Lecture Course summary:

The aim of this mini lecture series over 9 days is to explore cell differentiation as a dynamic epigenetic process, contextualized through historical and philosophical perspectives and illustrated with practical examples. This will be designed as a conceptual and pedagogical series of (interactive) lectures – perfect for students interested in questions on cell fate choices made during embryogenesis, growth, development and cellular reprogramming. The topics covered will be:

 Lecture/discussion 1. Origin and history of basic concepts of heredity.

-preformation and epigenesis

-emergence of classical genetics

-concepts of genotype and phenotype

-molecular genetics

 Lecture/discussion 2. Epigenetics: origin and conceptual basis

-how epigenetics is related to genetics and to organicism

-first examples of epigenetic inheritance: parental imprinting

-innate and acquired characters, the debate on the potential role of epigenetics in heredity and evolution

-possible molecular mechanisms

 Lecture/discussion 3. Chromatin as a dynamic structure

-histone modifications and DNA methylation

-how gene expression and chromatin structure are related

-link between energy metabolism and chromatin structure

 Lecture/discussion 4. Cell types, cell differentiation (1)

-single cell studies: the problem of cell classification, cell lineages, differentiation trajectory

-conceptual difficulties: measuring average gene expression?

 Lecture/discussion 5. Cell types, cell differentiation (2)

-epigenetic landscape

-gene networks, complexity

-cell phenotypes as attractors in a multidimensional phenotypic space

-stem cells

 Lecture/discussion 6. Stochasticity in the cell

-conceptual basis, examples

-machine or self-organized dynamic cell?

-noise or driving force

-chromatin structure and stochasticity

 Lecture/discussion 7. Cellular energy-producing processes

-the cell is an out-of-equilibrium thermodynamic system

-energy regime and cell phenotype, a dynamic view

 Lecture/discussion 8. Cell differentiation as a dynamic process

-deterministic or stochastic?

-how order can be system generated by an inherently disordered system?

-Darwinian model of cell differentiation

 Lecture/discussion 9. A non-deterministic dynamic model of cell differentiation integrating the energy constraints, metabolic cooperativity, lineage trajectory and molecular observations.

 10. Conclusion and discussions.

Faculty: Prof. Andras Paldi

Affilication: École Pratique des Hautes Études, Paris

Speaker bio: Andras Paldi is Professor and Director of Studies at the Ecole Pratique de Hautes Etudes – PSL, Paris. Over the years, his group has addressed several fundamental questions in epigenetics and cell fate choices. His early work was on parental imprinting, and later the coordination of differentiation during embryonic development. Recent studies have focused on stochastic variability and fluctuations at a cellular level leading to cell fate choices – with an emphasis on the hematopoetic stem cells. His current research emphasizes the metabolic and epigenetic regulation of cell differentiation in phenotype-genotype-epigenotype relationship.

Course duration: ~9 days (1.5 hour each)

Course dates: 11th Nov – 20th Nov

Lecture time: 2-330 pm daily

Credit: 1 (elective, P/F)