On National Science Day, 2022, we started posting a thread of science themed images from the institute. A team of students also participated in a science writing exercise and came up with descriptions of the science behind each of these images.
Link to twitter thread: https://twitter.com/TIFRH_buzz/status/1498304357468708871
(8/n): ‘Will you marry me?’
Sometimes cancer cells spontaneously originate in a tissue due to a deleterious mutation. When cancer cells newly emerge in a group of healthy cells, they are extruded out by a process called cell competition. Praver Gupta (graduate student in Tamal Das’s lab) has captured the image of a 3D cyst, wherein healthy
cells (in yellow) work in concert to push out a cancerous cell (in violet) and hence, reduce the risk of cancer. Ironically, what might appear here as a ring intended towards a union is, in reality, quite the opposite!
Scale bar: 10 microns
Image: Praver Gupta
Description: Piyush Daga (with inputs from Shravasti Misra)
(7/n) ‘Through the lens, into the cell’
Microscopy is a powerful tool to understand the cellular world at a micron-scale (1/1,000,000th of a meter!). The use of any microscope depends on its ability to magnify and clearly distinguish two closely spaced points in space (resolution). These two parameters are governed by incident light and the optical components – in short, physics.
But what if one could enlarge the sample in a way that allows us to probe into more details?
In a technique called expansion microscopy, samples can be enlarged prior to imaging by transferring them onto a hydrogel, followed by expansion of the gel via hydration. One could compare the pre-enlarged sample to a rubber balloon which is yet to be inflated. The structure becomes larger and less dense once inflated, enabling one to see more details on the surface of the balloon more clearly. Dense structures inside a cell, which would otherwise be indiscernible with the physical limits of microscopy, can now be imaged after enlarging the sample, gently, with an expandable hydrogel.
Pictured in this image, captured by Sinjini Ghosh (graduate student in Aprotim Mazumder’s lab), is an expansion microscopy image of a human osteosarcoma U2OS cell stained for β tubulin, a component of the cytoskeletal structures – microtubules. Expansion microscopy allows her to increase the magnification by almost 4.5x, making visualization of the cytoskeletal tracks easier.
Image: Sinjini Ghosh
Description: Snigdha Nadagouda
(6/n) ‘Coarse grain model of amyloid beta proteins’
The aggregation of amyloid beta proteins is a characteristic marker of Alzheimer’s disease. In the accompanying image, we see a snapshot of a simulation where rod-shaped particles (spherocylinders) represent and behave like a disordered protein — amyloid beta. The clumping of this protein is associated with Alzheimer’s disease and hence, understanding the dynamics of this aggregation is crucial to trace the underlying biology of this disease condition. Scientists with expertise in computational sciences are trying to model how amyloid beta ends up forming clumps. However, the interplay of multiple forms of these proteins, its interaction with other biochemical entities, and its long aggregation time results in a problem so complicated that it cannot be addressed by conventional computational methods. Things are further complicated as the protein does not fold properly and its structure is unknown.
Simple descriptions often help arrive at elegant descriptions of unanswered scientific problems. This image by Yatharth Bhasin (Junior Research Fellow at Kanchan Garai’s lab) is a coarse grain model of how multiple amyloid beta proteins may interact with each other. The coarse grain model isolates the most important details of the system that are crucial for aggregation, without pondering on the detailed geometry of the protein. Each amyloid beta protein is represented by a spherocylinder. The orange regions on the spherocylinder highlight portions of the protein that are interactive in nature, while the blue regions are passive. A combination of these different regions on the macromolecules model how multiple proteins come together and aggregate.
While interdisciplinary approaches begin to give some clues of how amyloid beta proteins clump, we have only scratched the surface of this intriguing problem.
Simulation, Custom Render and Description: Yatharth Bhasin
(5/n) ‘The shapeshifting powerhouses’
Mitochondria are tiny molecular machines inside cells that generate energy to power the biochemical reactions essential to life. While most textbooks accord an elliptical shape to mitochondria, they happen to be extremely dynamic in shape, structure and number when observed in live cells.
Besides generating energy, they are also hubs of several cellular pathways and characteristic patterns of mitochondrial dynamics are seen during different stages of cellular development.
Aravind H (graduate student in Manish Jaiswal’s lab) has acquired an image of a cross section of the fruit fly (Drosophila) testis. This section has cells in the later stages of sperm development. The image shows different clusters of mitochondria, the varying shapes showing the patterns in which they are distributed in different cells. Since sperms require a lot of energy for propagation, they are usually packed with mitochondria. Insect cells are known to have some of the longest sperms (up to a few centimetres) with mitochondria distributed throughout their entire lengths which makes it easier to visualize these extremely tiny organelles. Here, Aravind has used flies where the outer mitochondrial membrane protein Tom20 is labelled with a fluorescent tag that lights up when light of a particular wavelength is shone on them, delimiting the structures. All the glowing golden structures seen in the image are due to the fluorescent protein representing mitochondria expressed in different patterns in cells. The numbers in the image denote the developmental stages in order from 1 to 7, each a stage showing a particular pattern of mitochondrial distribution. In (1), the hollow structures depict cell nuclei with a ring of mitochondria surrounding it. The mitochondria are then seen changing shape in actively dividing cells (2). They condense (3), stretch out (4) and ultimately form the long threadlike stretches in mature sperms (5-7), running down their entire lengths. Here, one gets to see a range of shapes and structures that mitochondria can exist in, breaking the stereotypical elliptical image that we have of them in mind.
Image: Aravind H
Description: Shravasti Misra
(4/n) ‘Cellular tunnels enabling long distance communication’
One of the interesting ways by which cells communicate with each other, especially across a void separating two masses of cells, is via tunneling nanotubes. These nanotubes are thin extensions of the cell membrane that connect the cell patches together, similar to a long tunnel connecting two separate regions.
In this video captured by Piyush Daga (graduate student in Tamal Das’s lab), we see patches of skin cancer cells connected by one such nanotube through which mitochondria, the powerhouses of cells, are being transferred. These tubes also aid in transfer of several cellular components including proteins, RNAs, viruses and other organelles.
Video and description:
(3/n) ‘Thwarting malarial invasion’
Mosquito bites, apart from being itchy and annoying, are a means of infection transfer for many diseases like malaria and dengue. Plasmodium falciparum, the causative agent of malaria, has two hosts – mosquitoes and humans.
During the later half of its life cycle, P. falciparum invades red blood cells (RBCs) in the human host. The parasite forms tight junctions with the RBC, the formation of which establishes the commitment to invasion.
In this image, Akash Narayan (graduate student at Kalyaneswar Mandal’s lab) has captured the characteristic ring stage morphology of the parasite which forms shortly after the parasite has invaded the RBCs. He is presently working towards identifying novel peptides that would prevent P. falciparum from forming tight junctions with RBCs, and consequently thwart the invasion by the malaria parasite. The image, shown here, is used to quantify the extent of RBC invasion by parasites. One could also study such images to see how effective candidate peptide drugs are – are they able to prevent the parasites from entering the RBCs?
Image: Akash Narayan
Description: Snigdha Nadagouda (with inputs from Akash Narayan)
(2/n) Powering a battery
Inside the batteries that have transformed our world, there exists a beautiful chimeric world of topologies. The image, acquired using Scanning Electron Microscopy, captures a unique smorgasbord of nano-sized components functioning as a catalyst inside a lithium air battery. This catalyst, developed by Pallavi Thakur (graduate student in T. N. Narayanan’s lab), consists of amorphous sheets of nitrogen doped carbon that envelope an orb-like cluster of iron carbide and carbon nano-spheres.
The complex but intriguing morphology of this catalyst makes it highly porous which allows it to store lithium peroxide (Li2O2), the final discharge product. The catalyst facilitates the chemical processes required to store and release energy. The iron, along with nitrogen and carbon, helps break down Li2O2 into lithium, overcoming excess external energy requirements to charge the battery after all the energy in it is used up.
Thus, the carbon and iron based dual-functioning catalyst plays a crucial role in increasing the efficiency and durability of lithium air batteries. With an advantage of being cost-effective, this catalyst can help us move towards more sustainable sources of energy in future.
(1/n) ‘The nerve of this fly!’
The image shows a fruit fly neuron making an active synapse with an abdominal muscle, forming a neuromuscular junction. The axon of the neuron is labelled in green, while the axon terminals of the neuron (axon terminals are involved in forming synapses – with other neurons or with muscles) are labelled in red.
The labelling was done using fluorescent dyes attached to antibodies. These antibodies can bind to specific proteins present in these neurons at the neuromuscular junctions and aid in visualization of those proteins when viewed under a microscope. The yellow label highlights regions where the proteins of interest overlap.
This image was captured by Sunayana Sarkar (graduate student in Manish Jaiswal’s lab) who was looking at how synaptic connections at neuromuscular junctions can be increased or decreased by regulating growth and proliferation-associated genes in fruit fly larvae.
Image: Sunayana Sarkar
Description: Padmapriya Shankar Iyer
Editor: Anusheela Chatterjee