FUNDED PROJECTS

The Catalyst Science Fund has grown from one project in 2018 to eight in 2019. More projects will be launched in the coming months. Our six areas of focus include Genomic Insight, Synthetic Alternatives, Restoring Diversity, Facilitated Adaptation, and De-extinction. While most projects are focused on a single species, the purpose of each projects is to catalyze biotechnology developments that will be useful across species and applications.

Restoring Genetic Diversity

Interspecific Cloning of the Black-Footed Ferret (BFF)


Led By: Viagen Pets

Status: Active (May 2019–September 2020)

Goal: Demonstrate the potential for interspecific cloning of BFFs using domestic ferret surrogates.

Why Now: All living BFF trace their genetics to just 7 ancestors. Due to this, the current BFF population possesses just 85% of its original genetic diversity. Genetic drift will cause this diversity loss to continue. However, cryopreserved BFF cell lines at the San Diego Global Zoo’s Frozen Zoo possess genotypes that could greatly improve BFF biodiversity—if these genotypes can be cloned and bred into the current population. Learn more about the Black-footed Ferret.

Catalytic Science: Because every surviving BFF is vital to the recovery program, it is necessary to rely on domestic ferrets to act as surrogates in cloning the BFF. This project will determine if the interspecific cloning approach is a possibility for introducing new genetic variation into the breeding BFF community.

Canine Distemper Virus (CDV) Removal from BFF Cell Culture


Led By: ImQuest BioSciences

Status: Active (July–December 2019)

Goal: Remove CDV particles completely from an infected BFF cell line, making those cells suitable genetic donors in subsequent cloning experiments.

Why Now: The Frozen Zoo at San Diego Zoo Global currently holds two cryopreserved cell lines from two BFFs—one male (SB2) and one female (SB10). Cloning these genomes and integrating them into the captive breeding program would effectively introduce two new founders into the living BFF population and boost their genetic diversity. Learn more about the Black-footed Ferret.

Catalytic Science: During the process of obtaining genomic sequences of SB2 and SB10, researchers at the Frozen Zoo discovered that the SB2 cell line is contaminated with an active infection of canine distemper virus (CDV). Therefore, SB2 is not currently able to serve as a source of donor nuclei for cloning experiments.

For these cells to be used in a cloning experiment, it is necessary that all CDV particles be removed from the SB2 cell line. This methodology will also need to preserve cell viability and genetic integrity, and render the cells suitable for cloning.

Inherited Vectored Immunoprophylaxis for Sylvatic Plague in a Mouse Model


Partners: Texas A&M Institute for Genomic Medicine and United States Geological Survey (USGS) National Wildlife Health Center

Status: Active (July 2019–October 2020)

Goal: Demonstrate the potential to create heritable immunity to plague in the Black-footed ferret (BFF)

Why Now: Sylvatic plague caused by Yersinia pestis bacterium kills the BFF at nearly a 100% mortality rate. It is the largest obstacle to the self-sustaining recovery of this endangered prairie native. Learn more about the Black-footed Ferret.

Catalytic Science: This project will provide proof-of-concept for an approach to engineer gene-mediated plague resistance in the BFF. To quickly evaluate the efficacy of this approach, a mouse model will be used over multiple generations.

De-extinction

Developing Primordial Germ Cell Techniques for Germline Transfer


Led By: Dr. Rosemary Walzem, Texas A&M University

Status: Active (July 2019–June 2021)

Goal: Identify key points in Primordial Germ Cell (PGC) biology to govern the success of PGC culture and transfer between wild and domestic bird species. 

Why Now: A critical step in avian genetic rescue will be the ability to isolate, culture, and expand avian PGCs (the cells that give rise to spermatozoa and oocyte cells) in vitro—a step that has not yet been accomplished for wild bird species. Learn more about the genetic rescue of the heath hen and the passenger pigeon.

Catalytic Science: Fundamentally, reproductive technologies available for genetic rescue in mammals do not work for birds. Egg-based reproduction presents a unique set of technical challenges. The success of this project will help enable genetic rescue projects for many avian species. In October, a flock of young greater prairie chickens from our breeder, Dan Snyder, arrived in Texas. New experiments to culture PGCs will begin when these birds lay eggs in 2020. Findings will be applied to support heath hen de-extinction efforts and genetic rescue of its living relatives, including the critically endangered Attwater’s prairie chicken.

 

Facilitated adaptation

Assembling the EEHV1A Genome to Save the Endangered Asian Elephant from Disease


Led By: Dr. George Church, Harvard Medical School 

Status: Active (July 2019–June 2020)

Goal: Create a cell culture system for Elephant Endotheliotropic Herpes Virus 1A (EEHV1A) using a synthesized viral genome.

Why Now: Captive breeding efforts of the endangered Asian elephant (Elephas maximus) are currently hindered by the elephant endotheliotropic herpesviruses (EEHV), a widespread and highly fatal hemorrhagic disease that results in a 25% mortality rate for captive-born Asian elephant calves. Developing new strategies to fight this disease is essential for Asian elephant conservation. Unfortunately, all previous attempts to propagate the virus in cell culture models have failed. Without the ability to culture the virus in the laboratory, it is difficult to identify its’ mechanism of action, understand  its host-virus interactions, develop vaccines, or screen new antiviral drugs.

Catalytic Science: The Church lab has proposed taking two parallel approaches to assembling the complete EEHV1A genome from synthetic DNA fragments and transfecting it into Asian elephant endothelial cells to create a cell culture platform. Once this has been achieved, they plan to use electron microscopy to test whether viral particles are being made. Learn more about work from the Church Lab.

Invasive species control

Novel method for in vivo gene editing of vertebrate embryos


Led By: Dr. Alison Van Eenennaam, University of California Davis

Status: Active (June 1, 2019–May 31, 2020)

Goal: Proof-of-concept for a novel method of in vivo gene editing to deliver gene-editing machinery into developing oocytes.

Why Now: There are many issues with current gene editing methods that preclude their use for conservation purposes. These include the inaccessibility of oocytes or embryos for microinjection, the inefficiency of microinjection and embryo transfer, and the unique culturing conditions required for oocytes and embryos of a variety of species. The Van Eenennaam lab has designed a novel method of gene editing that eliminates all of these steps by modifying early embryos in vivo.

Catalytic Science: This is a proof-of-concept effort to test a novel gene editing method based on cellular therapeutic technologies.

Genomic Insight

Coral Stress Triggers as Targets for Genetic Intervention and Climate Change Resilience


Led By: Dr. Steve Palumbi, Stanford University

Status: Completed (January to October 2019)

Goal: Establish a new research paradigm using pharmacological agents to explore the cellular controls that trigger coral bleaching.

Why Now: Coral death is precipitated by bleaching events—so-called because the coral’s symbiotic dinoflagellates (algae) exit the coral—which leave it white. Learn more about coral threats in our Ocean Genomics Horizon Scan. Recent studies show a set of cellular switches may be involved in triggering coral bleaching, the most promising of which is the unfolded protein response (UPR). While UPR is correlated with bleaching, it isn’t known whether UPR triggers bleaching. This project tested the possibility that UPR is a fundamental part of the coral bleaching trigger.

Catalytic Science: The typical way to test such a hypothesis is through genetic manipulation of cultured cells—yet traditional genetics techniques are not feasible in corals. Without the ability to manipulate coral genomes directly, coral geneticists cannot directly test their hypotheses. To make immediate progress in coral genetics, a novel strategy was borrowed from studies in cancer and cell biology. The Palumbi laboratory used pharmacological agents, that have specific effects on highly conserved proteins, to study coral cell biochemistry.

Results & Next Steps: The pharmacological agents were successful in manipulating coral gene expression, showing their utility for corals research. To inform strategies for intervening in the coral reefs’ destruction, high-throughput approaches to scale-up, and speed-up this approach to coral genetics research should be explored.