of Pneumococcal types: Induction of transformation by a desoxyribonucleic acid fraction isolated from Pneumococcus type III.

Avery OT, Macleod CM, McCarty M.; J Exp Med. 1944 Feb 1;79(2):137-58.

Note: This paper demonstrates that DNA is the transforming Principle originally described by Fredrick Griffith.

2. Independent functions of viral protein and nucleic acid in growth of bacteriophage

Hershey AD and Chase M.; J Gen Physiol. 1952 May;36(1):39-56.

Note: This paper demonstrates that DNA, and not protein, component of phages enters bacterial cells.

3. Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid

Watson JD and Crick FH; Nature. 1953 Apr 25;171(4356):737-8

Note: In this one page paper Watson and Crick first described the structure of DNA double helix Study help - Watson_Crick_Nature_1953_annotated

4. Transposable mating type genes in Saccharomyces cerevisiae

James Hicks, Jeffrey N. Strathern & Amar J.S. Klar; Nature 282, 478-483,1979

Note: This paper provided evidence for ‘cassette hypothesis’ of yeast mating type switches i.e. interconversion of mating types in yeast (S. cerevisiae) occurs by DNA rearrangement.

5. Messelson & Stahl experiment demonstrating semi-conservative replication of DNA.

Meselson M and Stahl FW.; Proc Natl Acad Sci U S A. 1958 Jul 15;44(7):671-82

Note: The experiment demonstrating semi-conservative mode of DNA replication is referred to as "the most beautiful experiment in biology"

6. In vivo alteration of telomere sequences and senescence caused by mutated Tetrahymena telomerase RNAs. Guo-Liang Yu, John D. Bradley, Laura D. Attardi & Elizabeth H. Blackburn; Nature 344, 126-132, 1990

Note: This paper demonstrates that the telomerase contains the template for telomere synthesis

Cell Biology

1. A protein-conducting channel in the endoplasmic reticulum

 Simon SM AND Blobel G.; Cell. 1991 May 3;65(3):371-80

 Note: This paper demonstrates the existence of a protein conducting channel

 Study help - A brief history of Signal Hypothesis

2. Identification of 23 complementation groups required for post-translational events

 in the yeast secretory pathway

 Novick P, Field C, Schekman R.; Cell. 1980 Aug;21(1):205-15

 Note: In this groundbreaking paper Randy Schekman's group used a mutagenesis

 screen for fast sedimenting yeast mutants to identify genes involved in cell secretion

3. A yeast mutant defective at an early stage in import of secretory protein precursors

 into the endoplasmic reticulum

 Deshaies RJ and Schekman R.; J Cell Biol. 1987 Aug;105(2):633-45

 Note: Using another yeast mutation screen Schekman lab identifies Sec61, a

 component of ER protein Conducting Channel (PCC)

4. Reconstitution of the Transport of Protein between Successive Compartments

 of the Golgi

 Balch WE, Dunphy WG, Braell WA, Rothman JE.; Cell. 1984 Dec;39(2 Pt 1):405-16

 Note: This paper describes setting up of an in vitro reconstituted system for

 transport between golgi stacks which eventually paved the way for identification of

 most of the molecular players involved in these steps including NSF, SNAP etc.

5. A complete immunoglobulin gene is created by somatic recombination

 Brack C, Hirama M, Lenhard-Schuller R, Tonegawa S.; Cell. 1978 Sep;15(1):1-14

 Note: This study demonstrates DNA level molecular details of somatic

 rearrangement of immunoglobulin gene sequences leading to the generation of

 functionally competent antibody generating gene following recombination.

6. A novel multigene family may encode odorant receptors: a molecular basis for

 odor recognition

 Buck L and Axel R; Cell. 1991 Apr 5;65(1):175-87

 Note: This paper suggests that different chemical odorants associate with different

 cell-specific expression of a transmembrane receptor in Drosophila olfactory

 epithelium where a large family of odorat receptors is expressed.

7. Kinesin walks hand-over-hand

 Yildiz A, Tomishige M, Vale RD, Selvin PR.; Science. 2004 Jan 30;303(5658):676-8

 Note: This paper shows that kinesin motor works as a two-headed dimeric motor

 walking hand-over-hand rather than like an inchworm on microtubule tract using the energy of ATP hydrolysis

Developmental Biology/ Genetics

1. Mutations affecting segment number and polarity in Drosophila

 Christiane Nusslein-Volhard and Eric Weischaus; Nature 287, 795-801, 1980

 Note: This single mutagenesis screen identified majority of the developmentally

 important genes not only in flies but in other metazoans as well.

2. Information for the dorsal--ventral pattern of the Drosophila embryo is stored

 as maternal mRNA

 Anderson KV and Nüsslein-Volhard C; Nature. 1984 Sep 20-26;311(5983):223-7

 Note: This landmark paper demonstrated that early dorsal-ventral pattern

 information is stored as maternal mRNA in flies and devised the method of

 identifying genes encoding such genes

3. Hedgehog signalling in the mouse requires intraflagellar transport proteins

 Huangfu D, Liu A, Rakeman AS, Murcia NS, Niswander L, Anderson KV.;

 Nature. 2003 Nov 6;426(6962):83-7

 Note: One of the architects of original fly mutagenesis screens conducted a mouse

 mutagenes screen which identified a gene Kif3a as a major component of hedgehog

 signaling pathway. Eventually this discovery revolutionizes our understanding of

 mechanisms of action of signaling pathways by demonstrating central role of

 cillia in it.

 Suggested Reference paper - Design and execution of a embryonic lethal mutation

 screen in mouse.