Jonathan Gootenberg

The Abudayyeh-Gootenberg lab is focused on the understanding and engineering of programmability in biology. These programmable systems, inspired by natural diversity, provide precise control over genomes, transcriptomes, and cellular identity, and are applied by the lab to explore basic biological questions and create new therapeutic approaches. The lab has a particular focus on using these techniques in genetic diseases, cancer, and diseases of age, as well as to engineer new methods for basic biology. This vision is captured by multiple threads in the lab:

Engineering of Programmable Therapeutics: The lab leverages programmable biology to develop new methods for manipulating DNA and RNA within cells, restricting therapies to specific cell types or cell states, and delivering nucleic acid therapeutics in vivo. These technologies include approaches for flexible kilobase DNA insertion into the genome, manipulation of transcriptomes via RNA splicing, responsive sensing elements for controlling expression, and tissue-specific lipid nanoparticle delivery technologies. In combination, these different methods provide a comprehensive toolbox for the next generation of programmable medicines.

Understanding and programming cell fate: The capacity to engineer precise cell state transitions is a critical need to both understand the underlying mechanisms controlling cell fate decisions, as well as produce new cell states for disease modelling and therapeutics. The lab approaches these transitions through the lens of pooled screening approaches, coupling comprehensive libraries covering transcription factors, secreted proteins, or all the coding genes in the genome, with high-content single-cell readouts. This data can further be used to train predictive models of perturbations, with the goal of generating in silico predictions of cell responses.

Rejuvenating aged cell populations: The lab applies these technologies to the profiling and reversal of age-associated changes in diverse tissues, including blood, hair, and muscle. Profiling primary tissues across a range of ages, we can build informative models of cellular age, which can be registered to organismal phenotypes. These signatures of aging can be then used as readouts for mechanism-based screens to discover additional pathways of aging and to nominate new interventions in age-associated disease.

Developing solutions for sustainability and climate change: Applying the programmability of biology to climate change and sustainability, the lab applies protein engineering to manufacturing, carbon capture, and bioremediation. These pressing issues are addressed by refining of proteins through directed evolution, machine learning-assisted design, and biological search.

These projects demonstrate the potential of programmability across biology to further our understanding of fundamental processes and revolutionize industries, from therapeutics to sustainability.