Investigating the ability of the immune system to promote and permit regeneration

Why some animals have the ability to regenerate complex structures (i.e. limbs), while others cannot, remains an important and open question.

This proposal focuses on how the immune system is able to contribute to the regenerative responses in salamanders which are able to regenerate entire limbs following amputation. This project will be broken down into three aims.

The first aim will investigate the functional requirements for macrophages during limb regeneration developing antibody-free methods to isolate macrophages and knockdown their function to understand their role in regeneration.

The second aim will focus on the adaptive immune system, using CRISPR/Cas9 edited salamanders to investigate whether the adaptive immune system is required for regeneration and determine if adaptive immunity may actually hinder regeneration.

Finally, we will develop a single-cell RNA sequencing-based technology that allows for high throughput and unbiased identification of antibodies that can be used to sort cells of interest.

These projects will combine short-term in vitro work with longer-term in vivo assays that will provide vital information about the role of the immune system in regeneration.

These studies will lay the foundation for an understanding of how the immune system of highly regenerative species is involved with complex multi-tissue regeneration.

This will pave the way for future work that is aimed at how to initiate therapeutic regenerative immunology in patients.