Genetic Disease Research Branch


Systems Biology and Genome Engineering Section


B.S. California Institute of Technology, 2006

Ph.D. University of California at Berkley, 2012


Meru Sadhu is an Earl Stadtman Investigator and head of the Systems Biology and Genome Engineering section at the National Human Genome Research Institute. He obtained his Bachelor's degree from Caltech, and then did his doctoral studies at UC Berkeley with Jasper Rine. For his postdoc, Dr. Sadhu joined Leonid Kruglyak's lab at UCLA, to complement his background in classical genetics with training in quantitative genetics. He developed approaches to apply CRISPR technology to quantitative genetics questions, including using CRISPR to direct recombination, and also to examine in parallel the effects of thousands of specific genetic variants. In the Systems Biology and Genome Engineering Section, he plans to use these and other new methods to address important questions in genetics.

Scientific Summary

The Systems Biology and Genome Engineering Section's goal is to systematically understand the effects of genetic differences. Researchers in this section study genetic diversity across an expansive range, such as natural variation between individuals or between species, or novel genetic changes that they create. By studying the functional effects of these variants, section researchers work to learn principles of genome function.

Section researchers use genome engineering to direct activities such as genome editing or recombination, using budding yeast as a model organism. As the space of potential genetic variants is immense, the section's researchers study large numbers of genetic differences in parallel. They do this by using large-scale oligonucleotide synthesis to generate a diversity of instructions targeting desired modifications, in order to generate pools of cells containing thousands of unique genomic changes. In addition to existing genome engineering methods, the section is continually developing new approaches to further expand the genetic space that can be studied.


Sadhu MJ, Bloom JS, Day L, Siegel JJ, Kosuri S, Kruglyak L. Highly parallel genome variant engineering with CRISPR-Cas9. Nat Genet. 50(4):510-514. 2018.

Forsberg SK, Bloom JS, Sadhu MJ, Kruglyak L, Carlborg Ö. Accounting for genetic interactions improves modeling of individual quantitative trait phenotypes in yeast. Nat Genet. 49(4):497-503. 2017.

Sadhu MJ, Bloom JS, Day L, Kruglyak L. CRISPR-directed mitotic recombination enables genetic mapping without crosses. Science. 352(6289):1113-6. 2016.

Bloom JS, Kotenko I, Sadhu MJ, Treusch S, Albert FW, Kruglyak L. Genetic interactions contribute less than additive effects to quantitative trait variation in yeast. Nat Commun. 6:8712. 2015.

Sadhu MJ, Moresco JJ, Zimmer AD, Yates JR 3rd, Rine J. Multiple inputs control sulfur-containing amino acid synthesis in Saccharomyces cerevisiae. Mol Biol Cell. 25(10):1653-65. 2015.

Sadhu MJ, Guan Q, Li F, Sales-Lee J, Iavarone AT, Hammond MC, Cande WZ, Rine J. Nutritional control of epigenetic processes in yeast and human cells. Genetics. 195(3):831-44. 2013.

Zill OA, Scannell DR, Kuei J, Sadhu M, Rine J. Evolutionary analysis of heterochromatin protein compatibility by interspecies complementation in Saccharomyces. Genetics. 192(3):1001-14. 2012.

Nelson BR, Sadhu M, Kasemeier JC, Anderson LW, Lefcort F. Identification of genes regulating sensory neuron genesis and differentiation in the avian dorsal root ganglia. Dev Dyn. 229(3):618-29. 2004.