Emergent Biological Systems (Dr. Siddharth Deshpande)
The philosophy of EmBioSys lab
Living systems are an ensemble of countless emerging properties, manifested at cellular, organismal, and population level. It is the self-assembly and self-organization of biomolecules – from amphiphilic lipids forming cell membranes to complementary DNA strands joining together to form an obviously useful genetic code – into a highly functional and complex system that make cells spring to life. Understanding these phenomena is what makes biological soft matter exciting to us. Since cells are so complex, we have a strong liking for bottom-up biology, i.e., studying purified cellular components in a controlled manner. Such minimalistic approach helps to pinpoint cause-effect relationships, but also to design bio-inspired, minimal functional modules – and take a step closer towards synthetic cells!
Key recent publications
- Mart G. F. Last, S. Deshpande and C. Dekker. pH-controlled coacervate-membrane interactions within liposomes. ACS Nano, 2020.
- S. Deshpande and C. Dekker. Synthetic life on a chip. Emerging Topics in Life Sicences, 2019.
- S. Deshpande et al. Spatiotemporal control of coacervate formation within liposomes. Nature Comunications, 2019.
- S. Deshpande and C. Dekker. On-chip microfluidic production of cell-sized liposomes. Nature Protocols, 2018.
We are an international team of enthusiastic scientists with diverse backgrounds. We do interdisciplinary research combining biology with chemistry and physics, while extensively using on-chip microfluidic technology. Following are our key research areas:
Understanding cellular morphogenesis in 3D environments
Amongst a rich diversity of emergent properties cells exhibit, we are currently focussing on the ability of cells to change shape and move, in response to intracellular and extracellular stimuli. Eukaryotic cells do so using a dynamic intracellular protein machinery known as the cytoskeleton, and we are particularly interested in the polymorphic actin filaments. Using purified protein components and OLA, an on-chip liposome production technique that we have developed, we wish to understand, for example, blebbing motility exhibited by cells in 3D environments.
Impact of intracellular organization on cytoskeletal dynamics
Impact of intracellular organization on cytoskeletal dynamics intracellular compartmentalization is an essential feature of eukaryotic cells, in order to perform and regulate biological functions. Even so, their impact on actin dynamics is highly unexplored, especially using minimal in vitro systems. Two prominent examples are the stiff, bulky nucleus and the numerous membraneless organelles (biomolecular condensates) found inside cells. We wish to study the impact of these compartments in actin-based morphogenesis using suitable microfluidic systems such as condensate-in-liposome structures that we recently developed.
Developing soft matter-based biosensors
Rapid diagnosis is key to ensuring optimized treatment of diseases. Biosensing techniques, however, can be quite slow to perform, often requiring specialized laboratory equipment or technicians to interpret. We want to probe the potential of liquid crystals to exhibit a clear and rapid optical response in presence of biomarkers (antibodies, toxins, etc.). By harnessing their unique ability to exhibit crystalline ordering and birefringence, our goal is to produce a liquid crystal-based biosensor capable of rapid in situ detection of biomolecules. We would ultimately like to prototype a lab-on-a-chip diagnostic test that can be used on-field by a non-expert.
Developing microfluidic technologies
As an experimentalist, one wants maximum control over your system, in order to systematically and reproducibly tackle the problem. Microfluidic is a versatile technology that offers such a well-defined and controllable environment. Over the years, we have developed numerous microfluidic assays to tackle important biological questions: Quasi-2D microchambers to study biochemical reactions, flow-assays to understand the surface-sensing mechanism in bacteria, bubble-blowing machines to make cell-mimicking vesicles, etc. We extensively utilize these on-chip tools as well as design new ones.
Offered MSc and BSc projects
Membraneless multi-compartmentalization in synthetic cells
Biosensing using Cholesteric Liquid Crystals
Interactions and emergent behavior of biomimetic vesicles within confinements and flows
Assembling a minimal, functional actomyosin cortex inside liposomes
Designing novel cell-mimicking containers using microfluidics
Studying the dynamics of cytoskeletal polymers in membraneless compartments