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Molecules of Life & Mutations

Předmět na Lékařská fakulta v Plzni |
EAV030X04

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In collaboration with prof. Siegfried Schwarz, M.D., Division of Experimental Pathophysiology & Immunology, Biocenter, Innsbruck Medical University, CCB, Innrain 80-82, 6020 Innsbruck, Austria, siegfried.schwarz@i-med.ac.at

We would like to welcome undergraduate students of Medicine as well as Biology, from the 3rd semester onwards, including PhD students. You are going to learn molecular modelling methods, perform your practical training in the computer room and deliver an individual homework. This homework will be presented in a final 10-minutes presentation in English after the 3-day interactive and interdisciplinary course. On the last day of the course (after at least 2 weeks), students are going to present their homework in front of all attending colleagues including teachers. As such, everybody learn from the others - kind of a multiplication effect.

This course gives you a general overview on our understanding of the normal as well as abnormal protein structures originating from particular gene mutations and/or allosteric effector function in health as well as in a diseased state. Introduction provides couple of examples of structure-function relationships in human medicine.

Next day we follow with a hands-on course in a computer room where attendees receive a detailed step-by-step description how to perform practical molecular modelling on PC using appropriate open-source software (PyMol).

Having the X/Y/Z coordinates of atoms, as deposited in the Brookhaven Protein Data Bank (PDB), students can visualize and manipulate 3D structures of crystallized proteins, alone or after interaction with small or large ligands such as their substrates, drugs, DNA or other proteins.

Attendees will learn also how to use the OMIM (Online Inheritance in Men) Data Bank from where they can retrieve the published mutations and a corresponding disease pathology. Thereby, various structural characteristics can be recognized: domains of certain structure or charge, hydrophobicity or shape and other properties, which can serve e.g. as a ligand-binding domain, a DNA-binding domain, a drug-metabolizing pocket or as a domain for any other biological function. The real power of molecular modelling resides in its informative value displaying the molecular structure, in total or in portions thereof, in different formats such as wireframe, protein backbone, atoms, overall surface etc. It is possible to turn the molecule in all directions and to see in real time various aspects of its structure. Most importantly, points of mutation, as documented in the OMIM and other databases, can be mapped into a structural model in order to understand which function of the protein would thus be altered and whether this change in structure would result in loss-of-function or gain-of-function showing recessive or dominant effect. Link between arginine vasopressin precursor (AVP) and Diabetes insipidus serves as an illustrative and informative example.

In the second part of this course, students will get assigned an individual mutated protein and a corresponding disease pathology that they have to elaborate as a homework according to the demo example they have seen in the course. Each student should prepare a short (10 minutes) lecture in Power Point or alternatives and discuss her/his observations, published data and clinical outcomes.

The course is based on a textbook published by Siegfried Schwarz: MOLECULES OF LIFE & MUTATIONS (Karger, Basel 2002, ISBN: 978-3-8055-7395-5), in which structures of 150 most important molecules are displayed. http://www.karger.com/Book/Home/227359

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Designed by Professor Siegfried Schwarz, Medical University Innsbruck/Austria and Professor Jiri Hatina, Faculty of

Medicine in Pilsen

Condition for registration passing the exam in Biology.

A practical computer course: molecular modelling and disease explanation - pathophysiology in endocrine, neural and immune systems. The course will help you to understand a disease in correlation with molecules, their mutations, and specific drugs while performing database searches and molecular modelling on your own. Here, we use only public domain resources you might be able to exploit in your everyday practice.

Please, enroll to e-learning in Moodle: https://dl2.cuni.cz/course/view.php?id=2266 using your CAS account.

Program:

April 8th-10th, 2019 in Prague

Practical training days in the PC room for an introduction to molecular modeling software and how to use PDB and

OMIM databases. Computers provided, your personal comps allowed.

It includes an assignment of a single disease case report to each student for your homework on linking the protein structure to the underlying molecular pathophysiology.

Later: your presentations online we will agree upon the proposed term followed by the receipt of credits. A consensual decision on the date of final case report presentations of your homework will be taken on April, 10th.