A 2023 Crick PhD project with James DiFrisco
Project background and description
Our lab is a newly established theoretical biology group. We focus broadly on developing new models and conceptual frameworks for the study of biological complexity, with special attention to the intersection of development and evolution. For students who wish to combine experimental or computational work with the theoretical approaches taken by our lab, co-supervision with another Crick lab is a possibility. Please mention any proposals to that effect in your application.
Our central research themes include:
- Causal complexity of the genotype—phenotype map. The process of biological development from egg to adult can be viewed formally as a mapping from genotype to phenotype. Progress in different branches of genetics has revealed this mapping to be degenerate and very complex, with important consequences for evolution. Current biology deploys multiple conceptual models of the causal role of genes, from single allele substitutions in microevolutionary studies to integrated gene regulatory networks in macroevolutionary comparisons. How can these different models, among others, fit together? How should we understand context-dependency of genetic effects, pleiotropy, and nonlinearity of the GP map and their significance on different evolutionary time scales? [1, 2] This project requires some theoretical background in evo-devo and interest in evolutionary genetics.
- GRN dynamics. An important task of contemporary systems biology is to translate static models of gene regulatory networks to models of dynamics or network behavior. How do dynamical models of gene regulation contribute to our understanding of developmental phenomena such as cell state transitions, cell types, and tissue patterning? What is the evolutionary significance of such models? This project requires some background in the concepts and methods of dynamical systems and could be done in collaboration with an experimental Crick lab.
- Modularity and integration at multiple levels of organization. Gene regulatory networks are often thought to be organized into quasi-discrete “modules.” How does this fit together with non-modular phenomena such as the polygenic basis of quantitative traits? How does genetic modularity relate to the organization of higher-level units, such as cell types, tissue types, and organs? What is the developmental basis for identifying a cell population as a “module”—i.e. a character? [3]. This project requires some theoretical background in evo-devo, quantitative genetics, and/or systems biology.
The exact project will be determined in consultation with the group leader, depending on the student’s background and interests.
Candidate background
I welcome enthusiastic candidates with a background in biology (molecular, cellular, developmental, or evolution), and an interest in conceptual or theoretical issues and approaches in biology. Training in the latter will be provided during the PhD.
If you have any questions about the project, feel free to get in touch with me via james.difrisco@crick.ac.uk
References
1. Pavličev, M. and Wagner, G.P. (2014).
Evolutionary systems biology: Shifting focus to the context-dependency of genetic effects.
In: Integrative Organismal Biology. John Wiley & Sons, Inc. Chapter 6: 91-108. DOI: https://doi.org/10.1002/9781118398814.ch6.
2. DiFrisco, J. and Jaeger, J. (2020)
Genetic causation in complex regulatory systems: An integrative dynamic perspective.
Bioessays 42: 1900226. PubMed abstract
3. DiFrisco, J., Love, A.C. and Wagner, G.P. (2020)
Character identity mechanisms: a conceptual model for comparative-mechanistic biology.
Biology and Philosophy 35: 44.
