Project Title: Simulations of swimming, sensing and steering in sperm Project Number IMURA0708 Monash Main Supervisor (Name, Email Id, Phone) Dr. Prabhakar Ranganathan, [email protected], Full name, Email Monash Co-supervisor(s) (Name, Email Id, Phone) Monash Head of Dept/Centre (Name,Email) Prof. Chris Davies, [email protected] Monash Department: Mechanical & Aerospace Engineering Monash ADRT (Name,Email) Prof. Ana Deletic, [email protected] IITB Main Supervisor (Name, Email Id, Phone) IITB Co-supervisor(s) (Name, Email Id, Phone) IITB Head of Dept (Name, Email, Phone) Prof. Sameer Jadhav Full name, email Full name, email Full name, Email Full name, Email Prof. K. V. venkatesh Full name, email IITB Department: Research Clusters: Research Themes: Highlight which of the Academy’s CLUSTERS this project will address? Highlight which of the Academy’s Theme(s) this project will address? (Please nominate JUST one. For more information, see www.iitbmonash.org) 1 Material Science/Engineering (including Nano, Metallurgy) 2 Energy, Green Chem, Chemistry, Catalysis, Reaction Eng 3 Math, CFD, Modelling, Manufacturing 4 CSE, IT, Optimisation, Data, Sensors, Systems, Signal Processing, Control 5 Earth Sciences and Civil Engineering (Geo, Water, Climate) 6 Bio, Stem Cells, Bio Chem, Pharma, Food 7 Semi-Conductors, Optics, Photonics, Networks, Telecomm, Power Eng 8 HSS, Design, Management (Feel free to nominate more than one. For more information, see www.iitbmonash.org) 1 Advanced computational engineering, simulation and manufacture 2 Infrastructure Engineering 3 Clean Energy 4 Water 5 Nanotechnology 6 Biotechnology and Stem Cell Research The Research Problem Mammalian sperm cells must swim through the narrow, convoluted and mucus-laden oviduct to locate an egg and fertilise it. These cells are guided by fluid flow and chemical and thermal cues towards the egg: exactly how they manage to achieve this is a mystery. Understanding this is important because about one in twenty men, and some 30-50% of infertile couples use assisted reproduction technologies (ARTs). The natural process by which sperm cells develop makes their DNA highly susceptible to damage. The treasurehunt game in the oviduct is designed to select a healthy winner healthy capable of sensing all the complex signals to swim successfully to the egg. However, the most popular ART used at present is Intracellular Sperm Cytoplasmic Injection (ICSI) in which genetic material is directly transferred from a sperm into an egg. Studies are now showing that this drastic interference has serious long-term consequences for the health of IVF children. Understanding how sperm sense signals and steer towards the egg could lead to improved ARTs that select healthy sperm. Besides couples seeking IVF treatment, such improvements could also benefit livestock breeding and agriculture, and conservation of species that do not breed well in captivity. There is an engineering motivation as well. The goal of microfluidic technology is to shrink fluid processes to achieve labs-on-chips. But if you walk into any microfluidics laboratory today, you will find that all the desk space is taken up by paraphernalia required to achieve pumping and mixing within microfluidic devices: we have chips-in-labs, as opposed to labson-chips! A sperm cell effectively pumps fluid past itself to move forward. By explaining how sperm manipulate the fluid around them to achieve steering, we could one-day design of microfluidic filament-driven pumping and mixing. Project aims Fig. 1: (A) Hyperactive flagellar beating observed in experiments; coloured curves are centrelines extracted by image-analysis. (B) Typical mammalian sperm cell (C) Fine structure of the axoneme “engine” Our aim is to use computer simulations to explain sperm navigation. Sperm swim by “beating” tails called flagella (Fig. 1 A & B). The flagellum is driven by the most complex engine known, the axoneme (Fig. 1 C). There is little doubt that beating fundamentally originates in the axoneme, but the source of complexity in beat patterns remains a mystery. The net propulsive thrust and swimming trajectory depend on the beating pattern. The internal biochemistry must act to modify the beat pattern to adjust trajectory curvature and steer towards a chemical signal. Without knowledge of the mechanism that regulates beat patterns, we cannot understand sperm swimming. A symmetric beat pattern will only lead to linear trajectories on average. An asymmetry must be induced in the pattern to execute a turn. Our simulations will study how the cell controls its beating and manipulates the fluid around to control its swimming direction in response to chemical signals Expected outcomes The Project will deliver a detailed mathematical model of a sperm cell and its interaction with the surrounding fluid. Fluid-structure problems are among the most complex problems in fluid dynamics. This project will train you in advanced numerical and computational techniques for studying such interactions. An open-source simulation package – the Virtual Sperm -- will be developed. This Project is a part of an exciting collaboration between sperm cell biologists and engineers at IITB and Monash. You will work with biologists to understand biochemical signaling in sperm and translate that into mathematical language. You will interact with engineers setting up experiments to measure the threedimensional motion of a single sperm cell and the fluid around it, to compare simulation predictions with experiments. The Project is a perfect springboard for a career in modeling and simulations in microfluidics, and cellular mechanobiology. How will the project address the Goals of the above Themes? The Project involves mathematical modelling and aims to develop a sophisticated simulation tool that will enable exploring sperm cell biology. It therefore satisfies the goals of the themes of “Advanced Computational Engineering, Simulation, and Manufacture” and “Biotechnology and Stem Cell Research”. Capabilities and Degrees Required To be selected on this Project, you will need to demonstrate a firm understanding of fluid and solid mechanics, and standard numerical techniques for solving the ordinary and partial differential equations that arise in mechanics. This will include topics such as mass, momentum and energy conservation, the stress tensor, Hooke’s Law, Newton’s Law of Viscosity, the Navier-Stokes equations, the Reynolds number, similarity analysis, vector calculus in Cartesian, cylindrical-polar and spherical co-ordinate systems, surface and volume integrals in these co-ordinate systems, finite-difference methods, and the Crank-Nicholson method. Experience in code development in the context of mathematical modelling of physical phenomena will be a plus, although not essential. Students with an undergraduate or masters degree in physics, mechanical or chemical engineering are ideal. Applied mathematicians with a strong understanding of fluid and solid physics will also be considered. Collaborators The Project is a collaboration between Prof. Sameer Jadhav and Prof. Prabhakar Ranganathan. Select up to (4) keywords from the Academy’s approved keyword list (available at www.iitbmonash.org) relating to this project to make it easier for the students to apply. CFD, simulation, microfluidics
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