The Fly Room at SBASSE
The quest for a deeper understanding of life at the molecular level has led biologists to use organisms like bacterium, yeast, frog, mouse, fruit fly, and thale crest plant, etc., as model systems for experimentation. Some of these organisms have been used in science for centuries and they offer an opportunity to answer research questions that are otherwise impossible to answer through experiments on humans.
Although notorious for destroying fruit crops, the fruit fly has provided insights into the biggest mysteries of the 20th century, and scientific research on it has led to six Nobel Prizes! It is worth pondering: what is so fascinating about the ‘gnat’?
The common fruit fly—Drosophila Melanogaster—has been used for biological research for over a century. Drosophila Melanogaster offers a relative mean between the most complex and most simple biological systems known to science. E. coli, the microscopic bacterium, weighs about ten-trillionth of a gram. Homosapien, the amazingly complex descendant of the primates, weighs about a hundred thousand grams. The fruit fly falls at the approximate average of the two, weighing less than two thousandth of a gram. Humans tend to have a generation time of about ten thousand days whereas E. coli has a generation time of a hundredth of a day. The fruit fly again falls in between, having the generation time of about ten days. Even the total number of genes fall at the rough average between the two extremes—Drosophila Melanogaster has about fifteen thousand genes for four thousand in a bacterium and twenty-two thousand in humans.
The real exciting fact is that nearly 60% of the fruit fly DNA is conserved in humans and about 75% of the human disease-causing genes are fully conserved in their function in the Drosophila genome, which makes the fruit fly the best model organism to work on. The similarity is shocking to the extent that some geneticists think that “they were designed to help scientists” (The Guardian).
The journey started at the start of the 20th century in the laboratory of Thomas Hunt Morgan. Morgan and his students observed different mutations in Drosophila Melanogaster which helped them prove the Chromosomal Theory of Inheritance. This showed that genes indeed lie on the chromosomes. Gene Mapping, Genetic Recombination, Sex-Linked Inheritance, and Chromosomal Nondisjunction are the major achievements of Morgan’s Lab using the fruit fly. For their remarkable discoveries, the 1933 Nobel Prize in Physiology or Medicine was for the first time awarded to a non-physician—Thomas Hunt Morgan.
After Morgan’s demise, his students took on the job of exploring the fruit fly. His student, Hermann Joseph Mueller, used X-rays to induce genetic mutations and chromosomal changes in Drosophila Melanogaster. These mutants were then studied for the functional aspects of the mutations combined with their evolutionary value. Mueller was awarded the Nobel Prize in Physiology or Medicine in 1946.
Towards the end of the 20th century, Drosophila Melanogaster once again solved the mystery of development when Edward B. Lewis, Christiane Nüsslein-Volhard, and Eric F. Wieschaus used the fly embryo to understand the genetic control of development. This led the trio to win the Nobel Prize in Physiology or Medicine in 1995. Key developmental genes discovered in flies responsible for body axis formation and patterning are astonishingly conserved in humans and other vertebrates.
In the middle of the 20th century, Seymour Benzer at Caltech started using Drosophila Melanogaster to understand another mystery in biology—the atomic theory of behaviour.
He was interested in knowing about the ‘atoms’ of behaviour. Several behaviour genes were discovered in the fruit fly and it was the very first time when behavioural phenotype was proved to be due to the presence of specific genes in the genome. Benzer did not live to see the success of his work, but the ground-breaking work on the fruit fly circadian rhythm (sleep genes) by his postdoctoral fellows, Jeff Hall along with Michael Rosbash and Michael Young went on to win the Nobel Prize in Physiology or Medicine in 2017.
The Fly Room at SBASSE was started in 2009 when Dr. Muhammad Tariq, founding chair and associate professor at SBASSE, returned to Pakistan to establish a cutting-edge epigenetics research programme. The Fly Room at LUMS is the first and, so far, the only fruit fly lab in Pakistan and it is an integral part of learning fundamental concepts of genetics, developmental biology, molecular biology, and epigenetics at undergraduate and postgraduate levels. Through specifically designed experiments for both undergraduates and graduates, students visually observe giant larval chromosomes, proteins associated with chromosomes, activation of genes in response to heat shock, and much more.
In the beginning, rearing flies at LUMS was a massive challenge due to largescale deaths of precious fly stocks because of fluctuating electricity issues and the breakdown of incubators in extreme heat. However, presently the Fly Room houses nearly five hundred different fly stocks, each of which is maintained in multiple vials to minimize the risk of loss of a specific fly stock due to the accidental death of these flies. Due to extremely high temperatures, flies related to various ongoing experimental research projects as well as for teaching laboratories are ordered only during winter times from the Bloomington Drosophila Stock Centre in Indiana, USA. As soon as these flies arrive, they pass through quarantine and then they are bred on specialised corn-starch food prepared in the biology department. Besides a walk-in incubator there are two refrigerated incubators maintained at 18˚C and 25˚C for maintaining stocks and experimentation, respectively.
The Fly Room is a busy place where students and researchers are either setting up fly crosses or analyzing results of their crosses by sitting long hours on stereo microscopes. Since setting up an experimental cross requires identifying female virgin flies as well as young males, it demands all researchers be extremely organised and available seven days a week. Moreover, the Fly Room also houses a microinjection facility which is used to inject freshly hatched embryos to generate transgenic flies required to understand the genetic and epigenetic basis of genes being probed by the Tariq Lab at LUMS. The Tariq Lab focuses on understanding how the identity of different cell types is maintained and how cell fates can be changed.
Answers to these fundamental questions have implications in the field of cancer and regenerative medicine. Genetic and molecular analysis has discovered two groups of genes known as the Polycomb group (silencers) and Trithorax group (activators) which are responsible for the maintenance of cell fates. The Fly Room aims to understand how activities of Polycomb group or Trithorax group can be modulated and consequent cell fates changed.
To honour the renowned tale of the fruit fly research and its contribution to understanding some of the major questions related to humans, the Drosophilists at the SBASSE call the Fly Room, the Morgan Room, in the loving memory of Thomas Hunt Morgan who was the pioneer of Drosophila research.
The fruit fly still has wonders to reveal…
Muhammad Abdullah Jauhar is a Biology Junior and member of the Epigenetics group (Tariq Lab) who coordinates all seminars of the MCB series.