AG Rohner

© Stowers Institute

Feast or Famine: Evolutionary Strategies for Starvation Resistance

How Do Organisms Adapt to Nutrient Scarcity?

Understanding how genotypes, the environment, and developmental processes shape phenotypes is one of the biggest challenges in modern biology. At the AG Rohner, we investigate the genetic, physiological, and cellular mechanisms underlying metabolic adaptation to nutrient-limited environments. Despite the prevalence of food scarcity in nature, the genetic basis of starvation resistance remains largely unexplored. Our lab seeks to fill this gap by studying how certain species thrive despite extreme metabolic challenges.

 

The Cavefish System: A Natural Model for Extreme Metabolic and Immunological Adaptation

Our research leverages the Mexican cavefish (Astyanax mexicanus), a species that has repeatedly evolved in nutrient-poor caves, developing extraordinary physiological adaptations. Unlike their surface-dwelling relatives, cavefish can endure prolonged starvation while maintaining metabolic health, storing excessive fat, and exhibiting glucose homeostasis dysregulation—without the typical negative effects seen in humans, such as metabolic disease or inflammation.

Despite the metabolic adjustments, adaptation to nutrient-poor environment, cavefish evolved an unique immune system. Here, we especially focus on how different environmental factors, such as parasite diversity, affects the evolution of immunity and how other physiological systems, such as metabolism, affect the evolutionary trajectory of the host immune system.

This system allows us to address fundamental evolutionary and physiological questions:

  • What genetic and cellular mechanisms drive starvation resistance?
  • How does metabolism evolve in response to extreme environmental pressures?
  • Can we uncover conserved starvation resistance pathways relevant to human health?
  • How do metabolic adaptations affect the evolution of the immune system?
  • How do pathogen statistics affect the evolution of immunological phenotypes?

 

Our Approach

We use an integrative, multi-scale approach combining:

  • Comparative physiology and metabolism
    • Understanding fat storage, glucose regulation and metabolic shifts in cavefish
  • Genomics, transcriptomics and metabolomics
    • Indentifying molecular pathways responsible for starvation resilience
  • Primary cell cultures
    • Using different flowcytometry assays to study cellular immune phenotypes
  • Custom-developed liver cell lines
    • Providing a powerful in vitro system to dissect starvation responses at the cellular level
  • Functional validation
    • Using CRISPR, transgenesis and metabolic assays to test the roles of candidate genes in starvation adaptation
  • Evolutionary and biomedical perspectives
    • Investigating whether cavefish metabolic traits can offer insights into human metabolic disorders

 

Why Cavefish?

Unlike many non-model organisms, cavefish remain genetically and experimentally tractable. Since cave and surface fish remain interfertile, they provide a rare opportunity to study naturally evolved metabolic traits using powerful genetic tools, including QTL mapping, RNA-seq, and CRISPR-based functional validation.

By exploring the molecular and evolutionary basis of starvation resistance, our work provides insights into extreme metabolic phenotypes that may have biomedical relevance. Why does fat accumulation in cavefish not lead to inflammation, while in humans it contributes to metabolic diseases? Can cavefish teach us new strategies for improving metabolic resilience?

 

Join Us!

We are always looking for motivated students and researchers interested in evolutionary physiology, metabolism, and cellular adaptation. If you are fascinated by how organisms survive under extreme conditions, feel free to contact us!