Computer aided design methods for mammalian genome engineering

Computer Aided Design (CAD) software assists engineers in designing systems in-silico, thus reducing the time-to-market of a product and increasing the overall productivity. Recent advances in synthetic biology required the development of similar methods to streamline the design of biological systems, ranging from genes to pathways, to chromosomes. As part of the synthetic yeast project, we developed the first genome engineering software to redesign the 16 chromosomes of the baker’s yeast genome [1]. With the cost of DNA synthesis predicted to drop by 1000-fold in the next 10 years, engineering mammalian cells will become possible; however, algorithms and software to tackle these large-scale engineering projects are currently non-existent.

Here we aim to develop the computational framework to design and edit mammalian-scale chromosomes. The long-term goal is to establish a standard for genome design and data sharing to support large genome writing projects.

The student will develop efficient data structures, such as genome graphs, to add/recode/delete DNA elements in mammalian genomes, and data-fusion methods, such as deep neural networks, to automatically annotate synthetic genomic elements. He/she will also learn how to write reproducible analysis pipelines and deploy research software. The student will have the opportunity to collaborate with the Edinburgh Genome Foundry, the most advanced biofoundry in the world specialized in DNA assembly up to genome scale.

The ideal candidate has a background in computer science, computer engineering, mathematics, statistics, physics or related fields. He/she is strongly motivated to develop a competitive profile in research software engineering, machine learning, synthetic genomics, data science, sequence analysis, while working in a fast-paced environment.

• www.stracquadaniolab.org
• https://www.genomefoundry.org