Prize+Winning+Research



"** Can you believe that some people have dedicated their life's work to little ol' me?!" **

In 1995, in Stockholm, Sweden, 3 scientists were awarded the Nobel Prize in Medicine for pioneering research into genetics and its control over embryonic development, by identifying and classifying the genes which control the development of the Drosophila Melanoggaster fruit fly. This has involved 50 years of research into homeotic transformations (the type of mutations and malformations exhibited in the fruit fly, whereby cells in one region act as though they are located in another area). This research was aimed at improving our understanding of factors affecting human embryology and birth defections, as these genes are thought to account for about 40% of congenital malformations. The Drosophila fruit fly is now known as a "standard model" in genetic research, as it shows rapid development from a fertilised egg to an embryo in just nine days, and because the results of the research can be applied to higher organisms, namely humans and animals. Moreover, it has subsequently been found that analogous genes in the fruit fly exist in the human body.

The research was based on previously known information that the fertilised (spherical) egg divides rapidly to form 2,4,8,16 cells; beyond this division, cells begin to specialise and the embryo is no longer symmetrical. The embryo develops into distinct head and tail, ventral and dorsal regions within a week. This natural phenomenon prompted a lot of scientific questions, such as: which genes are involved in this process? How do they exert their effects? Do they operate independently or collaborate?

Dr. Edward Lewis of the California Institute of Technology, was the elder of the three scientists at 77 years of age to shed some light on some of this uncertainty. He was the first to explore the influence of genes in the development of individual body segments into specialised organs, finding that the genes on chromosomes are infact arranged in the same order as the body segments they control. His work involved exploring the reason that an extra pair of wings observed in a natural mutation of Drosophila was the result of a duplication of an entire body segment. His research concluded that the halteres (balancing organ of the fly), which is normally produced by the first gene of the bithorax complex in the segment, was missing due to inactivity of this gene. Consequently, in an attempt to provide the fly with an element for balance, other homeotic genes respecialised the next segment into one that forms wings, rendering a 4-winged Drosophila fruit fly. During this time, his theory also led to the conclusion that genes at the beginning of the complex controlled the anterior body segments, while genes further down the body-tail axis controlled posterior body segments; the **__Principle of Colinearity__**.

In 1978, he summarised his conclusions and theories about how homeotic genes interact, the order of genes and their corresponding body segment, and how individual genes are expressed. This prompted other scientists to study analogous genes in higher organisms, leading to the discovery of the duplication of the gene cluster found in the Drosophila into four complexes known as the __HOX genes__. The individual genes occur in the same order as in the Drosophila, and have the capacity to restore some of normal Drosophila gene function. Disruption to HOX gene regulation, coupled with environmental factors such as high doses of Vitamin A during pregnancy, can result in severe congenital malformations.

Dr. Christiane Nuesslein-Volhard of Germany's Max-Planck Institute and Dr. Eric Wieschaus of Princeton University finished their scientific training towards the end of the seventies, and were subsequently offered independent research positions at the European Molecular Biology Laboratory in Heidelberg. Incidently, they already shared a common interest in the Drosophila fruit fly and how the fertilised egg develops into a segmented embryo. They followed Lewis' work and collaborated in an effort to identify the genes responsible for this development. The carried out a process of treating flies with a mutagenic substance, thereby manipulating half of the Drosophila genes randomly and examining genetic crosses of mutant Drosophila strains. Following this, they examined which genes, if mutated, would alter development either the pattern or formation of body segments. They were able to analyze and classify 15 malformations caused by mutations of the genes responsibly for early embryonic development based on their order of importance in embryonic development as well as their effects of segmentation. Some of the genes identified were: -Gap Genes: genes that control the body 'plan' along the head-tail axis, whereby loss of function results in less body segments. The research of Nuesslein-Volhard and Wieschaus was published in the __**English Scientific Journal**__ **__Nature__ in 1980, establishing the principle that **developmental genes can be systematically identified and classifies into specific functional groups.
 * Pair Rule Genes: These genes affect every second body segment, and absense of the "even-skipped" gene results in an odd number of body segments.
 * Segment Polarity Genes: These genes influence the head to tail polarity of individual segments within an embryo.The genes being examined function in body segmentation, embryo polarity and the subsequent specialisation of these segments into different organs.

This remarkable work will hopefully further research into the development and treatment of gene mutations and therefore rare genetic diseases:
 * Waardenburg's Syndrome, which is a paired human gene related to the Drosophila gene, and is a rare disease involving deafness, defects in the facial skeleton and altered iris pigmentation.
 * Aniridia is a gene mutation which is characterised by complete loss of the iris.

This research into genes and their complex functions in the body is one case of an ever-expanding field of Medicine, and has served as a legacy to understanding the control exerted by genes in the body, their interactions, and will hopefully serve as a basis for future research and disease prevention. Content from:
 * http://www.acessexcellence.org/WN/SUA06/aenobmed.php