Research
We study RNA biology, using tools from both computational and experimental genomics.
We aim to uncover general principles of post-transcriptional RNA regulation in biological systems, by investigating these questions in the context of cell-state transition and animal development.
The RNA content of cells defines their molecular machinery and thus their properties. Different cells express different genes.
Living cells has the remarkable ability to compute accurate levels of each type of RNA at each time and place, and change it in responses to both external and internal signals to enable cell state transitions.
When cells change their identity, it require both production of new RNAs and removal of pre-existing RNAs that encoded the previous identity.
Much like erasing the board to write down new ideas.
We study how cells use RNA regulation to control these transitions.
Gene Regulation
Cells control each RNA molecule throughout its life-cycle: from its 'birth' by transcription, through its processing (e.g., splicing, polyadenylation), localization, translation, and to its ultimate 'death' by degradation. Together these encompass the dynamic mRNA life-cycle.
The mRNA life-cycle
Within this process, understanding the control on RNA molecules after their production has been neglected compared to transcriptional control.
New understanding of post-transcriptional gene regulation, a fundamental biological process, has far reaching implications throughout biology: from disease mechanisms to RNA-based therapeutics.
The tools and technologies we build help decode post-transcriptional RNA regulation across many systems and processes, and provide new tools to manipulate and design RNA molecules.
RNA biology
RNA molecules play a dual function both as carriers of genetic information, and as functional components of cellular machinery.
We aim to systematically decipher layers of the RNA regulatory code, and to understand their physiological implications on cellular transitions. We use this understanding in order to develop models that predict RNA regulation within cells.
The mRNA cis-regulatory code
Such models are highly useful to uncover the impact of genetic variations, and to improve bioengineering of RNA molecules for example in the context of mRNA-based therapeutics.
Embryonic development
Animal development is one of the most spectacular transformations in biology: a single-celled egg transforms into a complex animal, with many different cell types, tissues and organs.
Thus, embryonic cells undergo complex cell-state transitions. Post-transcriptional gene regulation is critical for cell-state transitions during embryonic development.
The "maternal-to-zygotic" transition is one of the earliest cell-state transitions in embryos.
Zebrafish development and the "maternal-to-zygotic" transition
Early embryos of all animals are transcriptionally silent, and exclusively rely on maternal RNAs and proteins for functionality. But further development requires a massive degradation of old maternal messages and production of new zygotic mRNAs to replace them. This unique regulation provides a powerful system to study post-transcriptional events.
Understanding this process has many important implications in fertility and embryogenesis, including efforts to reprogram cells for regenerative medicine.
What is our approach?
Our lab combines computational and experimental work:
Computational big-data analysis, machine learning and statistical models to dissect large-scale genomic data, and predict system behavior and outcomes.
Experimental high-throughput technologies and analysis tools to systematically measure RNA regulation, with a global-view on regulation.
The zebrafish embryo model is a powerful experimental system to systematically investigate these questions.