636-0008-00L  Nanomachines of the Cell (Part II): Engineering and Application

SemesterSpring Semester 2016
LecturersD. J. Müller
Periodicityyearly course
Language of instructionEnglish
CommentPrerequisites: Students should have an interdisciplinary background (bachelor) in molecular biotechnology, biochemistry, cell biology, physics, bioinformatics or molecular bioengineering.


AbstractThis second part of the lecture series "Nanomachines of the Cell" extends what has been learned in the first module. "Engineering and application" will be thus a consolidation of the concepts of functional biomolecular units of the cell as nanoscopic machines. The specific aim is to be able to use these cellular machines in more complex biotechnological processes as nanoscale functional elements.
ObjectiveGain of an interdisciplinary research and development competence which qualifies for scientific work (master`s or doctoral thesis) as well as for work in the research and development department of a biotechnological company. The module is of general use in nano- and biotechnological courses of study focusing modern biomolecular technologies.
ContentAssembly of fibrillar structures. Filamentous structures inside and outside the cell. Principles of polymerisation dynamics: Nucleation, polarity, equilibrium and non-equilibrium driven polymerization, treadmilling, energy consumption, asymmetric building blocks, ... Self-assembly processes in polymer chemistry and physics. Self-assembly processes into two- and three-dimensions. Filaments of the cell: F-actin, intermediate filaments, microtubuli, and collagen. Filaments of the cell fulfil several functions: Structural integrity and functionalization of the environment. How does the cell control these functions? Example: The collagen family. Molecular and supramolecular structure of collagens. On the importance of motifs on the molecular packing mechanism of collagen. Occurrence of collagens and functional roles. Diseases related to collagen malfunction. Properties of collagen: Flexibility, elasticity, strength, persistence length, conformations, binding sites, signal transduction, ... Proteins that functionalize collagens. Can we use these proteins as a biomolecular toolbox to build up three-dimensional functional scaffolds? Directing and controlling the self-assembly of collagen type I. Learning which factors determine the supramolecular structure of self-assembled collagen. Using this knowledge to guide the self-assembly of collagen into nanoscopic scaffolds. Creating intelligent collagen scaffolds to guide cellular functions. Ways to functionalize collagen matrices for their use in biotechnology and tissue engineering. The great challenges: How can we create three-dimensional collagen scaffolds?
DNA origami. Using DNA to build artificial three-dimensional structures at nanometer precision. From smilies to mechanical building blocks to three-dimensional containers almost every three-dimensional structure can be build. Self-assembly process of DNA. 'Programming the DNA': How to engineer the DNA sequence to promote it's self-assembly into a three-dimensional structure. How to engineer the DNA sequence to promote the self-assembly of the DNA into a precise three-dimensional nanoscopic arrangement. Engineering lessons: How to functionalize three-dimensional DNA containers so that they have a different fluorescent protein on each corner? How to functionalize a functionalize three-dimensional DNA container so that it frees its cargo on response to an external stimuli? How to functionalize a three-dimensional DNA container so that a cell can opens it and extract the cargo? Where may DNA origami be in 10 years? Comparative approaches using peptides to design origami.
Microtubuli. Occurrence, structure, function, and properties. Cell mechanics, motility and dynamic. Mitosis. Cargo transport by motor proteins. Assembly mechanisms, tubulin subunits, nucleation, polarity, kinetics, concentration dependent growth, GTP dependency, dynamic instability, capping, ..). Designing three-dimensional structures using microtubuli. Creating a racing track: Motility assays. Designing and microstructuring of supports as circuits for molecular shuttles. Biofunctionalization of the circuits. Transporting molecular cargo along circuits. Engineering molecular devices to switch the transport 'on' and 'off'.
Motor proteins. Introduction: Translational motors, rotary motors, chemical driven motors, light-driven motors, unidirectional and bidirectional motors, reversibility, molecular ratchets, future visions. Example of rotary motors: F-ATP synthase and flagella motor. F-ATP synthase was introduced in (Nanomachines of the cell Part I). Common and different engineering principles of the F-ATP synthase and the flagella motor. Structure, function, energy source, and rotational modes. Controlled assembly of a complex machinery such as the flagella motor. Are there ways to exchange the building blocks of the motor and to 'tune' it?
Motor proteins of the cytoskeleton.
iViruses.
Prediction, design und engineering of cellular machines.
Lecture notesHand out will be given to students at lecture.
LiteratureAlberts et al: Molecular Biology of the cell

Biochemistry (5th edition), Jeremy M. Berg, John L. Tymoczko, Lubert Stryer; ISBN 0-7167-4684-0, Freeman

Principles of Biochemistry, Nelson & Cox; ISBN: 1-57259-153-6, Worth Publishers, New York

Cell Biology, Pollard & Earnshaw; ISBN:0-7216-3997-6, Saunder, Pennsylvania
Intermolecular & Surface Forces, Israelachvili; ISBN: 0-12-375181-0, Academic Press, London

Proteins: Biochemistry and Biotechnolgy, Walsh; ISBN: 0-471-899070, Wiley & Sons, New York

Textbook of Biochemistry with Clinical Correlations, Devlin; ISBN: 0-471-411361, Wiley & Sons, New York

Molecular Virology, Modrow et al.; ISBN: 3-8274-1086-X, Spektrum Verlag, Heidelberg
Prerequisites / NoticeStudents should have an interdisciplinary background (bachelor) in molecular biotechnology, biochemistry, cell biology, physics, bioinformatics or molecular bioengineering.

The module is composed of 3 SWS (3 hours/week): 2-hour lecture, 1-hour seminar. For the seminar, students prepare oral presentations on specific in-depth subjects with/under the guidance of the teacher.