Biomedical Graduate Studies

Description of Research Expertise

Molecular mechanisms of epigenetic memory

Noncoding RNAs

Chromatin biochemistry

Genes and behavior

Keywords: chromatin, noncoding RNAs, epigenetics, Polycomb, ants.

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).

The Bonasio Lab is part of the Department of Cell and Developmental Biology and of the Penn Epigenetics Institute.

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)

Alessandro Scacchetti, Ph.D. — Postdoctoral Associate

Brigitte Baella — Undergraduate student 2017–2019

Kristin Ingvarsdottir, Ph.D. — Postdoctoral Associate 2014–2019

Chongsheng He, Ph.D. — Postdoctoral Associate 2014–2018

Lihong Sheng, Ph.D - Postdoctoral Associate 2016–2021