Researching the molecular mechanisms of epigenetic memory


Part of the Department of Cell and Developmental Biology and the Penn Epigenetics Institute. at the University of Pennsylvania in Philadelphia

Affiliated with graduate programs in Cell & Molecular Biology (G&E), Biochemistry and Molecular Biophysics, Genomics and Computational Biology, and Neuroscience

Since March 2021 also operating a German outpost in beautiful Freiburg im Breisgau
thanks to the Max Planck-von Humboldt Research Award 2020


WE ARE HIRING POSTDOCS in Philadelphia

Roberto Bonasio, Ph.D.

Professor Of Cell And Developmental Biology

Overview

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.

Areas of Research

- Molecular mechanisms of epigenetic memory
- Noncoding RNAs
- Chromatin biochemistry
- Genes and behavior

Education

- Laurea (Biotechnology) University Of Milan, 2000.
- PhD (Immunology) Harvard Medical School, 2006.

Projects

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 changes on 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).

Figure 1

The latter constitute the focus of our current research. A large fraction of the genome is transcribed into noncoding 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. 

Figure 2

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 and computational approaches to study both conventional systems (mammalian cells, fruit flies) and nonconventional model organisms, such as ants and planarians, which offer new, unexplored avenues to study epigenetics (Figure 3).

Figure 3

People

Bonasio Lab Team
Christopher, Tim

Tim Christopher

Lab Manager
Shields, Emily

Emily Shields, Ph.D.

Computational Scientist
Sorida, Masato

Masato Sorida, Ph.D.

Postdoc
Former JSPS fellow
Scacchetti, Alessandro

Alessandro Scacchetti, Ph.D.

Postdoc
Antonova, Aneliya

Aneliya Antonova, Ph.D.

Lab Manager & Staff Scientist
(Freiburg team)
Kuang, Huizi

Mohuizi Kuang

PhD Student
(IMPRS, Freiburg)
Moreno-Medina, Sandra

Sandra Moreno-Medina, Ph.D.

Postdoc
(Freiburg team)
Garcia, Segovia

Segovia Garcia

PhD Student (CAMB-DSRB)
NRSA Predoctoral Fellow
Reich, Lauren

Lauren Reich

PhD Student (CAMB-G&E)
NSF GR Fellow
Khan, Shagufta

Shagufta Khan, Ph.D.

Postdoc
Doherty, Johnny

Johnny Doherty

PhD Student (CAMB-G&E)
T32 trainee
Tran, Tuan

Tuan Tran, Ph.D.

Postdoc

Ten selected publications

(see complete list on PubMed or Google Scholar)

Scacchetti A, Shields EJ, Trigg NA, Lee GS, Wilusz J, Conine CC, Bonasio R. A ligation-independent sequencing method reveals tRNA-derived RNAs with blocked 3’ termini. Mol Cell July 29, 2024 (online).

GitHub repository for LIDAR analysis.

Sheng L, Shields EJ, Gospocic J, Sorida M, Ju L, Byrns CN, Carranza F, Berger SL, Bonini N, Bonasio R. Ensheathing glia promote increased lifespan and healthy brain aging. Aging Cell 22(5):e13803, May 2023.

Gospocic J*, Glastad KM*, Sheng L, Shields EJ, Berger SL✉, Bonasio R✉. Kr-h1 maintains distinct caste-specific neurotranscriptomes in response to socially regulated hormones. Cell 184(23):5807-5823, November 2021.

He C✉, Bozler J, Janssen KA, Wilusz JE, Garcia BA, Schorn AJ, Bonasio R✉. TET2 chemically modifies tRNAs and regulates tRNA fragment levels. Nature Structural & Molecular Biology 28(1):62-70, January 2021.

Sheng L*, Shields EJ*, Gospocic J, Glastad KM, Ratchasanmuang P, Berger SL, Raj A, Little S, Bonasio R. Social reprogramming in ants induces longevity-associated glia remodeling. Science Advances 6(34):eaba9869, August 2020.

Explore the ant brain at single-cell resolution with antSCout.

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. Nature Structural & Molecular Biology 26(3):237-247, March 2019.

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, June 2018.

Download our new ant genome assemblies.

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, Aug 2017.

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.

Browse the RBR-ID dataset.


ADDRESS

Perelman School of Medicine
University of Pennsylvania
3400 Civic Center Boulevard
Building 421, Philadelphia, PA 19104

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