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Name: Noble Prize Winners: Faizan Malik Wikins, Watson and Crick. Question: 1). Wikins, Watson and Crick are given Noble Prize for what discovery? (structure of DNA only) 2.) Describe each one’s contribution towards the discovery? 3.) What was known before (about the discovery) 4.) The impact on advancement of science: what was known before the discovery and the impact on science after the discovery. -----------------------------------------------------------------------------------------------------------Discovery of DNA structure Introduction: During the first half of the twentieth century, proteins were considered carriers of hereditary information. In the 1920s, Fred Griffith demonstrated that bacteria are capable of passing on genetic material through a process known as transformation. Oswald Avery, Colin MacLeod, and Maclyn McCarty conducted experiments to identify the transformation factor and claimed that DNA contained hereditary information. However, their claims were met with reluctance within the scientific community. Some argued that the experiments were poorly conducted and must have been exposed to contamination. At the time, one of the biggest mysteries in medical science was regarding genetic information: how it is held inside an organism and how it passed on to next generation? It was only in 1953 that the legendary scientists, James Watson and Francis Crick, discovered structure of DNA and confirmed its ability to pass on genetic information. Name: Noble Prize Winners: Faizan Malik Wikins, Watson and Crick. Methodology: Deciphering the sequence: During the 1940’s, while the scientific community knew that the molecule of life was DNA, many scientists considered this idea rather “simplistic”. By then, Erwin Chagraff had discovered that DNA consisted of base pairing molecules adenine (A), guanine (G), cytosine (C) and thymine (T), where A paired with T and G paired with C (known as Chagraff’s rule). However, the main question still remained: what is the structure of DNA? Rosalin Franklin and Maurice Wilkins conducted the first series of experiments to discover the structure of DNA. They used X-ray diffraction studies to elucidate DNA conformation. The X-ray diffraction technique involved shining an X-ray beam onto a crystal containing biological material. When the X-ray hits the crystal, the scattered beams are caught on a photographic film. When analyzed, the pattern provides insight into the molecular structure. Using information of the Chagraff’s rule and Rolind Franklin’s X-ray diffraction structure, Watson and Crick first theorized that DNA was a triple helix. However, upon later discovering the semi-conservative nature of DNA, they modified their structure to a double helix. In their paper published in 1953, Watson and Crick suggest that each strand of the double helix acts as a template for a new strand during DNA replication. DNA replication is the process in which DNA makes a copy of itself before division. For example, in humans, each parent cell must copy its entire six billion base pairs of DNA before undergoing mitosis. But there was no way of knowing how the Name: Noble Prize Winners: Faizan Malik Wikins, Watson and Crick. parent strands combine with the daughter strands to form double helical DNA. Thus there were three potential methods of replication: conservative, semi-conservative and dispersive. Conservative replication is where the the two parent DNA strands stay together in a double helix and produce a new DNA copy composed of two daughter strands. Semi-conservative replication, on the other hand, is where after replication each DNA strand consists of one parent strand and one daughter strand. Dispersive replication, on the other hand, is where two copies of DNA are produced, containing distinct regions of DNA composed of either both parent strands or both daughter strands. Of the three types of replication, the semiconservative model seemed most reasonable, as it would allow each daughter strand to remain associated with its template strand. Therefore along with the structure of DNA, Watson and Crick hypothesized that the mode of DNA replication was semi-conservative. This model was later confirmed by the Meselson-Stahl experiment. In their experiment, Meselson and Stahl provided evidence for semiconservative replication of DNA using bacterial cells grown in medium containing 15N heavy isotope for several generations. Since DNA has a nitrogenous base, when bacterial DNA replicated, heavy N was incorporated into the DNA daughter strands. The DNA was then extracted from the cells and was separated on a salt gradient. As expected, since the bacterial cells were grown for several generation in heavy N medium, most of its DNA contained 15N, causing it to pellet out at a salt concentration of higher density. Following this, bacterial cells containing only 15N in their DNA were grow in normal media (14N). During division, the N isotope content was analyzed and compared to the densities of both 15N and 14N on a salt gradient. Following one-replication, the DNA had intermediate density indicating that conservative replication did not occur. Even after two replications, the DNA density remained intermediate, therefore ruling out the possibility of dispersive replication. Thus, the experiment proved the semi-conservative replication hypothesis. It was finally on the morning of February 28th, 1953, two men quietly made Name: Noble Prize Winners: Faizan Malik Wikins, Watson and Crick. history in the Cavendish Laboratory of Cambridge University. Along with Maurice Wilkins and Rosalind Franklin—both unsung heroes in the discovery, Watson and Crick discovered the structure of DNA and in the process, changed the face of biological science. Impact: The impact of this discovery was huge as it changed the way we see inheritance. It also set the scenario for several discoveries that would also change science forever. . Firstly, it set the cornerstone for the study of DNA replication and genetic code. Secondly, it opened the door for the surge of molecular biology and genetic engineering. Genetic engineering helps to better understand gene function and regulation. A good example is transgenic mice: “Transgenic mice contain additional foreign DNA in every cell allowing them to be used to study gene function or regulation and to model human diseases.” (Richard Twyman) Thirdly, the discovery allowed a deeper understanding of virology. Based on the experiments that were performed, we now know that DNA is the molecule responsible for carrying genetic information. We have gained a better understanding of the lifecycle of viruses and how they infect cells and this is what also led to the development of antiviral treatments. The understanding of the infection mechanism of phages on bacteria also had a huge impact on Microbiology. Fourthly, the elucidation of DNA as an information-storing molecule allowed a better understanding of mutations. It provided valuable information for the study of inherited diseases (for example, hemophilia, cystic fibrosis, ovarian cancer, breast cancer etc.). People now have access to genetic tests that determine the risk factor of genetic disorders, which helps to develop preventative care medicine.