Frank Chan

Systems Genetics of Evolution

Friedrich Miescher Laboratory
Faculty in: TIPP, IMPRS

Frank has moved to the University of Groningen and no longer recruits students through the IMPRS

Portrait of Frank Chan in his laboratory.

Vita

PhD in the Department of Developmental Biology, Stanford University, 2003-09
Postdoctoral training, Max Planck Institute for Evolutionary Biology, Plön, 2009-12
Max Planck Research Group Leader at the FML since 2012

Research Interest
The genome is in constant evolution. Despite this on-going change, the genome also has to maintain essential functions. Discovering the evolutionary process underlying genome evolution is thus a central goal not only in evolutionary genetics, but also in medicine. Using the house mouse as our model organism, we aim to connect molecular mutations to their phenotypic consequences and track their fate through evolution.
We have pioneered an innovative system to induce mitotic recombination in mouse embryonic stem cells, which allows us to perform genetic mapping for the first time between sister mouse species directly in pluripotent cells. By creating interspecific hybrids between mice with increasing divergence, we can study how traits evolve across species boundaries. Using the in vitro cross system, we can now generate diversity in a single petri dish and directly track how reshuffled genetic combinations may lead to gene expression or cell fate differences between cells. Our in vitro cross approach creates “Impossible Hybrids” – advanced recombinant cell lines that circumvent conventional species barriers.
Our group employs the latest functional genomics and tissue culture techniques, including single-cell sorting and droplet microfluidics techniques to draw out the unique features of every single cell. Our overarching aim is to construct gene networks across evolutionary divergences and connect the dots between individual genetic changes and their evolutionary impacts.
The ultimate goal of our research is to understand how evolution has shaped gene regulatory networks to be tightly, yet flexibly interwoven whole that simultaneously exhibit robustness and a capacity for rapid adaptation.

Two mice of different species and a schematic illustrating in vitro crosses between evolutionarily distant mouse species. — Figure 1. HybridMiX: for the first time we can now directly study the genetic changes between species by performing “in vitro crosses” between evolutionarily distant mouse species. By studying these “impossible hybrid” cell lines using genomics, organ-on-a-chip and organoid techniques we aim to reveal how gene regulatory networks change through six million years of evolution.

Figure 1. HybridMiX: for the first time we can now directly study the genetic changes between species by performing “in vitro crosses” between evolutionarily distant mouse species. By studying these “impossible hybrid” cell lines using genomics, organ-on-a-chip and organoid techniques we aim to reveal how gene regulatory networks change through six million years of evolution.

Fluorescent cell colonies in petri dishes. — Figure 2. Breeding mice in a dish: Using our in vitro recombinant method, we can now generate genetic diversity within a single petri dish. F1 hybrid ES cells carrying a single copy of GFP transgene were grown into colonies. Under control conditions, the whole colony should be uniformly green fluorescent. In contrast, after inducing in vitro recombination, random mitotic recombination gave rise to daughter cells inheriting two or no copies of the GFP transgene, resulting in mixed colonies with variegated GFP expression (right).

Figure 2. Breeding mice in a dish: Using our in vitro recombinant method, we can now generate genetic diversity within a single petri dish. F1 hybrid ES cells carrying a single copy of GFP transgene were grown into colonies. Under control conditions, the whole colony should be uniformly green fluorescent. In contrast, after inducing in vitro recombination, random mitotic recombination gave rise to daughter cells inheriting two or no copies of the GFP transgene, resulting in mixed colonies with variegated GFP expression (right).

Available PhD Projects

Currently not recruiting PhD students.

Selected Reading

Meier, J.I.*, Salazar, P.A.*, Kučka, M.*, Davies, R.W., Dréau, A., Aldás, I., Box-Power, O., Nadeau, N., Bridle, J.R., McMillan, W.O., Rolian, C.P., Jiggins, C.D.†, Chan, Y.F.† Haplotype tagging reveals parallel formation of hybrid races in two butterfly species. (* co-first authors; † co-last authors). In revision at PNAS, also bioRxiv, doi: 10.1101/2020.05.25.113688.
Lazzarano S, Kučka M, Castro JPL, Naumann R, Medina P, et al. (2018) Genetic mapping of species differences via in vitro crosses in mouse embryonic stem cells. PNAS. doi: 10.1073/pnas.1717474115.
Castro JPL, Yancoskie MN, Marchini M, Belohlavy S, Kučka M, et al. (2018) An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice. bioRxiv, doi: 10.1101/378711.