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
Aakanksha Singhvi, PhD
Assistant Professor, Basic Sciences, Fred Hutch
asinghvi@fredhutch.org
Tim Cherry, PhD
Assistant Professor, Seattle Children’s Hospital Research Institute, Center for Developmental Biology and Regenerative Medicine
Timothy.Cherry@seattlechildrens.org
Jeff Rasmussen, PhD
Assistant Professor, Department of Biology, University of Washington
rasmuss@uw.edu
Jan. 4 - Mar. 7
Tuesdays and Thursdays
3:30 - 4:50 PM
In person (no hybrid option).
70% Class participation including round-table discussions and primer presentations
30% Final paper (see Assignments tab)
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.
The genes that are implicated in human disease, from dysmorphologies to neurodevelopmental disorders to cancer predisposition, are frequently well known to developmental biologists. Decades of genetic screening in model organisms for ostensibly unrelated phenotypes—for example the hairs on a fly wing or the scales on a fish—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 genes that have been identified based on human disease phenotypes informs developmental biologists of unanticipated genetic connections and suggests hypotheses about the genetic control of development that can be tested in model organisms.
LEARNING GOALS
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 questions in developmental biology.
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
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.
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.
Jan. 4: Introduction to embryo development and human genetics
Jan. 9: Guest Lecture: Jay Shendure: Mammalian development at the level of the single cell.
Jan. 11: Literature Review
Jan. 16: Lecture: Limbs and Digits: from Holt Oram Syndrome to Lil Bub.
Jan. 18: Literature review
Jan. 23: Guest lecturer Tim Cherry: non-coding causes of human genetic disease
Jan. 25: Literature review
Jan. 30: Lecture: Left-Right Asymmetry: From Kartagener’s Syndrome to Kuppfer's Vesicle.
Feb. 1: Literature review
Feb. 6: Guest lecturer Stephen Tapscott: Cancer as a gain-of-function disorder of development
Feb. 8: Literature review
Feb. 13: Lecture: Segmentation: From Alagile Syndrome to the Ohio State Football Stadium
Feb. 13: Literature review
Feb. 20: Guest lecturer Aakanksha Singhvi
Feb. 22: Literature review
Feb. 27: Lecture: Brain development: From the Turkish hand-walkers to the centrosome.
Feb. 29: Literature Review
March 5: Guest lecturer Jeff Rasmussen: Ectodermal Appendages: From Feathers to Fingerprints
March 7: Literature review