Description: With current advances in technology, the frontier of targeted cell state modulation for medical, research or commercial purposes is getting closer. Yet, efforts to achieve this have been limited and mostly unsuccessful. Few successful examples include the inherited disorders of metabolism, monogenic diseases that have been corrected through curative gene therapy approaches. Yet, our failure to obtain similar successes in most human-relevant conditions which are multifactorial by nature, arises from a precarious fundamental understanding of what a cell state is. In this course, we will explore mathematically based concepts of cell states (mostly as defined by Conrad Waddington), various orthogonal experimental approaches for the modulation of cell states under various contexts and will discuss the advantages and pitfalls of these methods.
Outcome: Ideally, the student will obtain a broader view of the existing experimental strategies to modulate cell states and will come up with an original independent strategy to modulate cell states in a given scenario, providing details on the approach, objective and expected outcomes.
Structure: An introductory discussion on the notion of cells as dynamical systems, followed by student presentations on assigned primary literature covering various approaches for modulation of cell states under various biological contexts and concluding with individual concept papers on approaches to modulate an assigned cell state/biological context.
Grading: Grading will be based on discussion participation, presentation of assigned primary literature, and the concept approach for the modulation of cell states as a final task (1/3 each). Students should read the first 2 chapters of Waddington’s ‘The Strategy of Genes’ and the Perspective paper by Furusawa and Kaneko for the first session. Subsequent sessions until session 7 will involve presentation of assigned papers and participation. Session 8 the concept paper is due.
Course materials: Access to Waddington’s ‘Strategy of the Genes’ and additional literature will be provided as PDFs for students to review in detail.