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Gonzalez, G. A.

Publications and source records attributed to Gonzalez, G. A..

3 recordsLinked to original sources

Genome modeling and design across all domains of life with Evo 2

All of life encodes information with DNA. While tools for sequencing, synthesis, and editing of genomic code have transformed biological research, intelligently composing new biological systems would also require a deep understanding of the immense complexity encoded by genomes. We introduce Evo 2, a biological foundation model trained on 9.3 trillion DNA base pairs from a highly curated genomic atlas spanning all domains of life. We train Evo 2 with 7B and 40B parameters to have an unprecedented 1 million token context window with single-nucleotide resolution. Evo 2 learns from DNA sequence alone to accurately predict the functional impacts of genetic variation--from noncoding pathogenic mutations to clinically significant BRCA1 variants--without task-specific finetuning. Applying mechanistic interpretability analyses, we reveal that Evo 2 autonomously learns a breadth of biological features, including exon-intron boundaries, transcription factor binding sites, protein structural elements, and prophage genomic regions. Beyond its predictive capabilities, Evo 2 generates mitochondrial, prokaryotic, and eukaryotic sequences at genome scale with greater naturalness and coherence than previous methods. Guiding Evo 2 via inference-time search enables controllable generation of epigenomic structure, for which we demonstrate the first inference-time scaling results in biology. We make Evo 2 fully open, including model parameters, training code, inference code, and the OpenGenome2 dataset, to accelerate the exploration and design of biological complexity.

genomics↗

A split-GAL4 driver line resource for Drosophila CNS cell types

Techniques that enable precise manipulations of subsets of neurons in the fly central nervous system have greatly facilitated our understanding of the neural basis of behavior. Split-GAL4 driver lines allow specific targeting of cell types in Drosophila melanogaster and other species. We describe here a collection of 3060 lines targeting a range of cell types in the adult Drosophila central nervous system and 1373 lines characterized in third-instar larvae. These tools enable functional, transcriptomic, and proteomic studies based on precise anatomical targeting. NeuronBridge and other search tools relate light microscopy images of these split-GAL4 lines to connectomes reconstructed from electron microscopy images. The collections are the result of screening over 77,000 split hemidriver combinations. Previously published and new lines are included, all validated for driver expression and curated for optimal cell type specificity across diverse cell types. In addition to images and fly stocks for these well-characterized lines, we make available 300,000 new 3D images of other split-GAL4 lines.

neuroscience↗

Degradation and bioconversion of complex municipal solid waste streams into human biotherapeutics and biopolymers

The use of biomass and organic waste as a feedstock for the production of fuels, chemicals and materials offers great potential to support the transition to net-zero and circular economic models. However, such renewable feedstocks are often complex, highly heterogeneous, and subject to geographical and seasonal variability, creating supply-chain inconsistency that impedes adoption. Towards addressing these challenges, the development of engineered microorganisms equipped with the ability to flexibly utilise complex, heterogenous substrate compositions for growth and bio-production would be greatly enabling. Here we show through careful strain selection and metabolic engineering, that Pseudomonas putida can be employed to permit efficient co-utilisation of highly heterogeneous substrate compositions derived from hydrolysed mixed municipal-like waste fractions, with remarkable resilience to compositional variability. To further illustrate this, one pot enzymatic pre-treatments of the five most abundant, hydrolytically labile, mixed waste feedstocks was performed - including food, plastic, organic, paper and cardboard, and textiles - for growth and synthesis of exemplar bio-products by engineered P. putida. Finally, prospective life cycle assessment and life cycle costing illustrated the climate change and economic advantage, respectively, of using the waste-derived feedstock for biomanufacturing compared to conventional waste treatment options. This work demonstrates the potential for expanding the treatment strategies for mixed municipal waste to include engineered microbial bio-production platforms that can accommodate variability in feedstock inputs to synthesise a range of chemical and material outputs.

synthetic biology↗