Overview
How predictable is evolution? This fully funded PhD explores one of biology’s most enduring questions: when species face the same challenge, do they reliably evolve the same molecular solution, or do deeper constraints steer evolution along different paths [1]?
About this opportunity
You will investigate this question using a powerful natural experiment: the evolution of resistance to cardiotonic steroids (CTSs), potent toxins produced by plants, insects, and amphibians. These compounds disable Na,K-ATPase, a key ion pump for nerve and muscle function [2]. For most animals, CTS exposure is fatal, yet across the tree of life many species have independently evolved resistance through changes at just a handful of amino acids [3,4].
Our recent research shows that this convergent evolution is far from guaranteed: the same substitution can be beneficial in one lineage and harmful in another [5]. These contrasting outcomes reveal the decisive roles of protein structure, epistasis, and evolutionary history in shaping which adaptive solutions are possible, and which are blocked [6].
Birds provide an exceptional system for testing these ideas. Some species can consume toxic insects or amphibians that would kill most vertebrates. With diverse ecologies and repeated exposures to CTS-bearing prey, they offer natural replicates of selection [7].
Beyond evolutionary theory, this work will contribute to broader efforts in predicting evolutionary responses to environmental change, understanding protein-level constraints relevant to biotechnology, and building generalisable rules of molecular adaptation.
What You Will Do
This multidisciplinary project combines comparative genetics, protein engineering, structural biology, and functional biochemistry to address three key questions:
1. Where has convergence occurred, and where has it not?
Identify convergent, lineage-specific, and novel substitutions across avian Na,K-ATPase using genomic resources and targeted sequencing.
2. What do these substitutions actually do?
Use ancestral protein resurrection, expression, and biochemical assays to quantify their effects on CTS resistance, ATPase activity, and evolutionary trade-offs.
3. How does evolutionary history shape adaptive accessibility?
Replay substitutions across reconstructed ancestral ATP1A proteins to reveal how prior mutations and structural context constrain or enable adaptation.
Along the way, you will generate unique datasets and resurrect long-extinct protein variants to directly test evolutionary hypotheses.
Impact
This project will reveal when and why molecular convergence succeeds or fails, advancing our ability to predict evolutionary outcomes and uncovering the structural limits of protein adaptation. Your findings will deepen our mechanistic understanding of how life repeatedly, and sometimes unexpectedly, solves extreme biochemical challenges.
Come join us in discovering the rules that shape the evolution of life’s most remarkable adaptations.