They are not super-corals genetically edited to repopulate the reef. However, the Acropora millepora described in PNAS last week are the first baby polyps ever CRISPRed in a lab, by a team involving Stanford University, UT-Austin and the Australian Institute of Marine Science in Townsville. These uncontroversial organisms pave the way for future experiments to reveal the molecular basis of vulnerability to bleaching, the fatal loss of algal symbionts triggered by global warming. Most corals reproduce once or twice a year, ejecting huge quantities of sex cells resembling underwater snowflakes. The time window of these spawning events can be predicted quite accurately, so researchers can sample the reef at the right moment and collect early embryos for genetic manipulation. We discussed the experiment results and future perspectives of gene editing in corals with the paper’s first author Phil Cleves.
CRISPR knockouts are an effective way to study gene function. Can you please explain how did you choose your target genes?
We chose three genes to focus on for our proof-of-principle experiments that we thought would reveal an obvious phenotype when we knocked them out. Some corals, including Acropora millepora, have naturally occurring fluorescent proteins that make them glow, so these were a convenient choice. We made mutations in the red fluorescent and green fluorescent protein genes expecting to see a clear loss of fluorescence. Although we didn’t observe a dramatic loss of fluorescence as we expected, we were able to make efficient mutations in these target genes. The third gene we chose to modify was FGF1a, which we believe to be involved in coral settlement and metamorphosis. However further experiments are needed to provide additional support for this hypothesis.
CRISPR is a cheap, simple, versatile, multiplexable technique. How is it going to impact your field?
Corals are facing unprecedented declines due to climate change, motivating researchers to understand the molecular basis of their thermal tolerance, how they complete their life cycle, and their interactions with the algae that live inside them (which are expelled when corals “bleach”). Our ability to understand how specific genes contribute to these traits in corals was held back by the lack of methods to test how a particular gene functions in corals. CRISPR has started a genetic engineering revolution by allowing researchers to make precise changes in the genomes to study the role of specific genes in their organism of choice. Myself and co-author Marie Strader knew this technology could have wide-reaching impacts to the field of coral biology. We thought this technology would enable us to test long-standing questions about the basic biology of corals in order to better understand why these organisms are so sensitive to environmental change. It is still too early to tell what the long-term effects are going to be of using CRISPR to study coral biology, but we hope this advancement will allow the community to learn how corals work.
How do you identify the right genes to target in order to crack the genetics of key processes of ecological relevance?
In recent decades, there has been a wealth of genomic and gene expression data generated in corals. This data offers a rich set of hypotheses for what specific genes might be doing in corals. There are so many open questions about which genes help corals thrive in these vibrant and changing ecosystems. The next step for us is to test some of these hypotheses using CRISPR focusing on genes thought to be involved in the symbiosis, bleaching, and skeleton formation. Because there are so many unknowns, it is a very exciting time to do this type of work.
What about CRISPRing the genome of algal symbionts?
In order to have a deep understanding of this symbiotic relationship, we have to understand how genes function in both corals and their algal partners. Therefore, it is critical for researchers to be able to ask what genes do in the algae as well. CRISPR/Cas9 could be an excellent tool for this type of work. Because of this, many groups of scientists are attempting to develop such methods in the algal symbionts.