The JGI was honored to host some of the brightest minds in genetics as part of our 2022 Annual Meeting. The meeting was a hybrid event, with guests joining onsite at the Integrative Genomics Building at Lawrence Berkeley National Laboratory (Berkeley Lab) as well from across the globe via their laptops or even smartphones.
This year’s three-day conference featured keynote speeches from Nobel Laureate Jennifer Doudna of the University of California, Berkeley and Berkeley Lab, who discussed the exciting progress in gene editing made possible by CRISPR-Cas9; the Weizmann Institute of Science’s Assaf Vardi, who delved into algae blooms and the alga-viral interactions within them; and Susan Wessler of UC Riverside, who discussed her work on transposable elements and how understanding these genes has helped pave the way for the conception of a pangenome.
Jennifer Doudna, UC Berkeley
“We soon realized that we had a powerful tool.”
Keynote Talk Title: CRISPRology — The Science and Applications of Genome Editing (Virtual)
Jennifer Doudna is a professor at UC Berkeley and a faculty scientist with Berkeley Lab, among other affiliations.
In Doudna’s keynote presentation, she took the audience down memory lane, recounting the earliest days of discovering CRISPR-Cas9, the powerful gene editing technology that resulted in her 2020 Nobel Prize in Chemistry. She then pivoted towards the future and shared ways that her team is looking to use CRISPR-Cas9 to solve new problems.
According to Doudna, the CRISPR-Cas9 investigations began as “curiosity driven research.” In the early 2000s, UC Berkeley colleague and longtime JGI collaborator Jill Banfield approached Doudna with repeated genetic sequences (already known as CRISPR) that came up in her team’s metagenomic samples. While Banfield continued exploring the interactions between the bacteria and viruses in their samples, Doudna and her team investigated the enzymatic mechanisms behind CRISPR.
“We soon realized that we had a powerful tool,” Doudna said during her keynote. In 2012, Doudna published results indicating how CRISPR Cas-9 could be used as a DNA cleaver and gene editing technology. In her keynote presentation, Doudna walked the audience through the detailed steps taken during their experimental journey to this discovery.
Now, Doudna and her team are building on this discovery to address a wide range of new questions — from basic research, like learning how to optimize the gene editing function of CRISPR-Cas9, to more advanced therapeutic applications like overcoming antibiotic resistance and discovering new ways to combat disease.
In speaking more specifically to the JGI Annual Meeting audience, Doudna also discussed her interest in how this technology could be applied to curbing methane emissions of livestock. Currently, adjusting the diet of animals can help to lower greenhouse gas emissions, however, it’s too costly to realistically implement. CRISPR-Cas9, Doudna said, may work better and be more cost-effective.
“There are still a lot of unlocked questions to answer,” she said.
Assaf Vardi, Weizmann Institute of Science
One cell can change large-scale processes
Keynote Talk Title: Host-virus dynamics in the ocean (Virtual)
“Although single-celled, photosynthetic organisms can form massive blooms in the ocean that can stretch over thousands of square kilometers, and that’s hugely important – serving as half of the photosynthetic activity on Earth,” Weizmann explained.
These algae take up carbon dioxide and emit oxygen and other gasses — some of those gasses create “the smell of the sea, that you all know,” Vardi shared. Crucial for the global carbon cycle, photosynthetic phytoplankton do not operate alone. Viruses infect them, and that can have a great impact on these algal blooms.
So Vardi and his group study one specific alga, Emiliania huxleyi (sequenced by the JGI), and the virus that infects it, Emiliania huxleyi virus, to see what those infection dynamics mean for these vast algal blooms. Their work takes a view across many scales: from natural blooms in the ocean, down to smaller, induced algal blooms, plaques from the algae that form these blooms, all the way to individual cells, and the metabolites, vesicles, and virions they produce.
To understand these algae-virus interactions at smaller and smaller scales, his lab has developed an ever-growing suite of approaches, many of which profile both algal cells and infecting viruses simultaneously. With a better understanding of the metabolomic and transcriptomic implications of these viral infections — at single cell resolution — Vardi and his group are getting a better idea of how these tiny interactions shape carbon cycling in the ocean.
“So very interesting to think, how the fate of a single cell in the ocean can really change large-scale processes.”
Susan Wessler, UC Riverside
Shaping up conservative genomes
Keynote Talk Title: Transposable Element-Mediated Structural Variation — From McClintock to Pangenomes
Susan Wessler is plant molecular biologist and geneticist and currently a distinguished professor of genetics at UC Riverside. Her work focuses on identifying transposable elements (TEs) — also known as “jumping genes” because these genes can change position within a genome — in plants to see how they impact gene and genome evolution. TEs are the largest component of a genome sequence, accounting for 45% of the human genome and 50-80% of certain plant genomes including maize, wheat and barley.
During her keynote speech to JGI staff and users at our 2022 Annual Meeting, Wessler discussed the revolutionary work of Barbara McClintock, who discovered transposition and its ability to turn character traits on and off and, “who I had the great fortune to know at the beginning of my career, with my postdoctoral project beginning with her strains,” Wessler explained.
“She was a master of the technology of cytogenetics, which was really the way that people looked at genomes way back then, and she was the best in the world.”
McClintock brought this background, which focuses on cell biology and how the structure and function of chromosomes relate to inherited traits, and applied it to groundbreaking genetics. This work paved the way to move beyond a single case-study, the reference genome, to something that represents all of the genes within a species.
A pangenome, then, consists of those sequences shared among all individuals in a given species as well as what’s called the “dispensable” genome — those little individual variabilities within a species that hold clues for maximizing the genetic code’s potential. And those clues hinge on TEs: Where are they, what are they doing, and what traits are expressed based on their movement?
Through the recombination process, Wessler is among a slew of scientists who have built their careers off McClintock’s early work by identifying mutations that, for example, turn maize (where McClintock originally discovered TEs) into corn starch.
“There are lots and lots of agronomically important mutations,” Wessler said during the JGI Annual Meeting.
Wessler’s work remains keenly focused on understanding how genome evolution is impacted by TE activity. Her lab has leveraged bioinformatics in computational analysis to identify and characterize TEs, developing software to annotate them in plants other than maize including black cottonwood, rice, Arabidopsis, Mimulus and Amborella (in preparation).
“Transposable elements shape up otherwise conservative genomes in ways that we are just beginning to understand,” Wessler said, in closing.
More information about Susan Wessler’s work is available on the Wessler Lab’s website.