Multiscale approaches to study the biophysics of parasites and plankton

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Abstract/Contents

Abstract
Multi-scale interactions of motile microorganisms with their environment are crucial in understanding disease transmission, as well as the ecology and biophysics of our oceans. This theme underlies the two problems I tackle in this thesis. The first part of the thesis is focused on the schistosomiasis parasite which currently infects 200 million people world-wide, with 700 million more at risk. Infection occurs when the free-living, motile stage of the parasite known as cercariae swim through fresh-water and infect human hosts by penetrating the skin. The swimming motility of cercariae is therefore crucial to disease transmission but is not well understood emphasizing an urgent need for research efforts. Towards this I combined biological experiments, with robotics and mathematical models to uncover how cercariae use their unique forked-tail to generate a robust and efficient "T-swimmer" swimming gait. Further I discuss results from our model and experiments which point to specific degrees-of-freedom that cercariae create that are crucial for their swimming efficiency, suggesting novel drug-targets for disrupting host-seeking. Studying schistomiasis cercariae in their native, ecological setting of ponds, rivers and lakes in Madagascar revealed an unsolved experimental challenge in studying such multiscale problems in the lab. Significantly, this challenge is also present in studying microscale biophysical processes in the ocean: how to measure single cells and organisms, at microscale resolution, while allowing them to freely move over ecological-scales (hundreds of meters) along the axis of gravity? To address this, I invented "Scale-free Vertical Tracking Microscopy", based on a "hydrodynamic-treadmill for single cells" with no bounds for motion along the axis of gravity. Using this method to bridge spatial-scales, I assembled the first multi-scale behavioral dataset of freely-swimming planktonic cells and organisms. Using this tool, I also demonstrate a "virtual-reality system for single cells",  wherein cell behavior directly controls its ambient environmental parameters and vice versa, enabling novel quantitative behavioral assays. The microscopy platform is built using open-source hardware and software components and has further been deployed in field settings such as marine stations in Puerto Rico, Monterey as well as oceanic research-vessels. This ability to bring the lab to the ocean has resulted in new discoveries such as rapid buoyancy modulation over millisecond timescales in planktonic diatoms as well as discovering gravity-oriented swimming behaviors among 8 phyla across the tree-of-life. This microscope and the results presented, exemplify a new paradigm of multi-scale measurement wherein one can observe macroscale, ecologically relevant phenomena at microscale resolution.

Description

Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource.
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2020; ©2020
Publication date 2020; 2020
Issuance monographic
Language English

Creators/Contributors

Author Deepak Krishnamurthy
Degree supervisor Lele, Sanjiva K. (Sanjiva Keshava), 1958-
Degree supervisor Prakash, Manu
Thesis advisor Lele, Sanjiva K. (Sanjiva Keshava), 1958-
Thesis advisor Prakash, Manu
Thesis advisor Wang, Bo, (Researcher in bioengineering)
Degree committee member Wang, Bo, (Researcher in bioengineering)
Associated with Stanford University, Department of Mechanical Engineering

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Deepak Krishnamurthy.
Note Submitted to the Department of Mechanical Engineering.
Thesis Thesis Ph.D. Stanford University 2020.
Location electronic resource

Access conditions

Copyright
© 2020 by . Deepak Krishnamurthy
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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