Tim Cherry, PhD
Assistant Professor, Seattle Children’s Hospital Research Institute, Center for Developmental Biology and Regenerative Medicine
Dan Doherty, MD, PhD
Professor of Pediatrics, Divisions of Developmental Medicine and Genetic Medicine, University of Washington and Seattle Children's Hospital
Genetics Core Director, University of Washington Center on Human Development and Disability
Co-Director, Developmental Neuropsychiatry Program, Seattle Children's Hospital
Jay Sarthy, MD, PhD
Attending Physician, Pediatric Bone Marrow Transplantation, Seattle Children's Hospital
Acting Instructor, Department of Pediatrics, University of Washington School of Medicine
Oct. 1 - Dec. 5
Note: The Sept. 26th class is canceled due to overlap with the Human Biology Division Retreat.
Tuesdays and Thursdays
3:20 - 4:40 PM
Room B1-074/076 (next to Pelton Auditorium), Weintraub Building, Fred Hutch Campus
60% Class participation including round-table discussions and primer presentations
40% Final paper (see Assignments tab)
The Annual Winter Developmental Biology Symposium will be held on Friday December 6th, 2019 from 1:00 PM - 6:00 PM. This year's guest speakers will be Siobhan Braybrook (UCLA; Siobhan takes a systems-level approach to understanding the development of tissue and organ shape in plants) and Tim Cherry (Seattle Children's Hospital Research Institute; Tim studies how mutations in regulatory sequences can cause human developmental disorders of the eye). Please plan to attend!
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.
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.
View this extraordinary 1965 movie, "Overture" by Janos Vadosz in which chick development is set to Beethoven's Egmont Overture:
This video is of a comparable period during the development of a zebrafish embryo:
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:
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.
Oct. 8: Lecture: limbs, cilia, sonic hedgehog and Lil’ Bub
Oct. 10: Literature review
Oct. 22: Lecture: Kartagener’s syndrome, left-right patterning and more cilia
Oct. 24: Literature review
Oct. 29: Alagille syndrome and spondylocostal dysostosis: defects in mesodermal segmentation
Oct. 31: Literature review
Note: Class on October 31st will be from 1:20-2:40 PM
Nov. 5: Guest Lecturer: Tim Cherry, Phd: Regulatory Mutations and Human Genetic Disease
Nov. 7: Literature review
Nov. 12: Ectodermal Dysplasia, hair, scales, feathers and teeth
Nov. 14: Literature review
Dec. 3: Lissencephaly and Microcephaly – Defects in Neuron Migration and Neurogenesis
Dec. 5: Literature review