CHENE 4870 Synthetic Organogenesis @ Columbia University
Prof. Simunovic created a course that teaches the principles of synthetic approaches in developmental biology. Decades of intense research using animal models revealed an intricate signaling network that drives the specification of the first cell types into all the organ progenitors. Synthetic organogenesis is an emerging field that applies the valuable lessons learned in animal embryos and employs principles from chemical and biological engineering to recreate the signaling pathways that control embryo development and organ formation, with a larger goal of recreating human organs in a lab. It owes its emergence to recent advancements in biotechnology, particularly gene editing, microscopy imaging, and tissue engineering, which have opened up a fresh access to studying the molecular basis of embryogenesis.
The course has three central pedagogical objectives. The first is to introduce students to the basic rules of organ formation, with an emphasis on signaling pathways that lead to cell specification and tissue patterning. At the end of the course, the students will be aware of milestones, and the molecular and signaling mechanisms surrounding the first weeks of human development. The second objective is to expose students to the contemporary literature, specifically to real world demonstrations of how understanding the signaling and morphogenetic mechanisms in the embryo can be mimicked to recreate aspects of organ formation in vitro. In particular, the students will learn synthetic strategies in developing the so-called organoids, stem-cell models of human organs, they will contrast organoids to organ on chip methods, and they will learn about human-animal chimerae and their role in organ manufacturing. The third objective, through in-class discussions, strives at helping students to navigate the barrier between organ engineering and science policy and bioethics.
Lectures from Spring 2020 (changes every year)
Part I On growth and form
Week 1: Similarities and diversities in animal body plans, conservation of molecular pathways. An engineer’s and mathematician’s view of animal body design: Revisiting D’Arcy Thompson’s “On growth and form” -- how do we introduce genetics and signaling molecules into D’Arcy Thompson’s work 101 years later?
Week 2: The first 2 weeks of the human embryo: blastocyst formation, hatching, and implantation. The history of IVF. What we know about cell fate acquisition before organogenesis. What makes implantation so distinct between mice, monkeys, armadillos, horses and humans? Intracellular forces in early embryonic tissues. Student-led paper discussion.
Part II Synthetic approaches in developmental biology
Week 3: What are pluripotent stem cells? Totipotency vs plutipotency vs multipotency. The derivation of human embryonic stem cells as the central tool in synthetic organogenesis. Types of embryonic stem cells: naive, extended, primed, usability and potential crisis in the field. Can we induce pluripotency? STAP scandal discussion. Induced pluripotent stem cells. Embryonic vs adult stem cells.
Week 4: Classical embryology in the contemporary lab. Organ-on-chip vs organoids. Human-animal chimerae as a model to harvest organs. A brief introduction to CRISPR gene editing, imaging, and single-cell sequencing techniques.
Week 5: Can we reconstruct the embryo from stem cells? Blastoids, embryoids, and gastruloids. Trophoblast organoids. The future of the artificial placenta. Student-led paper discussion.
Part III Engineering human organ(oid)s
Weeks 6-7: Retina, the first organoid; From the first brain organoids to detecting waves in mini brains in under 6 years; How close are mini brains to a real brain? Artificial skin. Student-led paper discussion.
Weeks 8-9: In vitro modeling of organs along the gut tube: lungs, liver, intestines, and other organs. Gut on a chip vs gut organoids, which is better? Organoids and Covid research; Student-led paper discussion.
Week 10: Modeling organs derived from mesoderm: cardiac, kidney, urogenital organoids. How close are we to artificial blood? Student-led paper discussion.
Week 11: Final project discussion and defense of project proposals.
Week 12: Global policies on embryo research: Mary Warnock and the 14 day rule. Bioethics of synthetic organogenesis: are embryo models ethical and when they are not? What is organismal potential? The bioethics of brain organoids.