Big Picture
We take an interdisciplinary approach to study divergent cytoskeletal proteins across phyla.
Cytoskeletal proteins perform many fundamental roles in the cell and are conventionally thought to be conserved throughout eukaryotic evolution. Yet surprisingly, we have found many cytoskeletal genes are rapidly evolving even between closely related species and adapted novel biological functions. We combine evolutionary analyses, cell biology, genetics and biochemistry to understand the causes and consequences of cytoskeletal diversification across phyla.
We have discovered that actin-related proteins (Arps) and tubulins have undergone recent evolutionary diversification in both Drosophila and mammals via gene duplications and accelerated amino-acid substitutions (positive selection). While most Arps and tubulins are ubiquitously expressed, this recent genetic innovation in Drosophila and mammals is testis-enriched in expression. Despite the recurrence of novel Arps and tubulins across species, we have little understanding of what roles these cytoskeletal proteins perform. Our recent findings indicate that divergent Arps and tubulins have specialized for tissue-specific roles and may have even acquired critical functions beyond the male germline.
Our current research focuses on the roles of divergent Arps and tubulins in both flies and humans, and we are also studying the impact of their misexpression in cancer. We regularly leverage evolutionary analyses to uncover additional cytoskeletal genes that are rapidly evolving to understand why they are under selective pressure to diversify in sequence and function.
Current Questions
What are the germline functions of divergent Arps in Drosophila?
We have found that several divergent Arps in Drosophila localize to germline-specific actin structures. What are the molecular roles of Arps at these germline structures, and how do they impact fertility?
What roles do divergent Drosophila Arps play beyond the testis?
The most functional work on divergent Arps has been done on a non-canonical Arp in Drosophila: Arp53D. Despite having highest expression in the testis, Arp53D impacts female fertility and heat-stressed embryogenesis. Females lacking the Arp53D gene lay embryos with reduced nuclear integrity and lower viability. How does Arp53D impact embryonic development, and does it play a role in the heat stress response? Do additional ‘testis’ Arps also play roles in development?
What are the germline functions of divergent cytoskeletal proteins in mammals?
Mammals encode divergent Arps and tubulins that are predominantly expressed in the testis, yet their functions are completely unknown. Do mammalian ‘testis’ cytoskeletal proteins also localize to the cytoskeleton and play roles in and beyond the male germline similar to Drosophila Arps?
How do divergent cytoskeletal proteins in flies and mammals impact cytoskeletal biochemistry?
Since the ability to polymerize underpins many of actin and microtubule functions, we are testing the polymerizing capability of divergent ‘testis’ cytoskeletal proteins and investigating their interactions with canonical actin and tubulin to determine how structural divergence impacts cytoskeletal dynamics.
How do abnormally expressed testis cytoskeletal proteins promote cancer cell survival in humans?
Reproductive proteins are often misexpressed in many cancer types and can confer a selective advantage in the tumor cell. A subset of these misexpressed proteins are divergent cytoskeletal proteins that are normally restricted to the testis. We are studying how these proteins may equip cancer cells with a survival advantage.
