Genome Project-write

Genome Project-write

Genome Project-write (GP-write) is an open international research project that plans to reduce costs of engineering and testing large genomes in cell lines for the purpose of understanding the blueprint of life. GP-write includes whole genome engineering of human cell lines and other organisms that have relevance to agriculture and public health.

All edits by  Meredith Hanel 

Edits on 7 Jul, 2020
Meredith Hanel
Meredith Hanel edited on 7 Jul, 2020
Edits made to:
Article (-4 characters)
Article

Harris Wang at Columbia University plans to produce human cell lines that have biosynthetic pathways for production of essential amino acids and vitamins that humans must otherwise obtain from diet. One goal of the project is to use the cells to combat malnutritional conditions, with the cells are also proposed to have utility in studying biochemistry in mammalian development and relationships between nutrition and aging processes. Another application of biosynthetic pathway enhanced human cell lines is as an alternative to mammalian cell lines for production of biomolecules for research and as therapeutics. The modified prototrophic human cells could potentially be grown with less expensive growth media . Boeke and Wang received $500,00 from Defense Advanced Research Projects Agency (DARPA) for this project.

Edits on 26 Jun, 2020
Meredith Hanel
Meredith Hanel edited on 26 Jun, 2020
Edits made to:
Article (+38/-9 characters)
Article
HGP-write
Human Genome Project-Write (HGP-write)
Edits on 4 Jun, 2019
Meredith Hanel
Meredith Hanel edited on 4 Jun, 2019
Edits made to:
Related Topics (+1 topics)
Related Topics
Edits on 23 May, 2019
Meredith Hanel
Meredith Hanel edited on 23 May, 2019
Edits made to:
Article (+603 characters)
Article

GP-write will enable better engineering of biology, which could have applications to combat a wide range of challenges including energy production and climate change. GP-write is expected to accelerate research and development in areas like production of food and materials. June Medford from Colorado State University has ideas to engineer plants to filter water or detect chemicals. Harris Wang at Columbia University is investigating the manipulation of genomes of the human microbiome which could potentially lead to modified gut microbes that produce essential amino acids, influence metabolism to treat obesity or secrete compounds to treat irritable bowel syndrome.

The Synthetic Yeast Genome project (Yeast 2.0 or Sc2.0) will be the first eukaryotic genome to be synthesized, and as human are eukaryotic as well, it provides groundwork for synthetic human genome projects. Genome writing in yeast could also lead to new uses for yeast, such as production of biofuel or other useful compounds.

Meredith Hanel
Meredith Hanel edited on 23 May, 2019
Edits made to:
Article (+1478 characters)
Further reading (+1 rows) (+3 cells) (+193 characters)
Article
Purpose

The main purpose of GP-write is to better understand the human genome and other genomes in order to benefit from that knowledge. Despite large-scale studies to interpret the human genome, such as HapMap, Encyclopedia of DNA Elements (ENCODE) and genome-wide association studies (GWAS), the understanding of the human genome is considered far from complete. Many scientists believe that by building genomes, they will be better understood because building genomes allows genomes to be tested. The manifesto for the synthetic biology field has been borrowed from physicist Richard Feynman who said, “What I cannot create, I cannot understand”.

Potential benefits to humanity which could come out of GP-write projects on human cells include, growing transplantable human organs, engineering cell lines immune to viruses, engineering cancer resistance into therapeutic cell lines, improving productivity and cost of producing vaccines and pharmaceuticals with human cells.

June Medford from Colorado State University has ideas to engineer plants to filter water or detect chemicals. Harris Wang at Columbia University is investigating the manipulation of genomes of the human microbiome which could potentially lead to modified gut microbes that produce essential amino acids, influence metabolism to treat obesity or secrete compounds to treat irritable bowel syndrome.

...

Jasper Rine at University of California has a pilot project with one aspect investigating methods for safety and containment of synthetic genomes or prevent synthetic organisms from hybridizing with natural organisms if they were to be used in agriculture. Methods will be developed and investigated that would prevent survival of recombinants from such hybrids. The project would involve scrambling chromosomes and the utilization of balancer chromosomes similar to those used in the breeding of Drosophila (fruit flies) for genetics research but done in yeast. Synthetic yeast genome Sc2.0 technology would be used. Toxin-antidote combinations inserted into chromosomes that cause the cell to die when separated would be another route of investigation.

...

Harris Wang at Columbia University plans to produce human cell lines that have biosynthetic pathways for production of essential amino acids and vitamins that humans must otherwise obtain from diet. One goal of the project is to use the cells to combat malnutritional conditions, with the cells are also proposed to have utility in studying biochemistry in mammalian development and relationships between nutrition and aging processes. Another application of biosynthetic pathway enhanced human cell lines is as an alternative to mammalian cell lines for production of biomolecules for research and as therapeutics. The modified prototrophic human cells could potentially be grown with less expensive growth media . Boeke and Wang received $500,00 from Defense Advanced Research Projects Agency (DARPA) for this project.

Further reading

Title
Author
Link
Type
Date

A Grand Challenge for Genome Engineering: GP-write | Columbia University Department of Systems Biology

Web

Meredith Hanel
Meredith Hanel approved a suggestion from Golden's AI on 23 May, 2019
Edits made to:
Article (+14/-14 characters)
Article

Liam Holt at University of California, Berkeley, leads a pilot project to use synthetic biology to map the cell signalingcell signaling pace of the seven core developmental pathways (Hedgehog, Wnt, TGF-beta, receptor tyrosine kinase, Notch, JAK/STAT and nuclear hormone pathways) to differentiation space which is the range of possible cell states in the progression of stem cells to differentiated cells. The goal is to develop a genetic toolbox for precise temporal modulation of the seven pathways using optiogenetic or chemical control, along with a complimentary toolbox of reporters to profile cell phenotypes. It is expected that the tools will be applicable to controlling the use HGP2 (Human Genome Project 2) cell lines in cell therapies, tissue replacement or organ transplants.

Meredith Hanel
Meredith Hanel approved a suggestion from Golden's AI on 23 May, 2019
Edits made to:
Article (+13/-13 characters)
Article

Jeffrey Way and Pamela SilverPamela Silver, both of Harvard, are leading a project proposing to build two regions of the human genome each of about 1 megabase in size as a human artificial chromosome (HAC). The genomic sequences would be assembled in yeast and technology would be developed to move them into human cells. The system would be used to study mechanisms of long-range gene expression and for engineering humans for an optimized antiviral immune response.

Meredith Hanel
Meredith Hanel approved a suggestion from Golden's AI on 23 May, 2019
Edits made to:
Article (+11/-11 characters)
Article

Jasper RineJasper Rine at University of California has a pilot project with one aspect investigating methods for safety and containment of synthetic genomes or prevent synthetic organisms from hybridizing with natural organisms if they were to be used in agriculture. Methods will be developed and investigated that would prevent survival of recombinants from such hybrids. The project would involve scrambling chromosomes and the utilization of balancer chromosomes similar to those used in the breeding of Drosophila (fruit flies) for genetics research but done in yeast. Synthetic yeast genome Sc2.0 technology would be used. Toxin-antidote combinations inserted into chromosomes that cause the cell to die when separated would be another route of investigation.

Meredith Hanel
Meredith Hanel approved a suggestion from Golden's AI on 23 May, 2019
Edits made to:
Article (+13/-13 characters)
Article

The main portion of the details of the construction of five out of 16 chromosomes that make up the yeast (Saccharomyces cerevisiae) genome, lead by Jef Boeke and his Sc2.0 team was published in Science in 2017. To build their first chromosome, which is the shortest, took nearly 10 years. It took less than three years to generate the next five chromosomes, which includes the longest one. The blueprints for the chromosomes are written using a computer program and analyzed by biologists and then they are broken into shorter manageable segments. Segments are synthesized in DNA synthesisDNA synthesis labs and then they are joined together using a technique developed by Boeke and undergraduates who took his “build-a-genome” course at Johns Hopkins. The new synthetic genomic material is injected into yeast cells and swaps in for the native DNA by homologous recombination.

Meredith Hanel
Meredith Hanel approved a suggestion from Golden's AI on 23 May, 2019
Edits made to:
Article (+5/-5 characters)
Article

Yasunori Aizawa of the Tokyo Institute of Technology, JapanJapan, has a pilot project intended to screen for essential introns and retroelements in human cells, mouse and fruit fly in a systematic manner. One and then both alleles of each gene will be replaced with synthetic versions that lack introns and upstream and downstream intergenic regions. Transcriptional, epigenetic status will be compared between native and synthetic versions. Functional analysis of the genes and pathways will be performed when alleles are replaced with the synthetic version. To understand any changes that occur, introns and retroelements will be systematically placed back into the synthetic gene to identify which DNA elements are significant. Their technology includes the development are a “scar-free” marker, useful for others in the GP-write community and development of a protocol for CRISPR/Cas9 usage for promoting the native and synthetic swapping. It is expected that knowing which introns and retroelements are dispensable will allow the synthesis of more compact and simple gene structures, reducing cost and labor in future genome synthesis projects.

Meredith Hanel
Meredith Hanel approved a suggestion from Golden's AI on 23 May, 2019
Edits made to:
Article (+31/-31 characters)
Article

Todd Kuiken of North Carolina State UniversityNorth Carolina State University and Gigi Gronvall of Johns Hopkins Center for Health and Security are leading a pilot project that aims to gain understanding and anticipate the governance issues around GP-write. The project will include local, state and national oversight regimes for the research stage and for approval of products or applications that come out of GP-write. Since public support is needed to enable and sustain funding, public dialogue and outreach programs will be established that inform and incorporate the views of the public into the research program.

Meredith Hanel
Meredith Hanel approved a suggestion from Golden's AI on 23 May, 2019
Edits made to:
Article (+10/-10 characters)
Article

Jeffrey Way and Pamela Silver, both of Harvard, are leading a project proposing to build two regions of the human genome each of about 1 megabase in size as a human artificial chromosome (HAC). The genomic sequences would be assembled in yeast and technologytechnology would be developed to move them into human cells. The system would be used to study mechanisms of long-range gene expression and for engineering humans for an optimized antiviral immune response.

Meredith Hanel
Meredith Hanel approved a suggestion from Golden's AI on 23 May, 2019
Edits made to:
Article (+10/-10 characters)
Article

Jasper Rine at University of California has a pilot project with one aspect investigating methods for safety and containment of synthetic genomes or prevent synthetic organisms from hybridizing with natural organisms if they were to be used in agriculture. Methods will be developed and investigated that would prevent survival of recombinants from such hybrids. The project would involve scrambling chromosomes and the utilization of balancer chromosomes similar to those used in the breeding of DrosophilaDrosophila (fruit flies) for genetics research but done in yeast. Synthetic yeast genome Sc2.0 technology would be used. Toxin-antidote combinations inserted into chromosomes that cause the cell to die when separated would be another route of investigation.

Meredith Hanel
Meredith Hanel approved a suggestion from Golden's AI on 23 May, 2019
Edits made to:
Article (+10/-10 characters)
Article

Liam Holt at University of California, Berkeley, leads a pilot project to use synthetic biology to map the cell signaling pace of the seven core developmental pathways (Hedgehog, Wnt, TGF-beta, receptor tyrosine kinase, Notch, JAK/STAT and nuclear hormone pathways) to differentiation space which is the range of possible cell states in the progression of stem cellsstem cells to differentiated cells. The goal is to develop a genetic toolbox for precise temporal modulation of the seven pathways using optiogenetic or chemical control, along with a complimentary toolbox of reporters to profile cell phenotypes. It is expected that the tools will be applicable to controlling the use HGP2 (Human Genome Project 2) cell lines in cell therapies, tissue replacement or organ transplants.

Meredith Hanel
Meredith Hanel approved a suggestion from Golden's AI on 23 May, 2019
Edits made to:
Article (+17/-17 characters)
Article

Liam Holt at University of California, Berkeley, leads a pilot project to use synthetic biologysynthetic biology to map the cell signaling pace of the seven core developmental pathways (Hedgehog, Wnt, TGF-beta, receptor tyrosine kinase, Notch, JAK/STAT and nuclear hormone pathways) to differentiation space which is the range of possible cell states in the progression of stem cells to differentiated cells. The goal is to develop a genetic toolbox for precise temporal modulation of the seven pathways using optiogenetic or chemical control, along with a complimentary toolbox of reporters to profile cell phenotypes. It is expected that the tools will be applicable to controlling the use HGP2 (Human Genome Project 2) cell lines in cell therapies, tissue replacement or organ transplants.

Meredith Hanel
Meredith Hanel edited on 23 May, 2019
Edits made to:
Timeline (+1 events) (+605 characters)
Article (+1047 characters)
Documentaries, videos and podcasts (+2 rows) (+4 cells) (+208 characters)
Article

The main portion of the details of the construction of five out of 16 chromosomes that make up the yeast (Saccharomyces cerevisiae) genome, lead by Jef Boeke and his Sc2.0 team was published in Science in 2017. To build their first chromosome, which is the shortest, took nearly 10 years. It took less than three years to generate the next five chromosomes, which includes the longest one. The blueprints for the chromosomes are written using a computer program and analyzed by biologists and then they are broken into shorter manageable segments. Segments are synthesized in DNA synthesis labs and then they are joined together using a technique developed by Boeke and undergraduates who took his “build-a-genome” course at Johns Hopkins. The new synthetic genomic material is injected into yeast cells and swaps in for the native DNA by homologous recombination.

The principles for Sc2.0 genome design are to maintain a “wild-type” phenotype while introducing genetic flexibility and reducing sources of genomic instability. The genetic code for Sc2.0 chromosomes have TAG stop codons changed to TAA stop codons. There are loxPsym sites as part of the inducible evolution system called SCRaMbLE. Repeat elements are removed as well as many introns. Transfer RNA (tRNA) genes are relocated to a “neochromosome”. Wild-type DNA and synthetic DNA are distinguished by PCRTags, which are short recoded sequences within the open reading frames (ORF) that can be assayed by PCR reactions. DNA sequence base substitutions within ORFs introduce or remove recognition sites for enzymes in order to facilitate assembly of synthetic chromosomes. For Sc2.0 scientists used BioStudio, an open-source design platform developed for eukaryotic genome design. BioStudio coordinates design modifications at both nucleotide and genome scales and enforces version control to track edits systematically.

Documentaries, videos and podcasts

Title
Date
Link

Andrew Hessel is Introducing the 2nd Human Genome Project | History NOW

HGP-write: A Grand Challenge for Genome Engineering

Timeline

March 10, 2017

Design of a synthetic yeast genome

Sarah M. Richardson1,2,*,‖, Leslie A. Mitchell2,3,‖, Giovanni Stracquadanio1,2,4,‖, Kun Yang1,2,‖, Jessica S. Dymond2,†, James E. DiCarlo2,‡, Dongwon Lee1,§, Cheng Lai Victor Huang2, Srinivasan Chandrasegaran5, Yizhi Cai2,6, Jef D. Boeke2,3,#, Joel S. Bader1,2,#

Science 10 Mar 2017:

Vol. 355, Issue 6329, pp. 1040-1044

DOI: 10.1126/science.aaf4557

We describe complete design of a synthetic eukaryotic genome, Sc2.0, a highly modified Saccharomyces cerevisiae genome reduced in size by nearly 8%, with 1.1 megabases of the synthetic genome deleted, inserted, or altered.

Edits on 23 May, 2019
Meredith Hanel
Meredith Hanel edited on 23 May, 2019
Edits made to:
Article (+837/-210 characters)
Further reading (+1 rows) (+3 cells) (+166 characters)
Article

The main portion of the details of the construction of five out of 16 chromosomes that make up the yeast (Saccharomyces cerevisiae) genome, lead by Jef Boeke and his Sc2.0 team was published in Science in 2017.

The main portion of the details of the construction of five out of 16 chromosomes that make up the yeast (Saccharomyces cerevisiae) genome, lead by Jef Boeke and his Sc2.0 team was published in Science in 2017. To build their first chromosome, which is the shortest, took nearly 10 years. It took less than three years to generate the next five chromosomes, which includes the longest one. The blueprints for the chromosomes are written using a computer program and analyzed by biologists and then they are broken into shorter manageable segments. Segments are synthesized in DNA synthesis labs and then they are joined together using a technique developed by Boeke and undergraduates who took his “build-a-genome” course at Johns Hopkins. The new synthetic genomic material is injected into yeast cells and swaps in for the native DNA.

Further reading

Title
Author
Link
Type
Date

Yeast 2.0--connecting the dots in the construction of the world's first functional synthetic eukaryotic genome

Web

Meredith Hanel
Meredith Hanel edited on 23 May, 2019
Edits made to:
Article (+7 characters)
Article

GP-write is being implemented through an independent non-profit organization called the Center of Excellence for Engineering Biology (CEEB). The non-profit is managing the initial planning and coordination which involves supporting multi-institutional and interdisciplinary research teams working in an integrated fashion. The organization is also engaged in public outreach.

Meredith Hanel
Meredith Hanel edited on 23 May, 2019
Edits made to:
Article (+337 characters)
Article

Labcyte, a biotechnology tools company, has an agreement with the CEEB which includes providing preferred pricing and support to researchers at qualified laboratories affiliated with and contributing to the GP-write mission and goals. Labcyte will also provide selected researchers with early access to certain newly developed products.

Meredith Hanel
Meredith Hanel edited on 22 May, 2019
Edits made to:
Article (+793/-23 characters)
Article

Pilot projects are evaluated with the Scientific Executive Committee. GP-write supports scientists submitting pilot projects with letters of recommendation until the project is fully funded. In the future GP-write has the goal of directly financially support pilot projects. Scientists can apply for funding through their university with GP-write providing a letter of recommendation or scientists can partner with the Center of Excellence to apply for funding.

...
Approved pilot projects
Projects
...
Approved pilot projects
...
Synthetic regulatory genomics

Matthew Maurano of NYU Langone Health has a pilot project to use synthetic approach to study regulatory genomics. The project aims to address the gap in the understanding of the gene regulatory role of genetic variants that lie in non-coding regions of the human genome.

Golden logo
Text is available under the Creative Commons Attribution-ShareAlike 4.0; additional terms apply. By using this site, you agree to our Terms & Conditions.