Roberto Bonasio, Ph.D.
3400 Civic Center Boulevard
Philadelphia, PA 19104
Laurea (Biotechnology )
University of Milan, 2000.
Harvard Medical School, 2006.
Description of Research ExpertiseResearch Interests
Molecular mechanisms of epigenetic memory
Genes and behavior
Keywords: chromatin, noncoding RNAs, epigenetics, Polycomb, ants.
Description of Research
My laboratory studies the molecular mechanisms of epigenetic memory, which are key to a number of biological processes, including embryonic development, cancer, stem cell pluripotency, and brain function.
Epigenetics allows the inheritance of variation (phenotype) without changes in the DNA sequence (genotype). The fact that pluripotent embryonic stem cells, all sharing the same genome, differentiate into hundreds of cell types implies that information about cellular identity and transcriptional states must be stored somewhere within the cell but not in the primary DNA sequence. It has become apparent that this epigenetic information can be encoded in molecular signatures associated with chromatin, the complex of DNA, RNA, and proteins that packages the genome within the eukaryotic nucleus. These signatures include DNA methylation, histone “marks” and variants, higher-order chromatin structures, and chromatin-associated noncoding RNAs (Figure 1).
The latter constitute the focus of our current research. A large fraction of the genome is transcribed into RNAs that, despite lacking protein-coding potential, perform important regulatory functions. Like proteins, RNA molecules can fold into complex tertiary structures with elaborate surfaces and cavities that mediate highly specific molecular interactions and even catalyze biochemical reactions; like DNA, RNA can form Watson–Crick base pairs with other RNAs or with DNA itself (Figure 2). In other words, RNA is fluent in two languages: the elaborate three-dimensional discourse of proteins and the linear genetic code of DNA. Thus, it seems fitting that RNAs may act as a molecular bridge—an epigenetic “translator”—between chromatin-regulating proteins and the genome sequence. Understanding how noncoding RNAs affect the epigenetic states of cells and organisms will provide us with unprecedented access to the regulatory circuitry that makes multicellular life possible.
We and others have discovered that several chromatin-associated protein complexes bind to noncoding RNAs and that these interactions are essential for their proper recruitment and assembly on chromatin, but we have only scratched the surface of the intricate network of protein–RNA interactions in the nucleus and many questions on how noncoding RNAs regulate epigenetic processes at the molecular, cellular, and organismal level remain unanswered.
We approach these fundamental biological questions from both a mechanistic and a systems-level perspective. We combine traditional biochemistry and molecular biology with genome-wide approaches and computational biology and study both conventional systems (mammalian cells) and nonconventional model organisms, such as ants, which offer new, unexplored avenues to study epigenetics (Figure 3).
Tim Christopher — Lab Manager
Janko Gospocic, Ph.D. — Postdoctoral Associate
Robert Warneford-Thomson — PhD student (BMB)
Emily Shields, Ph.D. — Postdoctoral Associate
Lihong Sheng, Ph.D. — Postdoctoral Associate
Ana Petracovici — PhD student (CAMB/G&E)
Tali Reiner Brodetzki — Postdoctoral Associate
Julianna Bozler — Postdoctoral Fellow
Julia Tasca — PhD student (BMB)
Brigitte Baella — Undergraduate student 2017–2019
Kristin Ingvarsdottir, Ph.D. — Postdoctoral Associate 2014–2019
Chongsheng He, Ph.D. — Postdoctoral Associate 2014–2018
Selected PublicationsYan Q*, Shields EJ*, Bonasio R†, Sarma K†: Mapping native R-loops genome-wide with a targeted nuclease approach. Cell Rep Oct 2019 Notes: Co-corresponding author. Kavitha Sarma (Wistar) and conceived this project together. My computational student Emily Shields did all the bioinformatic work and is co-first author. We wrote the manuscript and generated figures together.
Zhang Q*, McKenzie NJ*, Warneford-Thomson R*, Gail EH, Flanigan SF, Owen BM, Lauman R, Levina V, Garcia BA, Schittenhelm RB, Bonasio R†, Davidovich C†: RNA exploits an exposed regulatory site to inhibit the enzymatic activity of PRC2. Nat Struct Mol Biol 26(3): 237-247, Mar 2019 Notes: Co-corresponding author. My biochemistry student contributed all in vivo RNA mapping expeirments and is joint first author.
Shields EJ, Sheng L, Weiner AK, Garcia BA, Bonasio R: High-Quality Genome Assemblies Reveal Long Non-coding RNAs Expressed in Ant Brains. Cell Reports 23(10): 3078-3090, Jun 2018.
Gospocic J, Shields EJ, Glastad KM, Lin Y, Penick CA, Yan H, Mikheyev AS, Linksvayer TA, Garcia BA, Berger SL, Liebig J, Reinberg D, Bonasio R: The Neuropeptide Corazonin Controls Social Behavior and Caste Identity in Ants. Cell 170(4): 748-759.e12, Aug 2017 Notes: I discovered caste-specific expression of corazonin at the end of my postdoc with Danny Reinberg, by analyzing a pilot RNA-seq experiment. All other experiments, including most RNA-seq, behavior, peptide injections, knockdowns, and fly genetics were done in my laboratory.
Yan H, Opachaloemphan C, Mancini G, Yang H, Gallitto M, Mlejnek J, Leibholz A, Haight K, Ghaninia M, Huo L, Perry M, Slone J, Zhou X, Traficante M, Penick CA, Dolezal K, Gokhale K, Stevens K, Fetter-Pruneda I, Bonasio R, Zwiebel LJ, Berger SL, Liebig J, Reinberg D: An Engineered orco Mutation Produces Aberrant Social Behavior and Defective Neural Development in Ants. Cell 170(4): 736-747.e9, Aug 2017.
Bose Daniel A, Donahue Greg, Reinberg Danny, Shiekhattar Ramin, Bonasio Roberto, Berger Shelley L: RNA Binding to CBP Stimulates Histone Acetylation and Transcription. Cell 168(1-2): 135-149.e22, Jan 2017 Notes: My lab provided technical help with protein–RNA biochemistry and crosslinking assays and I participated extensively in the writing of the manuscript.
He C, Sidoli S, Warneford-Thomson R, Tatomer DC, Wilusz JE, Garcia BA, Bonasio R: High-resolution mapping of RNA-binding regions in the nuclear proteome of embryonic stem cells. Molecular Cell 64(2): 416–30, Oct 2016.
Kaneko S, Son J, Shen SS, Reinberg D, Bonasio R: PRC2 binds active promoters and contacts nascent RNAs in embryonic stem cells. Nat Struct Mol Biol 20(11): 1258-64, Nov 2013 Notes: This study was performed in the Reinberg lab but because of my senior role in designing, performing, and analyzing the experiments, as well as writing the manuscript, I am the senior co-corresponding author on the paper.
Bonasio R, Zhang G, Ye C, Mutti NS, Fang X, Qin N, Donahue G, Yang P, Li Q, Li C, Zhang P, Huang Z, Berger SL, Reinberg D, Wang J, Liebig J: Genomic comparison of the ants Camponotus floridanus and Harpegnathos saltator. Science 329(5995): 1068-71, Aug 2010.
Bonasio R, Tu S, Reinberg D: Molecular signals of epigenetic states. Science 330(6004): 612-6, Oct 2010.