International Symposium organized by the Students of the Graduate School of Life Sciences

    The winner of the Eureka! 2014 Writing Contest is Ankit Turakhiya.

    In the cellular wonderland

    I peered into the microscope, trying to adjust the focus with my right hand. Soon, the cells came into view. They were yeast cells of the species Saccharomyces cerevisiae, the same microbe we find in a glass of Hefeweizen or in a loaf of bread. What made the fragile spheres of the cells appear beautiful were the bright green fluorescent spots, a few of them in each cell. Mesmerised, I sat there, staring into the microscope eyepiece, the image becoming more and more vivid, a far--‐off roar sounding in my ears, becoming louder and louder…

    I opened my eyes and looked around. Everything appeared to be in a haze. I rubbed my eyes; this made it easier to focus. I was suspended in a translucent fluid, floating around. There was a large sphere some distance away from me, emitting ribbons. Filaments, irregularly shaped objects, smaller spheres dotted the fluid--‐ the three--‐dimensional “landscape” around me. And there were other fluorescent green globes around me, swimming in the fluid, bathing everything in a bright green glow. They seemed a familiar green, I tried to remember where I had previously seen this shade of the colour, and with a jolt, the realisation dawned upon me, I was in a yeast cell! The green globes gave it all away! Now as I looked around, more and more of the goings--‐on became clearer to me. The large sphere emitting ribbons that I saw must be the nucleus, the headquarters of the cell releasing messenger RNAs, or the nucleic acid code basis for the cell to make proteins. The other objects were the different cell organelles, important for the cell to keep going. The fluid, or “cytoplasm” as we call it in textbooks seemed to be packed with some other three--‐dimensional structures, smaller, with ribbons, barrels, helices and threads--‐ what were these? As I looked on them emerging curiously from a structure consisting of a smaller and a larger sphere (which were the subunits of a ribosome, the cellular interpreter of the messages of the nucleus), I realized that these were proteins! The fluid was full of them, they were everywhere. Proteins are the building blocks of the cell and the human body; they perform a vast array of functions inside a cell. With new ones being added to the cell each passing minute, one would wonder how this little world dealt with the problem of overcrowding. But then, I saw some of the proteins sporting a weird a tail called ubiquitin, swimming towards a barrel made of small balls, which we call the proteasome. This was a hard working member of the Ubiquitin Proteasome System (UPS), a system with an obviously bureaucratic sounding name, performing the vital task of deciding the fate of the proteins depending on the type of ubiquitin tail they possess. The proteasome degraded them into small pieces and freed the tails to be put onto the next target. Fascinated, I watched this beautiful little world, as scores of nascent proteins came into being and at the same time, other old ones float away to the proteasome, and then to oblivion…and then all hell broke loose!

    The cell, the beautiful serene yeast cell, was racked with a heat shock! Temperatures rose, everything started heating up, the fluid seemed uncomfortably warm, and right before my eyes, the cell appeared to transform. Sirens were ringing and the cell switched to its emergency mode. The little world now focussed on protecting its citizens--‐ the proteins, and stopped producing new ones. Thousands of proteins around me scurried to safety and formed groups. These groups are stress granules, so called for their granular appearance and because they can be seen in greater numbers during times of stress. As most of the proteins sat scared, a few brave ones ventured out, seeking to repair the damage done. Within a few minutes, the cell seemed to relax. The stress had passed; the temperature seemed to become more ambient. And then, from nowhere, a trumpet sounded, startling me. A few of the proteins that were swimming about arranged themselves in two rows, as if welcoming a dignitary. “Curiouser and curiouser”, I thought to myself. And then, lo and behold, in came the royal protein molecules– the kings Cdc48, a whole line of them, tall and majestic, wearing a gold crown. They were of Chaperone descent, a privileged class of proteins. The appearance of the kings brought a surge of hope to the cell. The kings went to the groups of proteins, talked to them and assured them of safety. They encouraged the healthy and happy proteins to come back outside to normal life. As more and more of the healthy proteins gingerly stepped out of the stress granules, the number of these stress granules also went down. I wondered how the kings knew what steps to take in an emergency situation. There must be a retinue of close aides, confidantes. Where was it and who were they? I knew they were called cofactors. We know a few of them already. But for such precise clockwork working of the kings in all situations, there had to be more of them, influencing the decisions and actions of the kings– Cdc48, and thus in turn indirectly dictating the fate of the cell. Who are these unknown cofactors? Which of the hundreds of thousands of molecules milling around me is one? Who are these cofactors…? “Lunch?”, the question brought me back to reality, thumped me back onto the chair. I looked around in darkness--‐ no fluid, no proteins--‐ just darkness. The door to the room was opened a crack, and my colleague called me for lunch. “What are the cofactors?”, I mumbled to myself. “Come on, let’s go, it’s getting late”, my colleague insisted. But I couldn’t silence the voice in my head. I had to find out. As I walked out of the lab into the beautiful sunshine, I was more curious and determined than ever.


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