Drosophila and COVID-19

With 3.84 billion infections and 38.4 million deaths globally, this miniscule microbe has wreaked havoc. Finding information about COVID has not been easy because it is completely a new scientific pursuit. At first, finding information about this virus wasn’t easy because it emerged completely as a new entity which led to a raging epidemic affecting the whole country severely, due to its high transmission rate and severity.

So, in order to develop safe and efficacious vaccines and therapeutics to combat this deadly virus, understanding the function of the protein, its interaction with the host, and its distribution in the host was necessary for improving treatment strategies. We needed appropriate model species for this research (to address the major difficulties presented by SARS-CoV-2).

And, as always , Drosophila Melanogaster emerged as one of the promising model species for elucidating COVID-19 related problems, due to its 75% genetic similarity to humans. Providing for a robust strategy to examine the conserved action of viral proteins on host cells, necessary for a reproductive infection, their comparatively basic genetics make them very susceptible to genetic manipulation, as well.

Furthermore, the easy & inexpensive maintenance of these flies along with their rapid propagation and short lifespan assist in minimizing the time to get findings as well, which is unquestionably important during an outbreak.

The fruit fly has been successfully used in recent years to study the molecular and physiological aspects of human virus-induced pathogenic effects on host cells, including the human immunodeficiency virus (HIV), ZIKV, Dengue, West Nile, SARS-CoV-2, etc. It helps to understand host antiviral immunity and most signalling pathways are not only conserved from flies to humans but many have been identified and first studied in flies. 90% of the human proteins in the human body that interact with SARS-CoV-2 are conserved between flies and humans. It has 75% genetic similarity with humans. It is maintained easily and inexpensively in the laboratory and rapid propagation and short lifespan reduce time to obtain results.

SARS-CoV-2 genes which affected the central nervous system, life span, motor skills, etc. were studied. Proteins in multiple tissues, in this case, muscle and trachea (fly equivalent of the lung); are affected in COVID-19, moreover, it was found that there are 12 SARS-CoV-2 proteins in flies. Various metabolic risk factors such as diabetes and obesity are related to the more serious presentation of COVID-19. Flies have become a valuable model for studying human nutrition, obesity, diabetes, and metabolic diseases. These existing models can be easily used to study the risk factors of COVID-19. In addition, fruit flies have all major organs affected by COVID-19, including the heart, lungs, muscles, kidneys, blood, and brain. Mammalian models are more reminiscent of human genetics and physiology than fruit flies, but this also raises ethical issues. In addition, the larger the mammal, the longer the gestation period, and the smaller the number of offspring, the more difficult and expensive it is to study. When dealing with a virus outbreak, speed is as important as the ease of use, cost-effectiveness, and profitability of fruit flies. Many genetic tools are unparalleled. Unlike mammals, flies can carry out a large number of genetic and pharmacological studies in the body. Overall, Drosophila has a surprising advantage in the functional study of host-virus interactions, and is a powerful model system that can immediately adapt to and respond to any coronavirus attack.

References :

1.https://jbs.camden.rutgers.edu/content/respiratory-analysis-covid-19-severity-related-genes-reveals-decreased-respiration

2.https://www.researchgate.net/publication/347516066_SARS-CoV-
2_protein_ORF3a_is_pathogenic_in_Drosophila_and_causes_phenotypes_associated_with_COVID-19_post-viral_syndrome

3.https://www.frontiersin.org/articles/10.3389/fphar.2020.588561/full
4.https://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-021-00567-8

5.https://www.news-medical.net/news/20201223/Researchers-use-fruit-fly-model-to-understand-COVID-19-related-neurological-complications.aspx

By:-

Sheetal Kaur

Avneet Kaur Maan

Khushboo Singh

Shubhdeep Kaur

SGTB Khalsa College, University of Delhi

COMBAT AND CO-EVOLUTION: BATTLE FOR SURVIVAL

Predators, parasites, and pathogens all impose strong selection pressures on their hosts or prey, causing them to evolve better strategies to survive . This coevolution of pathogen virulence as well as host resistance depends on many factors, including the extent of genetic variation for traits influencing attack and defense, trade-offs between these traits and other components of fitness, and the specificity of the interaction between different genotypes in the natural enemy and in its prey or host.

Drosophila melanogaster through its peculiar interaction with wasps is a great model to study innate immunity and the co-evolving mechanisms of their survival combats.

This peculiar relationship that exists between Drosophila melanogaster (the fruit fly) and wasps is not a usual parasitic relationship but a combination of predatory and parasitic behavior – a rather lethal combination.

Because of this fundamental distinction, wasps are referred to as parasitoids, which is a feeding behavior intermediate between the parasite and predatory end of the behavioral continuum.

Wasps are parasitic only during their development phases, and adults are free-living, which is a type of parasitism known as Protelean parasitism.

The aim is to look at how Drosophila melanogaster deals with its larval endoparasitoids (e.g., Leptopilina species) and see how the combatants use different counter-strategies to protect their homeostatic mechanisms.

In these conflicts, either the hosts are consumed by the endophagous(feeding on within) juvenile stages of the parasitoid or the latter are destroyed by the host. The fate of the host depends on its ability to identify the endoparasitoid as nonself and to synthesize cytotoxic molecules that specifically target the foreign organism.

Conversely, the developmental fate of an endoparasitoid depends on its ability to suppress the host’s immune system.

Drosophila in the wild suffers massive mortality from the attacks of parasitoid wasps. As many as 80% of Drosophila larvae in natural environments may be killed by wasps that lay eggs in them. As many as 350,000 species of parasitoid wasps may inhabit the natural world, an indication of their enormous importance in ecology and evolution. The species they parasitize have evolved diverse defenses to protect themselves against these parasitoids. Some defenses operate at the cellular and behavioral level.

In immuno-competent larvae of Drosophila melanogaster, the cellular immune response against the eggs of endoparasitic wasps involves the proliferation and differentiation of larval blood cells and their participation in cellular encapsulation of the eggs of the parasitoid and in the generation of cytotoxic molecules. In Drosophila larvae, the most numerous blood cell type in circulation is the plasmatocyte. However, when an immune response is elicited against a foreign entity (e.g., parasitoid), plasmatocytes rapidly multiply and subsequently transform into large flattened cells called lamellocytes. Foreign organisms that are too large to be phagocytosed are surrounded by numerous lamellocytes and concealed within a multilayered capsule. Another type of blood cell that participates in immune responses is the crystal cell, which is characterized by dark, rectangular, paracrystalline inclusions that contain enzymes. The main role of crystal cells during an immune reaction is to come in contact with the foreign surface, lyse, and release enzymes that cause the formation of melanin and the synthesis of cytotoxic molecules during cellular encapsulation.

For this response to be effective, timing may be essential. The encapsulation should be completed in less than 48 hr (before parasitoid egg hatches), as the moving larva is likely to escape from the forming capsule.

As much as Drosophila is evolving its combat against Wasps, the wasps have also evolved various mechanisms to evade Drosophila’s immune system.

It is generally acknowledged that passive protection against cellular encapsulation is afforded to those endoparasites that either develop in host locations inaccessible to immune cells or possess molecular surfaces that the host fails to distinguish as nonself.

wasps introduce immune-suppressive substances (e.g., virus-like particles, polydnaviruses, proteins, or venom of maternal origin) into the host at the time of oviposition. Virus-like particles, presumably target-specific immunity cells, adversely affecting their ability to recognize nonself, to form melanotic capsules, and/or to synthesize cytotoxic molecules.

The venom affects the hemocytes, the lymph gland, or melanization. The venom contains soluble proteins and peculiar vesicles with unclear biogenesis, which are likely involved in parasitic success. These purified vesicles target the host lamellocytes, changing their shape from discoidal to bipolar, which prevents them to adhere and form a capsule, or inducing their lysis. Venomics analysis allowed identifying the main venom proteins like P40  and LbGAP associated with the vesicles.

Endoparasitoids that succumb to host encapsulation presumably lack or have diminished immune-suppressive capabilities.

Apart from these cellular combats between the two species, there comes another strategy evolved by Drosophila that is a behavioral response which is through the visual perception that is activated at the sight of wasps.

The sight of wasps induces the dramatic upregulation in the fly nervous system of a gene that encodes a 41-amino acid micro peptide. Mutational analysis reveals that the gene is essential for mating acceleration.

Exposed flies start mating more quickly and more in female flies, perhaps due to greater parental investment than males in their offspring. The mating acceleration is elicited by exposure to several wasp species that parasitize Drosophila, but not by other species, inviting a future investigation into the precise nature of the visual cues that drive this response.

Drosophila-parasitoid interaction paves the way to new concepts in insect immunity as well as parasitoid wasp strategies to overcome it and to decipher mechanisms ensuring parasitic success.

These distinctive associations between various Drosophila species and solitary endoparasitic wasps make for great experiments for studying the population dynamics of coevolving host resistance and parasitoid virulence.

By-Amulya

Nandini

Chhavi

Deepanshi

(B.Sc. Life Sciences, Miranda House, University of Delhi)

References:-

• Emily Vass, Anthony J. Nappi, Fruit Fly Immunity: The fruit fly provides a suitable experimental model for studying various aspects of the cellular and humoral mechanisms, genetics, signaling cascades, and cytotoxic molecules involved in insect innate immunity, BioScience, Volume 51, Issue 7, July 2001, Pages 529–535, https://doi.org/10.1641/0006-3568(2001)051[0529:FFI]2.0.CO;2
• Ebrahim, S.A.M., Talross, G.J.S. & Carlson, J.R. Sight of parasitoid wasps accelerates sexual behavior and upregulates a micro peptide gene in Drosophila. Nat Commun 12, 2453 (2021). https://doi.org/10.1038/s41467-021-22712-0
• Kim-Jo C, Gatti JL, Poirié M. Drosophila Cellular Immunity Against Parasitoid Wasps: A Complex and Time-Dependent Process. Front Physiol. 2019;10:603. Published 2019 May 15. doi:10.3389/fphys.2019.00603
• Kim-Jo, C., Gatti, J. L., & Poirié, M. (2019). Drosophila Cellular Immunity Against Parasitoid Wasps: A Complex and Time-Dependent Process. Frontiers in physiology, 10, 603. https://doi.org/10.3389/fphys.2019.00603
• Carton, Yves & Bouletreau, M. & Alphen, Jacques & van Lenteren, Joop. (1986). The Drosophila parasitic wasps.

LANGUAGE OF BACTERIA

Chirping of birds, barking of dogs, dancing of bees, cry of a child or a roar of a lion: – is there something common amongst them? Yes! All of them are trying to communicate; their anger, fear, anxiety, and happiness to other members of their group. Every organism has their own language, be it sound or their actions. But can unicellular organisms also communicate? Answer to this question is yes, unicellular organisms not only communicate but they also help each other by bartering the cytoplasmic constituents and chemical signals under normal and in stress conditions. Communication amongst the bacteria of the same species, even interspecies and with the host (in case of pathogenic bacteria) is mediated by two ways: – Contact dependent signaling mechanism and contact independent quorum sensing.

Contact dependent quorum sensing

Contact dependent signaling mechanism occurs when one cell comes in contact with another cell and communicates directly through a thin tube – like structures (Ex. pili, curli, fibril etc.) and spherical ball-like membrane vesicles which release from the surface of bacteria and fuse with the membrane of other bacteria.

Contact independent quorum sensing. Competitive interaction between two bacterial species. (Quorum Gun represents quorum molecule, ABX1 and ABX2 indicates two different antibiotics released due to quorum molecules of two bacterial species.

Bacteria not only communicate amongst themselves but also communicate with their environment by using flagella, curli, fibril and fimbriae. Flagella helps the bacteria to sense the surface and other structures like curli, fimbriae, fibril helps them to interact with the host cells, sometimes this interaction is beneficial to the host as in case of pinecone and squid fish where the bacteria (Vibrio fischeri) emits bioluminescence which helps fishes to escape their predators as their prey’s shadow no longer exists. In case of leguminous plants, Rhizobium – a genus of Gram-negative soil bacteria fixes nitrogen and prevents other bacterial species even pathogenic ones from forming  colonies in plant but this interaction is not always beneficial to the host.  It is disadvantageous in the case of injury of skin and soft tissue (blood, lungs) caused by the released toxins and degradative enzymes of Staphylococcus aureus. Another group of gram negetive bacteria such as B. Cereus, causes both intestinal and nonintestinal infections in humans. It is most commonly associated with food poisoning and acute diarrheal disease caused due to release of toxins and hemolysins.

Studying bacterial communication not only helps us to understand the interaction amongst bacteria and its host but also helps us to develop novel ideas like search for molecules from marine bacteria and other organisms to treat the infectious diseases. One such drug which inhibits the communication in Staphylococcus is savarin and more such drugs are yet to come and make our interest flourish in basic science so that more of such novel therapies can be developed to treat infectious diseases.

Written By –

Navodita Seth and Aastha

Biomedical Science (3^rd Year)

Acharya Narendra Dev College University of Delhi

REFERENCES:-

1. Abisado RG, Benomar S, Klaus JR, Dandekar AA, Chandler JR. Bacterial Quorum Sensing and Microbial Community Interactions. mBio. 2018 May 22;9(3):e02331-17. doi: 10.1128/mBio.02331-17. Erratum in: MBio. 2018 Oct 2;9(5): PMID: 29789364; PMCID: PMC5964356.
2. Singhi D, Srivastava P. Role of Bacterial Cytoskeleton and Other Apparatuses in Cell Communication. Front Mol Biosci. 2020 Jul 16;7:158. doi: 10.3389/fmolb.2020.00158. PMID: 32766280; PMCID: PMC7378377.
3. Zhao J, Li X, Hou X, Quan C, Chen M. Widespread Existence of Quorum Sensing Inhibitors in Marine Bacteria: Potential Drugs to Combat Pathogens with Novel Strategies. Mar Drugs. 2019 May 8;17(5):275. doi: 10.3390/md17050275. PMID: 31072008; PMCID: PMC6562741.
4. Le KY, Otto M. Quorum-sensing regulation in staphylococci-an overview. Front Microbiol. 2015 Oct 27;6:1174. doi: 10.3389/fmicb.2015.01174. PMID: 26579084; PMCID: PMC4621875.
5. Rutherford, S. T., & Bassler, B. L. (2012). Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harbor perspectives in medicine, 2(11), a012427. doi: 10.1101/cshperspect.a012427
6. Checcucci A, DiCenzo GC, Bazzicalupo M and Mengoni A (2017) Trade, Diplomacy, and Warfare: The Quest for Elite Rhizobia Inoculant Strains. Front. Microbiol. 8:2207. doi: 10.3389/fmicb.2017.02207

CINDERELLA OF GENETICS – The Mankind’s panacea!

Decades ago, in the year 1979, Jeffrey described the first DNA sequence polymorphisms [A.J. Jeffreys] Since then, there has been a quantum leap in the field of genetic research with Drosophila melanogaster being the researcher’s best-loved.Losing any one of the senses poses a challenge to the well-being of an individual. PRESBYCUSIS, also known as Age-related
hearing loss (ARHL) is found to be mostly burdening the aging population and to your amazement also affects the tiny fruit fly Drosophila melanogaster.
 

Hearing loss is the common sensory disorder that reflects dysfunction of the auditory signal transduction affecting personal communication. Globally 1.23 billion people aged over 65 experience hearing impairment and 50% out of all the cases have genetic components involved.Though, studies involving mouse models have also identified numerous candidate
genes for human deafness bringing it to a total of 154. Yet, a broader perspective explaining the underlying homeostatic machinery of ARHL is still missing. Consequently, to resolve such issues, the researchers at UCL Ear Institute assessed the hearing ability of Drosophila melanogaster across its life span of around 70 days. The feasibility in testing the role of individual genes and fundamental biophysical similarities between vertebrate and Drosophila’s ear makes it an ideal tool for studying hearing loss in humans.
 

Hearing in Drosophila melanogaster is facilitated through (fig) the Johnston’s organ (JO), analogous to the human cochlea (the inner auditory fluid-filled portion of the ear), and is present in the pedicel of its antenna serving as a detector for courtship songs [Albert&Gopfert] Following the experimentation, it was found that: [Keder et.al,]:

1. All parameters of sensitive hearing start declining after 50 days of age (at 25 degrees Celsius) and a complete breakdown of the homeostatic mechanism regulating hearing at day 70.
2. Younger flies (10-50 days old) increased their locomotor activity in response to a 15 minutes long courtship song whereas old flies (60 days) didn’t.
3. The lack of feedback is not a loss of mating interest per se rather it is attributed to the auditory defect.
4. As the days passed, the expression of 36.66% of all 16,243 genes expressed in the 2nd antennal segment changed.

The scientists identified a new set of transcriptional regulating genes conserved between flies and humans, [ for example – Onecut (closest human orthologues: ONECUT2, ONECUT3)] involved in the homeostatic mechanism of hearing before it goes astray with aging. Researchers advocate that by increasing (overexpressing) or silencing (RNA interference), some of the homeostatic genes could be manipulated thereby preventing the flies from getting ARHL which could assist in finding a preventive treatment for ARHL in humans.
 

Today’s cutting-edge era demands a meteoric change in all walks of life and medical health care is expected to deal with a bunch of complex diseases resulting from a combination of multiple genetic and environmental factors. For exploring the cure to major incurable diseases such as Fibrodysplasia ossificans Progressiva, Cancer, glioma, Multiple endocrine neoplasia type 2, etc. fly’s genome has proved to be the paragon of disease models time and again.   This scientific breakthrough in reversing the hearing impairment of humans will be an augmenting discovery
making space for the arrival of Drosophila melanogaster as an emerging tool in the field of personalized medicine for the next generation Genomics 2.0 [Kasai&Cagan]

Featured image is the copyright of the author

References

1. A.J. Jeffreys. DNA sequence variants in the G gamma, A gamma, delta- and beta-globin genes of man. CELL, 18 (1979), pp. 1-10.
2. Review- Cochlear homeostasis and its role in genetic deafness. Journal of otology. (2009). Vol. 4; Issue No. 1, 15-22
3. Keder et.al, Homeostatic maintenance and age-related functional decline in the Drosophila ear. Scientific Reports, (2020);10(1)
4. Kasai & Cagan. Drosophila as a tool for personalized medicine: a primer; Personalized Medicine (2010)7(6),621-632.
5. Albert & Gopfert. Hearing in Drosophila, Current Opinion in Neurobiology (2015),34:79-85

By:-

Arukshita Tyagi

Pursuing Bachelors in Zoology

Miranda House, University of Delhi

Neuroscience and Fruit flies

As Francis Crick once quoted “There is no scientific study more vital to man than the study of his own brain. Our entire view of the universe depends on it.” And there is no denying to it because studying neuroscience advances our understanding of basic biology and our body
function. Knowing how things typically work can help shed light on many aspects of the human body including thoughts, emotions, behaviour, and what may happen when there are problems. It can help researchers find ways to prevent or treat problems that affect the brain, nervous
system, and body.

Discoveries in tiny fruit flies (Drosophila melanogaster) have contributed greatly to unravel the mysteries of neuroscience by working as an attractive and effective model organism for a number of scientific studies for years and thus enabling milestone discoveries in this field and triggering many research projects. Thomas Hunt Morgan and his colleagues were the first one who made remarkable discoveries with fruit flies a century ago and then started this endless scientific expedition of using Drosophila melanogaster as a model system. And no doubt it is an invaluable and highly fruitful model system. It has enabled dramatic advances in almost every field of biology including cell and developmental biology, neurobiology and behaviour, molecular biology, evolutionary and population genetics including several other fields.

Even after more than 100 years fruit flies continue to be the premier research organism for many neuroscientists due to its various unique advantages and along with the combinational use of the latest powerful research tools, in recent times, many major breakthroughs have occurred in the field of vertebrate neuroscience. Some of the important studies are listed below.
● Fly has provided us with information about the fundamental features of the nervous system, development of the nervous system, its organisation and function, how information can be integrated and processed, how specific genes can cause neurodegeneration and what gene products and genetic cascades control behaviour.
● It has helped to unravel the principles of development, pattern formation and vertebrate nervous system segmentation.
● Studies on the proneural helix-loop-helix proteins which are basically expressed in neuronal precursors of the Central nervous system (CNS) and Peripheral nervous system (PNS). They are also often required to allow ectodermal cells to adopt a neural fate. And several other proteins that affect the functioning of the nervous system.
● Flies are used to understand neurogenesis, neuronal migration, growth cone guidance, synaptic transmission, circadian rhythms, behavioural neurogenetics and so on.
● Understanding the molecular and cellular basis of behaviour (Chemotaxis, aggression, physical response, escape behaviour, sex) by utilising a wide array of genetic tools.
● Studies on sleep in flies are paving the way for a better understanding of sleep in vertebrates as flies just like vertebrates require sleep and various aspects of physiological properties of sleep are shared between Drosophila and humans.
● Recent studies show ‘neural encoding’ in fruit flies that how they respond behaviourally to sound, gravity and wind. For instance, agitated flies move against gravity, exposure to male courtships results in reduced locomotion in females. Johnston’s hearing organ is the antennal ear of fruit flies (also present in mosquitoes and honey bees) which serves
as a complex sensor for all mechanosensory stimuli (like wind and gravity). These auditory and non-auditory signals travel in parallel from fly ear to brain feeding into neural pathways. These pathways are strikingly similar to that which occur in the human brain, thus studied extensively for auditory research and to understand acoustic communication, neural circuits, processing and integration of sensory information in the brain and neural encoding mechanism which involve the transformation of neural
sensory information to behaviour.
● To study neurogenetics of courtship and mating in fruit flies. To attract females during courtship male sing songs (Let music sound while she doth make her choice). The song features indicate male fitness and associated mechanism for how it is perceived from auditory signals by the females (Acoustic communication).
● Not only adults but also Drosophila larva are used to study fundamental questions of neuroscience, it offers a seemingly unlimited genetic toolbox which allows one to visualize, silence or activate neurons down to the single-cell level combined with its simplicity with cell no. offers a useful system to study associative odour-taste learning and memory formation.
● The recent contribution of research in flies relates to Parkinson’s disease (a CNS disorder) and many other neurodegenerative diseases like ataxias.

As outlined above fruit flies always have and will continue to contribute to many aspects of neuroscience. And with already proven potential, current and future research will pave the way to new genes, new pathways and new approaches that will pioneer numerous fields of neurobiology. As they say, If you can grasp the reason, master the process, appreciate the truth of the necessity of work, it turns out to be easy as enough synapses have already been created in your mind (and Drosophila‘s mind too).

References:

Matsuo E, Kamikouchi A. Neuronal encoding of sound, gravity, and wind in the fruit fly. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2013;199(4):253-262. doi:10.1007/s00359- 013-0806-x
Kamikouchi A. Auditory neuroscience in fruit flies. Neurosci Res. 2013;76(3):113-118. doi:10.1016/j.neures.2013.04.003
Ishikawa Y, Kamikouchi A. Auditory system of fruit flies. Hear Res. 2016;338:1-8. doi:10.1016/j.heares.2015.10.017
Murthy M. Unraveling the auditory system of Drosophila. Curr Opin Neurobiol. 2010;20(3):281-287 doi:10.1016/j.conb.2010.02.016

Clemens J, Girardin CC, Coen P, Guan XJ, Dickson BJ, Murthy M. Connecting Neural Codes with Behavior in the Auditory System of Drosophila [published correction appears in Neuron.
2018 Jan 17;97(2):475]. Neuron. 2015;87(6):1332-1343. doi:10.1016/j.neuron.2015.08.014
Pang R, Fairhall AL. Let Music Sound while She Doth Make Her Choice. Neuron. 2015;87(6):1126-1128. doi:10.1016/j.neuron.2015.09.014
Nadrowski B, Effertz T, Senthilan PR, Göpfert MC. Antennal hearing in insects–new findings, new questions. Hear Res. 2011;273(1-2):7-13. doi:10.1016/j.heares.2010.03.092
Widmann A, Eichler K, Selcho M, Thum AS, Pauls D. Odor-taste learning in Drosophila larvae. J Insect Physiol. 2018;106(Pt 1):47-54. doi:10.1016/j.jinsphys.2017.08.004
Gerber B, Stocker RF, Tanimura T, Thum AS. Smelling, tasting, learning: Drosophila as a study case. Results Probl Cell Differ. 2009;47:139-185. doi:10.1007/400_2008_9
Bellen, H. J., Tong, C., & Tsuda, H. (2010). 100 years of Drosophila research and its impact on vertebrate neuroscience: a history lesson for the future. Nature reviews. Neuroscience, 11(7), 514–522. https://doi.org/10.1038/nrn2839

Featured Image Illustration is Copyright of Author

By:-

Disha Chaudhary

Pursuing Bachelors in Life Sciences

Miranda House, University of Delhi

Comprehending the Science of Symmetry

Have you ever wondered why isn’t your nose at the place of your ears and vice-versa? Why isn’t our head at the posterior end while legs at the anterior? What if we come across someone with features very different from us? The science behind the symmetry in an animal’s body lies in its genome and is uniquely presented in different animal groups.

It all begins from a single cell zygote, which after repetitive divisions, growth and differentiation gives rise to a fully transformed individual with legs, hand, eyes, nose, ears all at their appropriate positions. How fascinating it is to know that all the information required to develop into an adult organism is all contained in that tiny single and first cell of life and to decipher the understanding of the same was a major scientific challenge before. Later a group of genes known as homeobox (HOX) genes were discovered as an important master regulators of development, to appreciate the underlying phenomenon. Highly conserved throughout evolution, these are expressed spatially and temporally in a very well coordinated manner right from the embryonic development to in virtually all tissues and organs throughout adult life. Discovered originally in Drosophila, these genes act as markers of position along the anteroposterior axis of the body. They are the developmental genes that code for proteins that function as regulatory transcription factors during embryogenesis. Present in the genomes of all animals which have been mapped so far in addition to the genomes of plants and fungi, these genes indicates the ancient origin and the divergence of these kingdoms (homology) though initially it was thought to govern the segmental identity along the antero-posterior (AP) axis only in Drosophila but later got cloned and analyzed in a vast array of animal groups from hydra to humans and identified as conserved in vertebrates and are expressed during early gastrulation stage (where the embryo generates its major body axis) in developing vertebrates.

Fortuitously discovered while following the observation of two striking mutations in Drosophila melanogaster where in one mutation, the antenna got transformed to the legs while in other the haltere(balancing organ in fruit fly) into the wings, its discovery has been proved to be one of the best
tools to unravel the mystery of positioning of body organs. In Greek, homeosis signifies a change of a complete body structure into another thus the changes were termed as ‘homeotic transformations’ while the genes were recognized as ‘homeotic selector gene’ or ‘HOX gene ’, by Drosophila geneticists conceptualizing that it could control the development of every segment of the fly. Since their discovery, Hox genes provide a paradigm for several areas in modern biology including developmental biology and molecular genomics. In addition to their role in AP patterning, these genes
have yielded stupendous potential for various useful applications including numerous cancer research, limbs associated normalities, and much more. It has also played a pivotal role in the evolution of novel body plans within Bilateria.

A total of 39 HOX genes have been isolated in the human genome (vertebrate), which are located on 4 different chromosomes, and are structurally and functionally homologues to the HOX genes of Drosophila (invertebrate, possess a single Hox cluster). Of these, mutations in 10 Hox genes have been found to cause human disorders with remarkable variation in their inheritance patterns, penetrance, expressivity, and mechanism of pathogenesis.

Recent numerous studies have also revealed the importance of Hox genes in the development of many organ systems. Specific HOX genes are employed for specific organ development such as the Hox3 genes for thymus, thyroid, and parathyroid development, Hox5 genes in lung development, Hox6 genes in pancreas development, Hox9,10,11 genes in the reproductive tract, etc. Both upregulation (the process of increasing the response to a stimulus) and downregulation (the process of reducing or suppressing a response to a stimulus) of the Hox genes, particularly the transcription factors are often linked to promote carcinogenesis indicating the importance of transcriptional mechanisms of HOX genes in promoting normal adult tissue homeostasis. Altered expressions of several HOX genes are responsible for various types of cancers of breast, lung, colon, ovary, kidney, etc. For instance, HOXA (a Hox gene) altered expression is reported to have a role in breast and ovarian cancer. Several abnormalities in human limb formation have been recently linked to specific Hox genes. Synpolydactyly (SPD)is a rare, inherited limb malformation with a joint presentation of both syndactyly (fusion of digits) and polydactyly (extra digits), is caused by mutations in HOXD13. To maintain tissue homeostasis, to understand the evolutionary significance, to direct the undifferentiated mass of cells in the embryo and while living in an era where getting diseased is as easy as breathing air, there is a much need to understand the potential roles of these genes and employ it to fathom the unresolved and upcoming abnormalities.

REFERENCES:
 HOX GENES: Seductive Science, Mysterious Mechanisms, Terrence RJ Lappin, David G Grier,
Alexander Thompson, Henry L Halliday , Ulster Med J. 2006 Jan; 75(1): 23–31.
 Regeneration, repair and remembering identity: the three Rs of Hox gene expression, Kevin C.
Wang, Jill A. Helms, Howard Y. Chang
 The regulation of Hox gene expression during animal development, Moisés Mallo, Claudio R.
Alonso, Development 2013 140: 3951-3963
 Hunt, P. (1998). Chapter 13 The function of hox genes. Principles of Medical Biology, 261–291. 
 Hox genes: a continuation of embryonic patterning? Richard Morgan

Featured image is copyright of the author

By:-

Gunjan Goyal

Pursuing Bachelors in Life Sciences

Miranda House, University of Delhi

Invertebrate Astronauts

Stephen Hawking once stated, “I don’t think the human race will survive the next thousand years unless we spread into space; we need to reach out to the stars”. Life, however, faces severe challenges in the barbarous environment of spaceflight. Astrobiology research aims to devise future human exploration missions far away from Earth by first developing an understanding of the effects of spaceflight on living systems, coupled with extensive ground-based research. On Earth, it is common practice to employ animal models to understand human health concerns. A similar study of organisms in the Earth’s orbit helps learn how Earth-based life forms can adapt and flourish in harsh space environments. Most of us know about monkeys or mice as pioneers of biological research in extra-terrestrial regimes but little do we know about the role played by lower invertebrates(animals lacking a notochord or vertebral column) in this arena. Experimentation with invertebrate models offers an economical, yet thorough understanding of complex physiological processes, while avoiding ethical complications posed by mammalian models.

The most popular invertebrates for astrobiological research are Tardigrades. Tardigrades, also referred to as water bears, are eight-legged, microscopic organisms found on moss or other wet environments. They are suitable for Space Research as they can resist complete desiccation and DNA damage induced by space vacuum, extreme temperatures and solar radiation. The general effect of vacuum on living cells is extreme dehydration, which in turn may lead to irreversible changes in structural and biochemical components of the cell. Tardigrades, very cleverly, combat this by turning into a specialized ball-like structure called “tun” and entering into an “anhydrobiotic state”(literally meaning- life without water) during which they release all water from their body and suspend all major metabolic activities; they do not show any signs of life at the metabolic level but may resume life after rehydration- this process is called cryptobiosis. (Alpert, 2005; Clegg, 2001). They are probably the toughest
animals on earth and are claimed to have survived 5 mass extinctions. Yes,
they are older than dinosaurs!

Other popular invertebrate models for space biology are the nematode
(C.elegans) and fruit fly (Drosophila melanogaster). Experimentation with
these models is relatively easy and quite economical. Both these organisms
produce a large number of progenies in a short period which enables us to
rapidly observe the processes of reproduction and development in space
environments. Since these organisms adapt to extreme conditions of space by altering the expression of certain metabolic genes, their completely mapped genome offers advance bioinformatics tools for extensive analysis of the genetic modifications. Drosophila, in particular, shares around 70%
homology with the human genome; thus behavioral or molecular analysis of the insect in space reflects parallel responses in humans. Lack of surplus air, food, water along with significant health risks posed by high radiation levels and low gravity in outer space are some challenges that need to be overcome if we are to explore the moon, Mars and beyond. Understanding how model organisms thrive in space by repairing cellular damage and protecting themselves from infection in conditions of microgravity will eventually help us seek the knowledge required for supporting long term human habitation in outer space.

REFERENCES:
1) Jonsson,K.I. Tardigrades as a potential model organism in Space
Research. Astrobiology,7(5),757-766.
2) Wełnicz, W., Grohme, M. A., Kaczmarek, Ł., Schill, R. O., & Frohme, M.
(2011). Anhydrobiosis in tardigrades—The last decade. Journal of Insect
Physiology, 57(5), 577–583.
3) Szewczyk, N. J., Mancinelli, R. L., McLamb, W., Reed, D., Blumberg, B. S., &
Conley, C. A. (2005). Caenorhabditis elegans Survives Atmospheric
Breakup of STS-107, Space Shuttle Columbia. Astrobiology, 5(6), 690–705.
4) https://www.nasa.gov/ames/research/space-biosciences/space-
biosciences-research-branch
5) https://www.nasa.gov/pdf/185052main_FSB2000-2002REPORT.pdf

Featured image is copyright of the author

By:-

Ayushi Das

Pursuing Bachelors in Zoology

Miranda House, University of Delhi

Cancer research fueled by the fruit fly: A hundred year bond started by a woman

The wide and important role of the humble fruit fly began with its contribution in genetics by Morgan’s experiment in 1910 but Drosophila’s appearance in the cancer research field wasn’t until 1918 when Mary Bertha Stark elucidated the presence of tumors in Drosophila melanogaster. Through the shadows of leading men, a woman questioned the role
of chromosomes in cancer using these flies and started working on it broadly. At this point, no one, not even M. Stark had imagined the impact of her work and the huge role this little fly would play over the next hundred years. Through this journey, Drosophila has been used as a
model to describe various oncogenic pathways and basic processes that regulate human cancers, such as the competitiveness of cancer stem cells (CSCs), the importance of tumor microenvironment, cancer cachexia (a wasting syndrome characterized by weight loss, anorexia, asthenia, and anemia) and now, even in drug resistance. Now it’s common to wonder how and why this fly becomes so important and the answer lies in its genome, as it does for the most fascinating questions of the world.

Basically, why Drosophila? According to a lot of scientists, humans are brothers to mice and first cousins to flies as we share 99% and 60% of our genes, respectively. It’s because of this 60% homology in the genome and numerous other advantages like brief generation time, low maintenance costs, and availability of powerful genetic tools in Drosophila that the cancer research projects which use it as a model organism have increased exponentially, especially in the last 10 years.

Cancer is characterized by an unrestrained growth of cells. At the cellular level, this extensive uncontrolled growth is due to the activation of proto-oncogenes (e.g., the RAS/RAF/MAPK axis) and loss of functioning of the tumor suppressor genes (e.g.- T53 gene, etc.) due to mutations. These cancer cells become so smart that they learn to live with extensive changes in their environment, can thrive even in low-oxygen surrounding (Hypoxia), and can escape their death (apoptosis) by signaling anti-apoptosis pathways. But the great news is that most of the signaling pathways controlling cell growth and invasion in mammals have a conserved function in flies which allows alteration in their easy-to-study-small-genomes to mimic the tumor’s biology in a simple model organism. This process of cancer modeling took a giant leap when unbiased genome-wide genetic screens and powerful recombinant techniques were developed. It is because of these genetic screens, “The hippo tumor suppressor pathway” was discovered and we continue to identify genes responsible for tumor growth in various parts of the body. Thus, we keep increasing and refreshing our understanding of transformation and metastasis in human systems through the novel fruit fly, and most times, we credit this development to men who have worked in genetics. But this our ode to the underrated genius of Mary Bertha Stark who paved a whole new way for hundreds of scientists by using the little fruit fly, Drosophila melanogaster, whilst also inspiring young female minds(including mine) to believe in themselves and pursue that belief till it gets them where they want to be.

Featured Image is by the author

By:-

Lavina Mulani

Pursuing Bachelors in Life Sciences

Miranda House, University of Delhi

NATURE’S FIGHT CLUB – SINK OR SWIM

Evolution is an all-pervading phenomenon in nature and occurs constantly around us, although at an extremely gradual pace.

One such evolutionary spectacle that is occurring constantly is host-parasite co-evolution – the simultaneous evolution of the host and the parasite with respect to each other.  Hosts are continuously evolving different mechanisms of protection against the parasite. On the other hand, the parasite is also evolving to counter and dodge these host mechanisms to continue its life cycle and protect itself.

So what we are looking at is basically like an arms race between the host and the parasite. What happens when nature introduces a third party in the midst of this process? This third party comes in the form of defensive endosymbionts – microorganisms living inside the host that confer resistance against the parasite. They are able to do this either by the production of toxins or by triggering the hosts’ immune response against the parasite. It can also compete with the parasite for resources, as they both have to exist within the same host body.

To understand this, lets take the example of Drosophila neotestacea, a fruit fly species found in North America. A parasitic nematode worm, Howardula aoronymphium that causes sterility, infects this fly species. It was observed that the presence of a bacterium called Spiroplasma inside some members of the fly population, rescued them and restored their fertility to a great extent. The manner in which this bacterium counters the nematode is by the production of a protein (a ribosome inactivating protein) that is toxic for the worm. Spiroplasma itself is not recognized as a pathogen by the fly and the immune response is not directed towards it, probably because the bacterium lacks a cell wall. Due to the success of this mechanism of defense, selection has acted on the fly population and has caused a rapid spread of Spiroplasma in D. neotestacea populations across North America. Similarly, in the case of beewolves (bee- killer wasps), the symbiont, Streptomyces, produces a mixture of antibiotics that repress fungi pathogens. Thus, the introduction of a third party can affect the dynamics of host-parasite co-evolution.

So where do we go from here? We now know that defensive symbiosis is a valuable weapon to have in one’s arsenal in this arms race against parasites and disease. But how do we use this weapon? Just like nature has introduced a third party into the middle, what if we did the same thing? Rather than producing drugs as a mode of protection against viruses like dengue, chikungunya and Zika and other parasites, for which they can simply evolve counter adaptations, it makes more sense, at least in theory, to counter these parasites with endosymbionts that can coevolve and change with them.

Wolbachia is an endosymbiotic bacteria found in Drosophila melanogaster and several other arthropods. In Wolbachia-infected insects that also act as vectors for disease causing viruses, the bacterium does not allow the transfer of these viruses to new hosts and thus, has the potential to prevent the spread of that particular disease. If the insect that is acting as a vehicle for the virus is no longer suitable for it due to the presence of Wolbachia then either the virus must evolve and adapt to new ways of transmission or run the risk of dying out.

One such insect is the mosquito, Aedes aegypti that transmits the dengue virus. Scientists have transferred the bacterial strains of Wolbachia found in D. melanogaster into these mosquitoes in the lab. Then, they released these mosquitos to mate with their uninfected counterparts in natural, wild populations, in an attempt to curb the spread of this disease. This is a promising new approach of attempting to stop the spread of insect mediated viral diseases but for how long it will be effective, depending on how the coevolutionary mechanisms work, remains to be seen.

Evolutionary studies like these, can improve our understanding of complex evolutionary mechanisms and Drosophila, along with several other organisms has contributed greatly towards this end.

REFERENCES:

1) Vorburger, C., & Perlman, S. J. (2018). The role of defensive symbionts in host-parasite coevolution. Biological Reviews. 1747-1764.

2) Jaenike, J., Unckless, R., Cockburn, S. N., Boelio, L. M., & Perlman, S. J. (2010). Adaptation via Symbiosis: Recent Spread of a Drosophila Defensive Symbiont. Science, 329(5988), 212–215.

3) Hamilton, P. T., Peng, F., Boulanger, M. J., & Perlman, S. J. (2015). A ribosome-inactivating protein in a Drosophila defensive symbiont. Proceedings of the National Academy of Sciences, 113(2), 350–355.

4) Schmidt, T. L., Barton, N. H., Rašić, G., Turley, A. P., Montgomery, B. L., Iturbe-Ormaetxe, I., Turelli, M. (2017). Local introduction and heterogeneous spatial spread of dengue-suppressing Wolbachia through an urban population of Aedes aegypti. PLOS Biology, 15(5), e2001894.

5) Ballinger, M. J., & Perlman, S. J. (2018). The defensive Spiroplasma. Current Opinion in Insect Science.

Featured Image Illustration is by the Author

By:-

Nitika Chandra

Pursuing Bachelors in Life Sciences

Miranda House University of Delhi

TO TRUST YOUR GUT OR NOT?

Comedian Stephen Colbert once christened the gut, “pope of your torso” considering the enteric nervous system’s autonomy and infallibility. The only organ to boast its own independent nervous system with an intricate network of 100 million neurons embedded in the gut wall, is also often referred to as the second brain. Recall the last time you made a decision wholly based on your GUT FEELING or a moment, when you just knew in a jiffy that this is right or not. Has it ever crossed your mind, why is it
called the gut feeling and not nose, ear or blood feeling…?? It is simply because there exists a cross talk between the gut and brain.

The human intestinal tract is essentially sterile right at birth. The gut microbiota evolves during early life until a unique, subject-specific (fingerprint) adult-like community arises, which is relatively stable throughout life. A unique combination of different populations of organisms inhabits our gut, mainly bacteria but also archaea, viruses and protozoa, roughly approximating 10¹⁴ , outnumbering the human cells in our bodies by a factor of 10. Almost 99% of the bacteria in the gut are
anaerobes while caecum houses mainly aerobic bacteria. Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria are the four dominant bacterial phyla. Fungal genera that have been found in the gut include Candida, Saccharomyces, Aspergillus, Pleospora, Bullera amongst others. Archaea is the other class of gut flora, important in the process of bacterial
fermentation.
Gut homeostasis is maintained if certain commensals and mutualists are maintained in the gut, which regulates inflammatory responses and tissue regeneration. Dysbiosis in the gut may lead to dysregulated gut-brain axis and may be responsible for irritable bowel syndrome (IBS). Analysis of human fecal sample, mice models and insect models such as Drosophila are further providing insights into this. Short neuropeptide F (sNPF), a relative of mammalian neuropeptide Y (NPY) ind Drosophila is involved in Gut-brain signal. sNPF is activated under metabolic stress such as fasting and maintains the gut integrity. The gut-brain communication is responsible for its release.

Stock Image- Gut-Brain Axis

From the old translations of Hebrew and Greek texts of the Bible such as the King James Bible of 1611, a relationship between the gut and brain has long been recognized. In the quotations, it is not only the bowel that is affected by emotions (‘my bowels are troubled’) but even vice versa (‘my bowels were moved for him’). Gastroenterologist Emeran Mayer, MD, director of the Center for Neurobiology of Stress at the University of California, Los Angeles says that, “When you consider the gut’s multifaceted ability to communicate with the brain, along with its crucial role in defending the body against the perils of the outside world, it’s almost unthinkable that the gut is not playing a critical role in mind states.”
For all of its importance to mental well-being, you might expect that the brain is where we will find the ‘happy hormone’ i.e. serotonin, but it’s
not. To your astonishment, about 95% of it is estimated to be found in gut and the remaining 5% found in brain. Peripheral and central nervous systems can easily be modulated by changes in gut microbiota resulting in altered brain functioning, and suggesting the existence of a microbiota gut–brain axis. The bidirectional gut-brain communication not only ensures the proper maintenance of gastrointestinal function, but is also likely to have multiple effects on motivation and higher cognitive functions, including intuitive decision-making a process embodied in the term “gut feeling”. The term “gut feeling” widely used in everyday language has number of connotations ranging from intuition, instinctive feeling, making decisions without rational underpinnings, to serendipity. In this context, the popular reference to decisions based on gut feelings may have an actual neuro-biological basis in unconscious signals from the gut. This contention is backed by neuro-imaging studies that implicate sub- regions of the anterior insular cortical regions in intuitive decision-making. It has been suggested that large spindle shaped neurons that are primarily located in the fronto-insular region of the brain, and present in humans and other mammals with complex social interactions, may be involved in such unique cognitive processes. Hidden in the walls of the digestive system, this “brain in your gut” is revolutionizing understanding the links between digestion, mood, health and even the way you think. So the next time you are in a dilemma dig deep within the depths of your gut and you might unearth the solution.

References:
1) Cross, A., Golumbek, P., (2003). Neurological manifestation of celiac
disease- proven or just a gut feeling? Neurology, 60, 1566-1588.
2) Kennedy, P., Cryan, J., Dinan, T., Clarke, G., (2014). Irritable bowel syndrome: a microbiome-gut-brain axis disorder? World journal of Gastroenterology, 20(39), 14105-14125.
3) Palma, G., Collins, S., Bercik, P., Verdu, E., (2014). The microbiota-gut-brain axis in gastrointestinal disorders: stressed bugs or stressed brains or both? Journal of Physiology, 14, 2989-2997.
4) Moss, W., Faller, D., Harpp, O., Kanara, I., Pernokas, J., Powers, W., Steliou, K., (2016). Microbiota and neurological disorders: A gut feeling. Bioresearch open access, 5.1, 137-145.
5) Shi, H., Wang, Q., Zheng, M., Hao, S., Lum, J., Chen, X., Huang, X., Yu, Y., Zheng, K., (2020). Supplement of microbiota accessible carbohydrates prevent neuroinflammation and cognitive decline by improving the gut microbiota-brain- axis in diet induced obese mice. Journal of neuroinflammation, 1-21.

By:-

Pragya Tiwary

Pursuing Bachelors in Life Sciences

Miranda House, University of Delhi