Skeletal muscles, the kinds we use our bodies and limbs for, are fascinating organ systems. Their essential locomotory functions make them central to quality of life. Other functions you may not have heard about make them a key node in systemic metabolism. Their intricate yet stereotypical structure links bodily activity with physiology at a molecular level. Deviations result in debilitating diseases, many of which are genetically linked. How do they attain such intricate form and retain function throughout our lives?

A lot of what we know about mammalian muscle maintenance from studying their stem cells in vitro. This reductionist approach yields valuable information about how satellite cells behave in a dish. In this talk I will bring to light what we are finding about skeletal muscle maintenance and homeostasis inside a living system where all relevant cues from the muscle environment come together. This living system is Drosophila. Fruit-fly flight muscles bear striking similarities in structure and function to human muscles. They allow us to modulate molecular function at a cellular and molecular level. We showed the existence of the satellite like cells in Drosophila for the first time and the cues they get from surrounding muscles. We now ask further if they respond to physical signals like mechanical tension and through what signaling pathway. 

Further, muscles at a fundamental level are contractile syncytia. Many nuclei coexist and function within the same relatively large cell throughout the animal’s life. We ask if the two ends of the same cell have identical cytological processes active. I’ll be discussing our findings that suggest that a host of molecular differences exist along the length of Drosophila flight muscle cells. We find mRNA for close to a hundred proteins including transcription factors, proteases and ion channels enriched in different regions of the muscle fibre. The differences are critical to the formation and maintenance of muscles. How the activities of so many molecules come together just so that flies can beat their wings at 200 hz over a rotting banana is a new and hugely exciting question with implications for how we view human myodystrophic conditions.

We now know that a large number of behaviours and physiological processes occur at specific times of the day and that they are not mere responses to geophysical cycles caused due to the rotation of the earth on its axis. In most metazoans the endogenous mechanisms that make up these timekeeping entities reside in neuronal networks. I will discuss how circadian pacemaker circuits govern body functions and evidence for how disruptions in clockwork function can be detrimental to overall health.

My undergraduate degree is in Chemistry. I studied Biochemistry during my MSc. I performed PhD research in Molecular Biology - Molecular mechanism of initiation of protein synthesis to be precise. During postdoctoral training, I learned embryology of developing chick limb skeleton. Adult limb skeleton is comprised of multiple elements. However limb skeletal development begins with a single cartilaginous template which is branched (along the long axis) and segmented (perpendicular to the long axis) to give rise to the distinct skeletal elements. Further, while the early limb skeleton is made of pure cartilage, in mature skeleton most of the cartilage is replaced by bone. This cartilage that is replaced by bone is referred to as transient cartilage. Only the cartilage adjoining the plane of segmentation remains as cartilage forever and is varyingly referred to as permanent cartilage or articular cartilage or joint cartilage.

Our goal is to understand how genetic mutations and viral infections cause neurological disease. Disease causing genetic mutations are often difficult to pinpoint due to multiple candidates in a single patient. Variants in a particular gene of interest are frequently discovered in one or very few patients, which does not provide sufficient evidence for a definitive diagnosis. Model organisms can facilitate functional analysis of human variants, promoting disease identification and characterization. The fruit fly is particularly suited for this role with quick and highly sophisticated genetic manipulations. Functional testing of human variants using Drosophila can lead to disease diagnoses, identification of molecular pathogenic mechanisms, and testing of therapeutic targets. We focus on microcephaly, a devastating neurodevelopmental condition that affects brain development and is characterized by reduced brain size. We established a discovery platform to identify novel genetic variants that cause microcephaly using information from patient cohorts. Our goal is to use this platform to investigate mechanisms of disease, but also determine how these pathways function in normal development. In addition to genetic mutations, viral infections can also cause similar neurodevelopmental defects. One such example is Zika virus, which is associated with very severe microcephaly. We developed Drosophila as a model to identify phenotypes caused by viral protein expression. We use the expansive set of genetic tools to determine what conserved pathways viral proteins interact with to cause disease.