Table 2.
Approved GP-write pilot projects (by January 2018)
| Project title | Project goalsa | Project lead(s) |
|---|---|---|
| UltraSafe Cell Line | The project aims to generate an Ultrasafe cell line by altering roughly 1% of the human genome. Some key goals are: Virus and prion resistance, removal of transposable elements, recoding of triplet repeats, recoding to a human consensus sequence in regard to SNPs and indels, implementing the bespoke SCRaMbLE system beside further alterations. | Jef Boeke & George Church |
| High-throughput HAC Design to Test Connections Between Gene Expression, Location and Conformation | There is still a lack of understanding of the regulation of gene expression. The project will build two 1 mb regions of the human genome. The regions will be constructed as combinatorial libraries with different promoters and insulators to investigate ‘rules’ for optimal gene expression. | Pamela Silver & Jeffrey Way |
| Safety and Containment; Chromatin and Chromosome Structure | This project tries to solve two questions based on Sc2.0 strains and implement the results into GP-write. Firstly: how can hybridization with natural occurring strains or organisms be excluded? Second: what shapes the contact maps of chromosomes? The latter will be answered by analysing multiple SCRaMbLed Sc2.0 strains to investigate chromatin structure based on re-arranged chromosomes | Jasper Rine |
| Empirically Designing Genomically Recoded Human Cell Lines | Codon alteration is an important part of GP-write. The project aims to develop: Firstly, a rapid method for multiplex targeted genome modification; secondly, a respective rapid and robust screening system for living cells in 96-well format; thirdly, a strategy for rapid evaluation of heterogenic cell populations; and finally, a software to design the synthetic DNA fragments and evaluate viability of codon replacements. | Marc Lajoie |
| The Seven Signals Toolbox: Leveraging Synthetic Biology to Define the Logic of Stem-Cell Programming | Cell differentiation is mainly driven by seven signal types. This project aims to generate a toolbox which allows the in vitro differentiation of GP-write cell lines. This is a crucial step for future applications in the field of cell therapies, tissue replacement or transplantation of organs. | Liam Holt |
| Precision Human Genome Engineering of Disease-Associated Noncoding Variants | Efficient and precise engineering of the human genome is still a challenge. This project aims to create a complete pipeline for rapid engineering of human cells with an enrichment for homologous recombination repair. The project will also provide bioinformatic tools to optimize CRISPR based engineering. | Neville Sanjana |
| Synthesizing a Prototrophic Human Genome | This project postulates to introduce pathways for the nine amino acids and a variety of vitamins which cannot be synthesized by humans. These molecules derive from the diet. It investigates whether the milieu in the cell makes a prototrophic cell line feasible. If the project succeeds, further engineering would be performed and the first achievement would be a drastic cost reduction of cell line cultivation media. | Harris Wang |
| Through the Looking Glass: Anticipating and Understanding Governance Systems and the Public's Views on HGP-write | Including the publics view and governance systems into GP-write is an important step. This project will generate a dialogue between scientists and the public. Incorporation of the society will enable acceptance and support for GP-write. | Todd Kuiken & Gigi Gronvall |
| Synthetic Screening for Essential Introns and Retroelements in Human Cell and Animals | This project aims to perform systematic screenings of intron and retroelements in the genome. Combinatorial variants of chosen genes will be investigated in a diploid background. The outcome will indicate if the removal of these elements, like in Sc2.0, is feasible in GP-write. | Yasunori Aizawa |
| Isothermal Amplification Array | This project proposes a new method to synthesize DNA. It depends on two steps. Firstly: generation of short oligonucleotides by an isothermal amplification on an array. Secondly: the amplified oligonucleotides can anneal according to their design and nicks are sealed by a ligase. | Max Berry |
| Recombinase-Mediated Assembly | This project proposes a new method to assemble DNA fragments by utilizing a RecA-like recombinase (UvsX). The method should allow, with the Isothermal Amplification Array assembly from short oligos to chromosome-sized DNA, with a significant labour reduction. | Max Berry |
| Synthetic Regulatory Genomics | The project aims to study regulatory variations of non-coding regions. The project will use multi-edited regulatory DNA sequences and analyse their function with multiple techniques. This project will give deeper insights into non-coding regions of complex genomes. | Matt Maurano |
| Concepts & Ethics in GP-write: Understand, Question, Advance | This project aims to build a model for deep analysis of concepts and ethics in GP-write, and aims include the dynamics of science and society. It aims to expand collaborations between sciences and the humanities and provide proper education and training. | Jeantine Lunshof |
a
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