Our Research

We decode the regulatory wiring of the genome to understand the genetic basis of complex phenotypes such as diapause and aging using killifish as the model system

Our Model

We use multiple species of killifish as our model system. Some of these species, such as the African turquoise killifish are vertebrate extremophiles. They can survive in ephemeral ponds that dry up completely for up to 8 months each year. To survive in this harsh habitat, they have evolved two remarkable adaptations:

1) A form analogous to ‘suspended animation’ called diapause. Diapause helps embryos survive the annual drought. Diapause embryos already have complex developing organs and tissues and can live for years (5 times longer than their adult lifespan) with no discernible tradeoff for future life.

2) A compressed adult life with rapid sexual maturation and the shortest vertebrate lifespan in captivity (~6 months). In their short lives, they show several signs of human aging and diseases including neuro-degeneration, and cognitive decline.

These two phenotypes make them a rapid vertebrate model to study diapause, aging and age-related diseases.

There are over 1200 killifish species worldwide. These sturdy fish can survive in a range of habitats and have a rich diversity of phenotypes. Notably, species that live in ephemeral ponds in Africa and South America can undergo diapause of varying lengths and have shorter lifespans. Their closely related killifish that live in permanent water bodies like big rivers and lakes cannot undergo diapause and are significantly longer-lived. These killifishes thrive in the same lab environment and exhibit large lifespan difference. This natural diversity provides a unique opportunity to identify determinants of vertebrate lifespan plasticity by leveraging nature's long-term evolutionary experiments.


We use interdisciplinary approaches with a combination of single-cell and bulk 'omics' technologies, CRISPR-based perturbations, and computational modeling to decode the gene regulatory networks during diapause, aging, and evolution.
There are often no off-the-shelf methods for many aspects of our work. We also develop new computational and experimental approaches to fill those gaps.

Current Research

Genomic basis of the protective mechanisms in diapause

Embryonic diapause in killifish is analogous to a state of 'suspended animation' which can protect complex embryos from damage and aging without detectable future tradeoffs. We are interested in dissecting the gene regulatory network underlying these protective mechanisms, and how these novel regulatory elements (e.g. enhancers and promoters) have evolved.

Genetic regulation of metabolic remodeling in diapause

The state of diapause is associated with a drastic remodeling of the metabolic profiles of multiple cell types and tissues. This metabolic remodeling is critical for their long-term survival. We are interested in identifying the precise nature of metabolic changes that occur in diapause embryos, how they are regulated, and how they differ from the embryos of other species that cannot undergo diapause.

Regulation of longevity differences across species

Leveraging the tractability and remarkable natural diversity of lifespans and other relevant phenotypes across different killifish species, we aim to understand the regulation of the rate of aging and the evolution of longevity across species.

© Singh lab UCSF, 2023