Final Syllabus

Epigenetics and the Environment Spring 2017, Tuesdays and Fridays, 8.30-9.50, V10-A32

Instructor: Kristine Freude, Associate Professor

MSc at Robert Koch Institute and Free University, Berlin, Germany, in 2001 working with Mycobacteria. 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) Pancreas development and human neurodegenerative diseases such as Alzheimer’s and Huntington’s disease. Postdoctoral Researcher (2012-2014) University Copenhagen working with iPSC and stem cell models for neurodegenerative diseases. Assistant Professor (2014-2015) University Copenhagen Stem cell models for neurodegenerative diseases such as Alzheimer’s disease and frontotemporal dementia. Associate Professor (2015-present) University Copenhagen Stem cell models for neurodegenerative diseases such as Alzheimer’s disease and frontotemporal dementia.

My work includes basic research using neurons derived from human induced pluripotent stem cells to develop in vitro disease models and identify novel disease mechanisms as well as overlapping pharmaceutical targets amongst neurodegenerative diseases.

DIS Contacts Lisbeth Borbye, Program Director Susana Dietrich, Assistant Program Director Ryan Polito, Program Assistant Science & Health Program Office, Vestergade 10-B12

Prerequisite: One year of biology and one year of chemistry at university level, including one semester of genetics.

Course Description Epigenetic modifications are one of the main mechanisms underlying the phenomenon by which organisms alter gene expression and phenotypic characteristics in response to environmental conditions. This course will look at how the environment imparts its influence on developmental mechanisms to allow for these phenotypic changes through intersecting developmental biology, ecology, and evolution. Aspects related to symbiosis, teratology and the epigenetic origin of adult diseases will also be addressed.

Learning Objectives  To understand the concepts that integrate phenotypic plasticity, the environment, evolution and development.  To learn the ability to evaluate and criticize experimental evidence in scientific papers.  To be able to incorporate scientific knowledge into a broader framework.  To be able to develop and present a feasible theoretical hypothesis/experiment regarding ecological developmental biology.

Epigenetics and the Environment | DIS 1 Final Syllabus

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:

Class participation 10%

Oral presentations at journal clubs 10%

Test 1 20% Test 2 20%

Test 3 20%

Written project 15% Grant proposal Oral presentation 5%

Class participation covers the following areas: 1. Attendance and level of preparation 2. 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.

Tests Three tests will be given during the course, each following one of the three thematic sections addressed in the course. The tests will cover the information taught in that section during the lessons, presented and discussed at journal clubs, and by guest lecturers. Each test is held in class and takes 60 minutes.

Epigenetics and the Environment | DIS 2 Final Syllabus

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 by 23:00 on March 17. The final grant proposal consists of a written assignment and a 10 min power point presentation. The written assignment is due by 23:00 on December 2. The student presentations take place on December 6 or 9. The aim of the presentation is to develop the students’ ability to give scientific talks and to present their own ideas .

Disability resources Any student who has a need for disability accommodations should contact the office of academic support to coordinate this. Upon DIS approval, students should inform the instructor of accommodations within the first 2 weeks of class.

Academic Honesty DIS expects that students abide by the highest standards of intellectual honesty in all academic work. DIS assumes that all students do their own work and credit all work or thought taken from others. Academic dishonesty will result in a final course grade of “F” and can result in dismissal. The students’ home universities will be notified. DIS reserves the right to request that written student assignments be turned in electronic form for submission to plagiarism detection software. See the Academic Handbook for more information, or ask your instructor if you have questions.

Laptop policy Use of laptop computers in class is not allowed. Cell phones and other electronic devices should be turned off and stored away.

Office Hours The instructors have no set office hours, but you may contact them or the Program Assistant Ryan Polito (Science & Health Program Office Vestergade 10- B12) with any questions or to schedule an appointment.

Attendance You are expected to attend all DIS classes and activities when scheduled, and we will actively monit or attendance. Absences will jeopardize your grade and your standing at DIS. Allowances will be made in cases of illness, but you will need to email your instructor in advance. If you miss multiple classes the Director of Academic Support, and the Director of Student Affairs will be notified and they will follow-up with you to make sure that all is well.

Epigenetics and the Environment | DIS 3 Final Syllabus

Field Studies This course will be accompanied by field studies. The purpose of the field studies is to present active research projects and technologies, to connect course topics to experimental studies, and to serve as inspiration for the grant proposal assignment. Field studies are typically a half-day excursion.

Two field studies will take place during the semester.

Field Study Dates: Wednesday January 25, 13:00-17:00  Biotech Research and Innovation Center “BRIC”. Helin Group Ole Maaløes Vej 5, 2200 København N

Wednesday March 29, 8:30-12:30  Danish Stem Cell Center, University Copenhagen

Guest Lecturer

- Cathy Mitchelmore, Department of Science and Environment, Roskilde University More info: http://forskning.ruc.dk/site/en/persons/cathy-mitchelmore(4eb5bfdc-7338-4ac2-8691- b374312dd365).html

- Philip Seymour, “The Danish Stem Cell Center”, Copenhagen University. More info: http://danstem.ku.dk/people/?pure=en/persons/439072

- Karl Aggar, “BRIC” more info: http://www.bric.ku.dk/staff/Helin_Group/?pure=en/persons/158536

Literature  Gilbert, Scott F., and David Epel. Ecological Developmental Biology: Integrating Epigenetics, Medicine, and Evolution. Sunderland, MA: Sinauer Associates, 2009. Print.  Extra material posted on Canvas

Canvas Canvas is a web-based system that allows you to access course resources and communicate with your classmates and faculty. To access Canvas, you can go to the DIS homepage and click the ‘Canvas’ link on the bottom of the website, or go to: https://canvas.disabroad.org/login/canvas. You can also download the Canvas App (By: Instructure) on iPhone and Android mobile smart phones.

Epigenetics and the Environment | DIS 4 Final Syllabus

COURSE OVERVIEW January

Date Day Lecture # Topic Readings Part I: The environment and normal development

20 Friday 1 Introduction to the course Syllabus Description of the exams, evaluation, reading assignments and the journal club assignments.

Introduction to the basic notions of the course: Chapter 1 of o The environment as an agent in producing Gilbert phenotypes Page 3-32 o What is epigenetics? o What is phenotypic plasticity? 24 Tuesday 2 Environmental Control of Development at the Chapter 2 of Molecular Level: Gilbert o Regulation of gene expression Page o Epigenetic modifications 37-46 o Transgenerational effects 67-72 25 Wednesday

Field Study, 13:00-17:00 Biotech Research and Innovation Center “BRIC”. Helin Group Ole Maaløes Vej 5, 2200 København N

27 Friday 3 Election of class representatives

Journal club group 1 Article #1

Environmental Control of Development at the Chapter 2 of Molecular Level: Gilbert o Neuroendocrine signaling Page o Direct induction 46-66 31 Tuesday 4 Developmental Symbiosis: Chapter 3 of o What is symbiosis and examples Gilbert o Normal mammalian development, symbiosis Page and implications for human health 79-98 February 3 Friday 5 Journal club group 2 Article #2

Developmental Symbiosis: Chapter 3 of o Gut bacteria symbiosis and human health Gilbert Page 98-107 110-114

Core Course Week February 6-10

Epigenetics and the Environment | DIS 5 Final Syllabus

No Class

14 Tuesday 6 Survival and Mechanisms of Embryonic Defense: Chapter 4 o Developmental robustness of Gilbert o Strategies and examples of embryo defense Page factors 119-134

17 Friday 7 Journal club group 3 Article #3

Survival and Mechanisms of Embryonic Defense: Chapter 4 of o Mechanisms of embryo defense Gilbert Page Q&A for the test 134-140 154-158 21 Tuesday 8 Cell differentiation, stem cells and epigenetic Appendix B of patterns Gilbert Page 433-436 24 Friday 9 Test I - Part I A 60-minute test on Part I of the course.

Introduction and description of grant proposals

Q&A

Break / Long Study Tour 1 February 27 – March 3 No Class

March

Part II: Environment, development and disease 7 Tuesday 10 Teratogenesis: Chapter 5 of o What is teratogenesis? Gilbert o Teratogenic agents, examples and effects Page 167-179 10 Friday 11 Journal club group 4 Article #4

Teratogenesis: Chapter 5 o Teratogenic agents, examples and effects 180-186

14 Tuesday 12 Endocrine Disruptors: Chapter 6 of o What are endocrine disruptors? Gilbert o Hormonally active compounds, examples and Page effects 197-212 Journal club group 5

Epigenetics and the Environment | DIS 6 Final Syllabus

17 Friday 13 Journal club group 6 Article #5

Endocrine Disruptors: Chapter 6 of o Hormonally active compounds, examples and Gilbert effects Page o Transgenerational effects 217-218 220-228 Outline of the grant proposal to be emailed to 230-237 teacher by 23.00

Break / Long Study Tour 2 March 20-24 No class

28 Tuesday 14 The Epigenetic Origin of Adult Disease: Chapter 7 of The developmental origin of health and disease: Gilbert o Maternal-fetal co-development and epigenetics Page o Adaptive responses 245-263 o Environment-genotype interactions in diabetes 266-273 o Twin studies 29 Wednesday

Field Study: Wednesday March 29, 8:30-12:30 Danish Stem Cell Center, University Copenhagen

31 Friday 15 Article #6 The Epigenetic Origin of Adult Disease: o Epigenetic mechanisms in cancer Chapter 7 of Gilbert Guest lecturer: Cathy Mitchelmore Page 273-283 April

4 Tuesday 16 Test II - Part II A 60 minute test on Part II of the course

Q&A on grant proposals 7 Friday 17 Q&A on grant proposals Modern Theories of Evolution: Chapter 8 of o Charles Darwin’s Synthesis and natural Gilbert selection Page o Embryology and Darwin’s Synthesis 289-295 o The Modern Synthesis 304-316 Example: Malaria Chapter 9 of Evolution Through Developmental Regulatory Gilbert Genes: Page o Hox genes: duplication and divergence 323-341 o Homologous pathways of development o Developmental modularity

Epigenetics and the Environment | DIS 7 Final Syllabus

11 Tuesday 18 Gene Regulation and Evolution: Experimental Link #1 approaches and Nordic examples Guest Lecturer: Cathy Mitchelmore

Break April 12-17 No Class

18 Tuesday 19 Journal club group 7 Article #7

Evolution Through Developmental Regulatory Chapter 9 of Genes: Gilbert o Mechanisms of macroevolution Page o Speciation 342-352 o Developmental constraints 354-361 21 Friday 20 Environment, Development and Evolution: Chapter 10 of o Epigenetic inheritance systems Gilbert o Genetic assimilation Page o Genetic accommodation 369-395 o Phenotypic accommodation o Niche construction 25 Tuesday 21 Journal club group 8 Article #8

Q&A for the test and grant proposals

28 Friday 22 Test III - Part III A 60 minute test on Part III of the course.

Q&A on grant proposals

Handout of final grant proposals to be emailed to teacher by 23.00

May 2 Tuesday 23 Summary lecture, evaluation of the course Grant proposal oral presentations 5 Friday Reading Day No Class

Oral presentations of grant proposals Wednesday, May 10 Time: 8.30-11.25 Location: V10-A32

Epigenetics and the Environment | DIS 8 Final Syllabus

Article List: Journal club group 1: 1. Weaver et al. (2004) Epigenetic programming by maternal behavior. Nat Neurosci 7(8): 847-54, doi:10.1038/nn1276

Journal club group 2: 2. Spannhoff et al. (2011) Histone deacetylase inhibitor activity in royal jelly might facilitate caste switching in bees. EMBO reports 12:238–243, doi:10.1038/embor.2011.9

Journal club group 3: 3. Vijay-Kumar et al. (2010) Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 9(328): 228-31, doi: 10.1126/science.1179721

Journal club group 4: 4. Fernandes et al. (2015) Embryonic alcohol exposure impairs the dopaminergic system and social behavioral responses in adult zebrafish. Int J Neuropsychopharmacol 18(6): 1-8, doi:10.1093/ijnp/pyu089

Journal club group 5: 5. Dolinoy et al. (2007) Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. Proc Natl Acad Sci U S A 104(32): 13056-61, doi:10.1073/pnas.0703739104

Journal club group 6: 6. Kundakovic et al. (2015) DNA methylation of BDNF as a biomarker of early-life adversity. Proc Natl Acad Sci U S A 112(22): 6807–6813, doi:10.1073/pnas.1408355111

Journal club group 7: 7. Guerreiro et al. (2013) Role of a polymorphism in a Hox/Pax-responsive enhancer in the evolution of the vertebrate spine. Proc Natl Acad Sci U S A 110(26):10682-6, doi:10.1073/pnas.1300592110

Journal club group 8: 8. Rohner et al. (2013) Cryptic variation in morphological evolution: HSP90 as a capacitor for loss of eyes in cavefish. Science 342(6164):1372-5, doi: 10.1126/science.1240276

Links: The evolution of lactose tolerance (15 min film) www.youtube.com/watch?v=MA9boI1qTuk

Epigenetics and the Environment | DIS 9