Erich Schwarz: in the beginning was the worm (C. elegans)
Feb 3, 2024
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Geneticist Erich Schwarz discusses the significance of studying worms in research, the importance of model organisms, and the history of C. elegans in genetic research. He also reflects on controversial comments made by Sydney Brenner, explores early genomics progress, and discusses his current work on devising a vaccine against hookworm.
Model organisms like C. elegans play a crucial role in biology research, providing insights into general biological principles.
Genomics has transformed the study of model organisms, revealing similarities to human DNA and enabling investigations into shared genetic pathways and functions.
Advancements in sequencing technology have led to more accurate and precise understanding of model organism genomes, enhancing our ability to study and interpret their biological mechanisms.
Deep dives
The significance of model organisms in biology
Model organisms play a crucial role in biology research, providing insights into general biological principles. These organisms, such as fruit flies and nematode worms like C. elegans, are chosen for their simplicity, ease of study, and ability to breed quickly. They are used to study various biological processes, including development, genetics, and protein coding. With the advances in genomic technology, the genomes of model organisms have been sequenced and analyzed, revealing similarities to human DNA and shedding light on evolutionary relationships. Model organisms continue to be valuable tools for understanding fundamental biological processes.
The importance of genomics in understanding model organisms
Genomics has played a transformative role in studying model organisms like C. elegans. The ability to sequence and analyze the genomes of these organisms has provided valuable information about gene structure, protein coding, and regulatory elements. The C. elegans genome, for example, consists of approximately 100.3 million base pairs, with about one-sixth of the genome being repetitive DNA. Roughly the same amount of DNA in humans is involved in protein coding. Additionally, genomics has allowed researchers to identify similarities between model organism genomes and human genomes, enabling further investigations into shared genetic pathways and functions.
Advancements in sequencing technology and genome revision
Advancements in sequencing technology have led to more accurate and comprehensive genome sequencing of model organisms. For instance, the complete genome of C. elegans has been revised and improved multiple times. With the use of long-read sequencing technologies, gaps and inaccuracies in the original genome were identified and addressed. This has resulted in a more precise understanding of the genetic content of C. elegans, including the discovery of an additional 2 megabases of DNA. The continuous refinement of model organism genomes enhances our ability to study and interpret their biological mechanisms, providing valuable insights into various aspects of biology.
Working towards a hookworm vaccine
Eric, along with a team, is working on developing a vaccine for hookworm, a parasitic nematode that infects hundreds of millions of people globally. They started by sequencing the hookworm genome and identifying potential vaccine targets. After several years, they have successfully tested over 30 proteins for their vaccine efficacy. The project holds the promise of a future vaccine that could prevent hookworm infections and alleviate human suffering.
The future of synthetic biology
Eric expresses his belief that the next major frontier in biology will be the ability to build living organisms from scratch using synthetic biology. He mentions the ongoing project to create an artificial yeast cell as an example. Considering the simplicity and well-characterized genome of C. elegans, Eric thinks it could be an excellent model organism for synthetic biology experiments beyond simple prokaryotes. He envisions a future where organisms can be genetically engineered and customized to study fundamental biological processes.
Today Razib talks to geneticist Erich Schwarz, a Research Professor in the Department of Molecular Biology and Genetics at Cornell University since 2012. Schwarz has a molecular biology degree from Harvard and a Ph.D. from Caltech. After working with the fruit fly Drosophila melanogaster in graduate school, he switched to the nematode Caenorhabditis elegans, and has continued studying nematodes ever since. After helping to found the C. elegans genome database WormBase (wormbase.org) in the early 2000s, he began sequencing and characterizing the genomes of several nematode worms other than C. elegans, either because they are biologically informative or because they are worldwide parasites. His current work includes using the genome of Ancylostoma ceylanicum to help devise an anti-hookworm vaccine.
Schwarz explains why C. elegans, often called “the worm,” has been so useful in developmental and molecular genetics, and its role in the career of the late Nobel laureate Sydney Brenner. With a simple anatomical structure, every single one of the 1,000 cells of C. elegans has been mapped and detailed. Despite its small size, this organism has spawned a research community of thousands, documented in Andrew Brown’s In the Beginning Was the Worm: Finding the Secrets of Life in a Tiny Hermaphrodite. In the age of hundreds of thousands of human genomes, Schwarz explains the decades-long period in the late 20th century when biological research was dominated by “model organisms,” simple and easy-to-experiment-on animals, plants and bacteria that could eloquently and plainly elucidate universal and essential mechanisms of function and structure.
Razib and Schwarz also discuss the future of model organisms in a genomic future, when high-throughput data analysis can supercharge decades-long experimental projects. Ultimately, the future is not likely to see model organisms set aside, but rather to witness them merged into the broader research community in human and medical genomics which has been driving technological changes in sppedspeed and volume of data collection.
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