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MCB 522 Developmental Basis of Human Disease: Course Info

MCB 522 Faculty

Course Instructor:

Cecilia Moens, PhD
Member, Division of Basic Science, Fred Hutch
Affiliate Professor, UW Biology
cmoens@fredhutch.org


Guest Lecturers:

Jay Shendure, PhD
Professor, Genome Sciences, University of Washington
shendure@uw.edu

Stephen Tapscott, MD, PhD
Member, Human Biology Division, Fred Hutch
stapscot@fredhutch.org

Tim Cherry, PhD
Assistant Professor, Seattle Children’s Hospital Research Institute, Center for Developmental Biology and Regenerative Medicine
Timothy.Cherry@seattlechildrens.org

Time & Location

Sep. 29 - Dec. 10

Tuesdays and Thursdays

3:30 - 4:50 PM

We will start out fully virtual however may move to hybrid if allowable and if there is interest.

Join Zoom Meeting https://us02web.zoom.us/j/81594003357?pwd=a2hhMmpNdi9va2toWnRxdjFjb05wdz09
Meeting ID: 815 9400 3357
Passcode: 367201

Grading

60% Class participation including round-table discussions and primer presentations
40% Final paper (see Assignments tab)

CANCELED: Developmental Biology Symposium

The Annual Winter Developmental Biology Symposium will be held on Friday December 3rd, 2021 from 12:00 PM (noon) - 5:00 PM followed by a Happy Hour and Poster Session. All pending lower COVID levels in the community of course. Please plan to attend!

Course Overview & Learning Goals

This course is intended to introduce graduate students to concepts in developmental biology that are made particularly relevant by their implication in human genetic disorders and cancer.

As human geneticists use new sequencing technologies to discover the mutations underlying human genetic diseases – from autism to rare dysmorphologies to cancer predisposition – they are frequently identifying genes that are already familiar to developmental biologists. Decades of genetic screening in model organisms for ostensibly unrelated developmental phenotypes – the orientation of hairs on a fly wing or the formation of the worm vulva – has identified genes and pathways controlling virtually every aspect of animal development. The developmental biology literature is a rich resource for clinicians who seek to understand the underpinnings of their patient’s disorders, to identify candidate interacting genes and in some cases, to discover therapies. Conversely, the burgeoning number of genes that are being identified based on human disease phenotypes is informing developmental biologists of unanticipated genetic connections and suggesting hypotheses about the genetic control of development that can be tested in model organisms. A particular focus of the course in will be on the developmental basis of cancer: how changes in the sequence or expression of developmental control genes can lead to cancer; how developmental pathways are co-opted in cancer cells and the cancer microenvironment; and the relationship between the cancer cell phenotype and the normal developmental processes of growth and differentiation.

LEARNING GOALS

This ten-week course will explore the intimate relationship between human genetic disease and developmental biology. Each week we will choose a different human disorder whose genetic basis has been discovered, and we will discuss how the same genes regulate key processes in animal development. The second meeting of each week will be an opportunity for students to discuss recent papers from the literature relating to these developmental processes. We will end each week by formulating hypotheses about how mutations in these developmental control genes may cause the human disease in which they have been implicated. While a comprehensive understanding of developmental biology is far beyond the scope of this course, a goal is for students to complete the course with an understanding of 1) the major developmental signaling pathways; 2) how changes in signaling through these pathways can cause human disease, and 3) an appreciation of the current approaches that are being taken to answer outstanding questions in developmental biology.

Video

View this extraordinary 1965 movie, "Overture" by Janos Vadosz in which chick development is set to Beethoven's Egmont Overture:

http://www.daazo.com/film/5698ae82-910e-102c-a455-000e2e531ae0

This video is of a comparable period during the development of a zebrafish embryo:

https://www.youtube.com/watch?v=EeHiA98yUa4

Early mouse gastrulation from light-sheet imaging of in vitro cultured embryos, showing the origins of the major germ layers and some of their derivatives:

https://www.youtube.com/watch?v=5Q9wFeaGGYs

Cell lineage reconstruction of a zebrafish embryo during the first 12 hours of development

https://www.youtube.com/watch?v=luttZD-rpE0

Reference Books & URLs

This book was the inspiration for me to teach this course. The science is now out of date but read it for the empathetic historical retelling of how different classes developmental disorders were described and how the people who suffered with them were treated in times before the underlying biology was uncovered.


Lectures

Classes will alternate between lectures and round-table discussions of papers from the current literature. All students should read the papers being discussed before coming to class, as everyone will be involved in presenting and discussing them. Class reading assignments and pdfs of slides for the lectures will be available from the E-reserves page (blue tab above). Reading assignments will generally be posted one week or more in advance. Lecture notes will be available by noon of the day of the lecture.

Week 1

Sept. 30: Introductory Lecture: Mendelian Disorders Reflect Principles of Developmental Biology

Week 2

Oct. 5: Guest Lecture: Jay Shendure: Single-Cell Insights into Developmental Biology

Oct. 7: Literature Review

Week 3

Oct. 12: Guest Lecture: Stephen Tapscott: Cancer as a Developmental Disorder

Oct. 14: Literature Review

Week 4

Oct. 19: Lecture: Limbs and Digits: from Holt-Oram Syndrome to Lil Bub

Oct. 21: Literature Review

Week 5

Oct. 26: Guest Lecture: Tim Cherry: Regulatory Mutations and Human Genetic Disease

Oct. 28: Literature Review

Week 6

Nov. 2: Lecture: Left-Right Asymmetry: from Kartagener’s Syndrome to the F-molecule

Nov. 4: Literature Review

Week 7

Nov. 9: Lecture: The Brain: From Lissencephaly to Huntington’s Disease

Nov. 11: Literature Review

Week 8

Nov. 16: Lecture: Segmentation: From Alagille Syndrome to the Ohio State Football Stadium

Nov. 18: Literature Review

Week 9 (Thanksgiving Week)

Nov. 21: Catch-up reading from Veteran’s day

Nov. 23: Student Cancer Presentations

Week 10

Nov. 30: Lecture: Ectodermal Appendages: From Feathers to Fingerprints

Dec. 2: Literature Review

Week 11

Dec. 7: Lecture: Student Choice

Dec. 9: Final Literature Review: Dinner Party Format