Course Syllabus
Microbrains Lab: Modeling Neurodegeneration |
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Draft syllabus
| Semester & Location: |
Summer 2020 - DIS Copenhagen |
| Type & Credits: |
Summer Lab & Research Session - 6 credits |
| Major Disciplines: |
Biology, Biomedicine / Biotechnology, Neuroscience |
| Prerequisites: |
One year of biology and one course in either molecular biology or genetics, all at university level. |
| Faculty Member: |
Kristine Freude |
| Program Director: | Susana LS Dietrich - sd@dis.dk |
| Time & Place: |
Wet lab component: University of Copenhagen |
Faculty
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Kristine Freude, Associate Professor PhD at Max Planck Institute for Molecular Genetics and Free University, Berlin, Germany in Human Genetics (2005). Postdoctoral Research Fellow at UC Irvine, CA, USA (2005-2011) Postdoctoral Researcher (2012-2014) University Copenhagen. MSc at Robert Koch Institute and Free University, Berlin, Germany, in 2001 working with Mycobacteria. Assistant Professor (2014-2015) University Copenhagen. Associate Professor (2015-present) University Copenhagen. With DIS since 2016. |
Course Description
In our aging society more and more people suffer from neurodegenerative diseases such as Alzheimer’s disease (AD). Decades of research have focused on mouse models, but all drug candidates which have successfully treated AD in mice have failed in human clinical trials. In order to address these pressing needs, human models such as neurons, astrocytes, and microglia derived from induced pluripotent stem cells are the key. In combination with gene editing using CRISPR-Cas9 these cellular models provide insights into early disease development and progression in the species we need to investigate: humans.
You can find an example of our work here: iPSC Model of Frontotemporal Dementia.pdf
Expected Learning Outcomes
- To employ the concepts of stem cell research and to discuss how those can be used as disease models
- To understand, perform and evaluate reprogramming of adult cells into induced pluripotent stem cells (iPSC)
- To employ, design and evaluate different methods of directed differentiation towards the major cell types of the human brain
- To demonstrate, perform and evaluate CRISPR-Cas9 mediated gene editing into iPSC
- To develop a critical understanding of ethical implications of this line of research
- To learn the ability to evaluate and criticize experimental evidence in scientific papers
- To learn how to produce and monitor report laboratory experiments
- To be able to produce a feasible research proposal regarding stem cells and disease modeling
Approach to teaching
The students will experience a very hands on class. Students will be provided with the basic scientific knowledge of the field and be introduced to the methods needed to conduct the experiments. Regarding teaching style, especially in the laboratory setting, the approach is "learn by doing". For the theoretical parts students are expected to immerse themselves in the topic and take responsibility so they achieve the highest learning outcome by actively participating in our discussions and in their presentations. There will be several activities, which will be interactive, including role playing in our ethical sessions.
Expectations of the students
During the theoretical part students are expected to actively participate in discussions and critically evaluate the research and ethical components within the field. During the practical part students are expected to engage and carefully monitor and report the conducted experiments in the lab books. Moreover students are encouraged to critically evaluate possible issues if experiments do not go the way they should, and suggest modifications to experiments or reflect on potential mistakes. Overall the most important part is being enthusiastic about the science and active participation in the form of questions, discussions and critical thinking.
Wet Lab/Lab work
The course will have 3/4 practical hands on lab experience. Here the students will learn how to culture iPSC, genetically modify them using CRISPR-Cas9, perform directed differentiation into neurons, astrocytes and microglia in 2D and 3D settings. These skills will enable them to apply their knowledge towards disease modeling in a dish.
Description of Assignments, Testing and Grading
Evaluation
To be eligible for a passing grade in this class all of the assigned work must be completed.
The factors influencing the final grade and their weights are reported in the following table:
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Class participation |
30% |
|
| Oral Presentations at Journal Clubs | 10% | |
| Documentation of laboratory work/progress | 20% | |
|
Test |
15% | |
| Grant Proposal | Written Project | 20% |
| Oral Presentation | 5% | |
| Total | 100% | |
Class participation covers the following areas:
- Attendance and level of preparation
- Contribution to class discussions, journal clubs and field studies
Class participation is an important part of this course and to receive full credit students should be present at all the scheduled classes and actively participate.
Journal Clubs
Journal clubs are presentations followed by discussions that will be organized throughout the course to analyze certain thematic areas in depth.
Journal clubs are occasions for group work, class discussion, and development of presentation skills; furthermore, they serve as an exercise for critical thinking and reading.
The papers presented during the Journal Club are related to the preceding lesson. The presenting group of the week will have to prepare a presentation. The rest of the class should read the paper as well and prepare one or two questions for the class discussion.
The presentation should have a logical and clear structure and provide relevant information on the background, methods, conclusions, and future perspectives of the presented work. The original data reported in the paper should be presented and discussed in a clear way.
Test
One test will be given during the course, following the theoretical first week of the course. The test will cover the information taught in that section and by guest lecturers. The duration of the test is 120 min.
Grant Proposal
As part of the course you will prepare a Grant Proposal (individually or in small groups). The purpose of the grant proposal is to learn and practice how to design, write, and present a project proposal to receive funding. It aims to develop the students’ ability to think and formulate theoretical hypotheses/experiments and new research initiatives regarding ecological developmental biology. Furthermore, it is an exercise of clear communication targeted at a scientific audience often involved in evaluation committees. Further descriptions will be given during the course.
The grant proposal assignment consists of a written and an oral part. The topic area and a draft of the proposal have to be submitted to the teacher. The final grant proposal consists of a written assignment and a 10 min power point presentation. The aim of the presentation is to develop the students’ ability to give scientific talks and to present their own ideas.
Field Study
This course will be accompanied a field study visiting the stem cell laboratories of either a company or university research group. Field studies are typically a half-day excursion.
Required Readings
- Relevant scientific papers will be send out one month before the start of the course.
Policies
Laptop policy
Use of laptop computers in class is limited and only allowed for taking notes and ad hoc research within the class discussions. Cell phones and other electronic devices should be turned off and stored away. No electronic devices can be taken into the stem cell laboratories.
Academic Regulations
Please make sure to read the Academic Regulations on the DIS website. There you will find regulations on:
DIS - Study Abroad in Scandinavia - www.DISabroad.org
DIS Contacts
Susana Dietrich, Program Director
Jennifer Schulz, Program Assistant, jsc@dis.dk
Science & Health Program Office: Vestergade 7-37
Plan for the course:
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Week 1 |
Theoretical introduction: - Basic embryo development, embryonic stem cells and generation of induced pluripotent stem cells - Discussion and development of of neural and glial differentiation - Students will pick one recent research paper using these models to understand neurodegenerative diseases and will prepare for JC’s in week 3 |
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Week 2 |
Basic training in stem cell culturing: - Generation of induced pluripotent stem cells from fibroblasts (episomal reprogramming) - Maintenance of iPSC – thawing, expansion and freezing - Characterization of iPSC using pluripotency marker immunocytochemistry for validation |
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Week 3 |
Neural and hematopoietic induction: - Application of induction protocols to generate: neurons, astrocytes and microglia - Continuous maintenance of iPSC Student Presentations of JC’s |
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Week 4 |
CRISPR/Cas9 gene editing and brain cell maturation: - Theoretical: Introduction about CRISPR/Cas9 implications for disease modelling and in vivo therapies, including ethical considerations and student group work - Group work: How to design sgRNAs and ssODNs to introduce or repair single nucleotide mutations - Practical: Nucleofection of CRISPR/Cas9 RNP complexes to introduce specific mutations - Practical: Assessment of glial and neural progenitors: ICC and qPCR. Subsequent change to terminal differentiation. |
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Week 5 |
Assessment of mature Brain cells, Organoids and CRISPR gene editing: - Practical: Neurons, Astrocytes and microglia will be provided for assessment; Cerebral organoids will be assessed and compared to 2D methods - Theoretical: Student group work discussion about limitations and advantages using 2D culture systems and organoids |
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Week 6 |
Students will work on finalizing their lab reports as well as their grant proposals which should focus on neurodegenerative diseases and how those can be investigated with the experimental tools presented and performed in the class. Written lab report and 5-page grant proposal needs to be submitted by the end of the week |
Course Summary:
| Date | Details | Due |
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