Dr Saeed Farjami


Research Fellow in Mathematical Biology of Cell Differentiation

About

Publications

Robert N. Kelsh, Karen Camargo Sosa, Saeed Farjami, Vsevolod Makeev, Jonathan H.P. Dawes, Andrea Rocco (2021)Cyclical fate restriction: a new view of neural crest cell fate specification, In: Development148(22)dev176057 The Company of Biologists

Neural crest cells are crucial in development, not least because of their remarkable multipotency. Early findings stimulated two hypotheses for how fate specification and commitment from fully multipotent neural crest cells might occur, progressive fate restriction (PFR) and direct fate restriction, differing in whether partially restricted intermediates were involved. Initially hotly debated, they remain unreconciled, although PFR has become favoured. However, testing of a PFR hypothesis of zebrafish pigment cell development refutes this view. We propose a novel ‘cyclical fate restriction’ hypothesis, based upon a more dynamic view of transcriptional states, reconciling the experimental evidence underpinning the traditional hypotheses.

SAEED FARJAMI, Karen Camargo Sosa, Jonathan H.P. Dawes, Robert N. Kelsh, ANDREA ROCCO (2021)Novel Generic Oscillatory Mechanisms in Models for Differentiating Stem Cells, In: Journal of the Royal Society interface / the Royal Society The Royal Society

Understanding cell fate selection remains a central challenge in developmental biology. We present a class of simple yet biologically-motivated mathematical models for cell differentiation that generically generate oscillations and hence suggest alternatives to the standard framework based on Waddington's epigenetic landscape. The models allow us to suggest two generic dynamical scenarios that describe the differentiation process. In the first scenario gradual variation of a single control parameter is responsible for both entering and exiting the oscillatory regime. In the second scenario two control parameters vary: one responsible for entering, and the other for exiting the oscillatory regime. We analyse the standard repressilator and four variants of it and show the dynamical behaviours associated with each scenario. We present a thorough analysis of the associated bifurcations and argue that gene regulatory networks with these repressilator-like characteristics are promising candidates to describe cell fate selection through an oscillatory process.

Saeed Farjami, Karen Camargo Sosa, Jonathan H.P. Dawes, Robert N. Kelsh, Andrea Rocco (2021)Novel generic models for differentiating stem cells reveal oscillatory mechanisms, In: Journal of the Royal Society, Interface18(183)20210442 The Royal Society

Understanding cell fate selection remains a central challenge in developmental biology. We present a class of simple yet biologically motivated mathematical models for cell differentiation that generically generate oscillations and hence suggest alternatives to the standard framework based on Waddington's epigenetic landscape. The models allow us to suggest two generic dynamical scenarios that describe the differentiation process. In the first scenario, gradual variation of a single control parameter is responsible for both entering and exiting the oscillatory regime. In the second scenario, two control parameters vary: one responsible for entering, and the other for exiting the oscillatory regime. We analyse the standard repressilator and four variants of it and show the dynamical behaviours associated with each scenario. We present a thorough analysis of the associated bifurcations and argue that gene regulatory networks with these repressilator-like characteristics are promising candidates to describe cell fate selection through an oscillatory process.

Additional publications