PhD courses at University of Copenhagen

Advanced methods for solving high-resolution structures of membrane proteins
Provider: Faculty of Health and Medical Sciences

Activity no.: 3272-24-00-00
	Enrollment deadline: 30/09/2024

Date and time	21.10.2024, at: 08:30 - 25.10.2024, at: 18:00
Regular seats	18
Course fee	14,160.00 kr.
Lecturers	Claus Løland
ECTS credits	4.20

Contact person	Lucy Holt E-mail address: lucy.holt@bio.ku.dk

Enrolment Handling/Course Organiser	PhD administration E-mail address: phdkursus@sund.ku.dk

Aim and content This course is free of charge for PhD students at Danish universities (except Copenhagen Business School), and for PhD Students from NorDoc member faculties. All other participants must pay the course fee. Anyone can apply for the course, but if you are not a PhD student at a Danish university, you will be placed on the waiting list until enrollment deadline. This also applies to PhD students from NorDoc member faculties. After the enrollment deadline, available seats will be allocated to applicants on the waiting list. Intended learning objectives Students will gain knowledge and insight into practical and theoretical aspects of state-of-the-art technical advances within structural biology. This understanding will specifically focus on techniques relevant for solving membrane structures. A student who has met the intended learning objectives of the course will be able to: 1. Knowledge of and insight into practical and theoretical aspects of cutting-edge technical advances within structural biology which are relevant for solving membrane structures 2. Skills in sample preparation, protein quality and activity, acquisition and interpretation of structural data, data presentation and method limitations and advantages. 3. Competences on how to integrate the acquired relevant techniques for solving membrane protein structures within their own projects. 4. Obtain knowledge about recent advanced techniques employed to solve membrane protein structures and the opportunity to discuss the methods and approaches with the invited responsible professors. 5. Developing intellectual agility, ability to see potential in ideas, and build the capacity to expand through critical thinking and problem solving as part of their current project and beyond. Content The students will obtain insights into the methods required for obtaining a high-resolution structure of a membrane protein. This will include (1) lectures with theoretical description of methods, (2) practicals where the students get acquainted with the required procedures including hands-on sessions, (3) round-table discussion and presentation of key scientific papers together with the invited authors, and a poster presentation at the seminar concluding the course. Integral membrane proteins are notoriously difficult to work with. The yield when purified can often be 1/100 of a typical soluble protein. The delicate structure and required detergent often result in a short functional lifetime for the protein outside the cell membrane. This makes them challenging for structural studies using protein crystallography where incubation times of days to weeks can be required for the crystal lattice to form. Accordingly, single molecule cryo electron microscopy (cryo-EM) has revolutionized the structural field for membrane proteins, awarding the developers the Nobel prize in 2017. In the course lectures, the students are introduced to methodologies such as: - How to stabilize membrane proteins in a detergent-free environment using amphipathic helices or polymers to create a lipidic microenvironment around the protein: the nanodisc. - Introducing the theory behind single molecule cryo-EM. Its strengths and limitations and the basic requirements for obtaining a high-resolution structure. - Serial synchrotron crystallography (SSX) as an alternative to cryo-EM. This emerging technique can be used to determine the noncryogenic crystal structure of macromolecules while minimizing radiation damage. - Ways to determine whether the protein is functional after undergoing extraction from the membrane environment and into either detergent micelles or nano discs. - The use of G-protein coupled receptors (GPCRs) as case for structural information. This includes a description of the conformational states and the challenges in ‘locking’ the proteins in specific states. The practical exercises will provide insight into: - How to express and purify a protein. Introduction to expression platforms and ways to introduce your gene of interest. When the protein is expressed, options to isolate the desired protein form the cells are shown. - How to convert the cryo-EM data of protein particles to a high-resolution 3D model. This session also includes a site visit at Center for Integrated Microscopy (CfIM). The workshop will include: - A journal club. Here the students get to prepare and present a scientific paper. The papers describe state-of-the-art structural analysis performed by internationally renowned professors. - A round table discussion with the professors who authored the papers. The symposium will include: - Lectures on integrative approaches to structural biology by internationally renowned professors. - Poster session where all participants will be expected to present a poster. Participants The course is an advanced interdisciplinary course and students interested in biological structure are encouraged to apply from a wide variety of disciplines, including chemistry, biochemistry, biology, physics, computer science, human biology, neuroscience, and the pharmaceutical sciences. Students will be expected to have some basic knowledge of structural determination and/or protein science. Relevance to graduate programmes The course is relevant to PhD students from the following graduate programmes at the Graduate School of Health and Medical Sciences, UCPH: Neuroscience Molecular Mechanisms of Disease Pharmaceutical Sciences (Drug Research Academy) Language English Form Lectures, experimental work, group work, presentations, round table discussions, poster presentations. Course director Professor Claus J. Løland, Department of Neurosciencen, cllo@sund.ku.dk Teachers Professor Claus J. Løland, Department of Neuroscience Associate Professor Nicholas Taylor, Center for Protein Research Associate Professor Henriette Autzen, Department of Biomedical Sciences Associate Professor Azadeh Shahsavar, Department of Drug Design and Pharmacology Associate Professor Karen Martinez, Department of Chemistry Professor Mei Hong, Massachusetts Institute of Technology Professor David Drew, Stockholm University Professor Arne Elofsson, Stockholm University Dates 21 - 25 October 2024 Course location Panum building, SUND. Registration Please register before 30 September 2024 Expected frequency This course is a once-off. Seats to PhD students from other Danish universities will be allocated on a first-come, first-served basis and according to the applicable rules. Applications from other participants will be considered after the last day of enrolment. Note: All applicants are asked to submit invoice details in case of no-show, late cancellation or obligation to pay the course fee (typically non-PhD students). If you are a PhD student, your participation in the course must be in agreement with your principal supervisor.