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Funding Update: Jul 27, 2010

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New Sequencing-Related NSF Grants, Awarded Jan. 1 — July 26, 2010

Acquisition of genomic and bioinformatic technology to promote research at the University of Puerto Rico

Start Date: July 1, 2010
Expires: June 30, 2013
Awarded Amount to Date: $637,664
Principal Investigators: Tomas Hrbek, Jose Garcia-Arraras, Maria Dominguez-Bello,
Humberto Ortiz-Zuazaga, Steven Massey
Sponsor: University of Puerto Rico-Rio Piedras

This award funds the purchase of a next-generation sequencing system for the University of Puerto Rico-Rio Piedras. The new sequencer will support a range of research projects investigating biodiversity in the neotropics. Areas of focus are environmental genomics, developmental genomics, evolutionary and ecological genomics, and bioinformatics.


Deciphering ionic current signatures of polymer transport through a nanopore

Start Date: Aug. 15, 2010
Expires: July 31, 2011
Awarded Amount to Date: $85,000
Principal Investigator: Aleksei Aksimentiev
Sponsor: University of Illinois at Urbana-Champaign

This award supports computational and theoretical research and education on translocation of polymers through nanopores. The research program investigates electric field-driven transport of a prototypical polymer DNA molecule through biological and synthetic nanopores and accompanying changes in co-passing ionic current used to characterize the transport by experiment. The principal investigator aims to provide a comprehensive physical description of polymer transport through biological and synthetic nanopores through an innovative modeling method that combines all-atom molecular dynamics, Brownian dynamics, and multiscale simulations. This method will preserve the atomic-level information of the molecular dynamics method, while capitalizing on the computational efficiency of the Brownian dynamics and multiscale methods. The approach will exploit the thousandfold difference in the time scales of ion and polymer transport. The process of DNA transport through a nanopore will be characterized in statistical terms. The obtained ensemble of DNA conformations will be used to compute the corresponding ionic current blockades. The final step of the approach is to take into account the electro-kinetic effect that couples the ionic current to the polymer conformation. The main difference of this approach from the coarse-grained models that have been proposed to date is in preserving the all-atom information about the structure of the solute and nanopore and determining the ionic current blockade to the experimental accuracy, according to the grant abstract. Combined with experimental methods, such predictive capability will greatly enhance utility of nanopores as tools to probe nanoscale systems and processes, according to the researchers.


Single-molecule study of biopolymers in complex solutions

Start Date: Aug. 15, 2010
Expires: July 31, 2011
Awarded Amount to Date: $96,181
Principal Investigator: Omar Saleh
Sponsor: University of California-Santa Barbara

This project will study the elasticity of single-stranded DNA molecules of various sequences in a variety of solution conditions, and quantify the effects of multivalent counterions and crowding agents on dynamic aspects of biopolymer structure. The research program is designed to result in clear, quantitative physical principles governing ionic biopolymer behavior in the kind of crowded, salt-rich environments encountered in biological cells. The principal investigator will directly quantify the physical parameters of single-stranded DNA of various sequences, and attempt to resolve conflicting results on the sequence-dependence of single-stranded DNA's local stiffness. He will investigate the ability of single-stranded DNA base-stacking to create rod-like statistical monomers. Rod-like polymers have been predicted, though not demonstrated, to have novel elasticity behaviors. Multivalent solution electrostatics represents a major unsolved theoretical problem, and this study of the effect of salts of various valencies will give clear data on complex issues of solution electrostatics. The approach will provide data that may validate or invalidate certain theories. All of the experiments are designed to help validate the link recently forged by the principal investigator and coworkers between the scaling picture of polymers and single-molecule stretching experiments.


The evolution of gene expression: molecular mechanisms and inheritance patterns revealed on a genomic scale with next-generation sequencing

Start Date: Aug. 1, 2010
Expires: July 31, 2011
Awarded Amount to Date: $277,698
Principal Investigator: Patricia Wittkopp
Sponsor: University of Michigan

This project will reveal the types of molecular changes responsible for the evolution of gene expression throughout the genome using the latest high-throughput sequencing technology. New computational tools will also be developed in the course of this work that will assist other researchers working on a variety of scientific questions.

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Efficient and accurate computation for high throughput sequencing related problems in population genomics

Start Date: July 1, 2010
Expires: June 30, 2011
Awarded Amount to Date: $78,716
Principal Investigator: Yufeng Wu
Sponsor: University of Connecticut

This project will develop accurate computational methods that are capable of analyzing large-scale high-throughput sequencing data for several population genomics problems. Problems of interest include inferring genotypes, correcting sequencing errors and detecting meiotic recombination, as well as searching for disease-causing rare gene variants and other emerging applications of high-throughput sequencing. A key difference between the proposed research and many existing methods is that the proposed approaches are explicitly designed for processing large amounts of high-throughput sequencing data. One particular focus is on applying combinatorial optimization techniques such as integer linear programming, which, the grantees note, is not well-known to biologists. Probabilistic models will also be used and integrated with optimization approaches to provide efficient and accurate solutions. The expected project outcome includes efficient algorithms for population genomics problems, related open-source software tools, and rigorous methodologies for both theoretical and empirical evaluation of the algorithms. The investigators note in the grant abstract that the work is also expected to contribute to the field of computer science, particularly in the area of string-matching algorithms and phylogenetic problems.


DNA discrimination using the synthetic hybrid nanopore

Start Date: July 1, 2010
Expires: Dec. 31, 2010
Awarded Amount to Date: $149,971
Principal Investigator: Eric Ervin
Sponsor: Electronic Bio Sciences

This Small Business Innovation Research Phase I project proposes to develop a new, robust nanopore platform for direct DNA sequencing. The stability of current nanopore sensor platforms has limited their potential. As such, a more robust nanopore is needed. During this project, the investigators aim to fabricate a highly-stable, reproducibly sized nanopore that is ideally suited for low-noise, high-bandwidth DNA sequencing applications. The improvement in robustness over current nanopore technology will allow examination of voltage regimes, which previously have not been able to be used in conjunction with nanopores. The commercial potential of this project is the fabrication of a low-cost, easy-to-use DNA sequencing system that provides highly accurate short reads.


The microbial response to the Deepwater Horizon oil spill

Start Date: July 1, 2010
Expires: June 30, 2011
Awarded Amount to Date: $199,953
Principal Investigators: Andreas Teske, Christopher Martens, Daniel Albert, Barbara MacGregor
Sponsor: University of North Carolina at Chapel Hill

This project will conduct a time series of microbiological and geochemical assessments of the consequences of the Deepwater Horizon oil spill offshore the Louisiana coast. The researchers are building on a large database of pre-spill baseline microbiology and biogeochemistry at a microbial observatory near the Deepwater Horizon site they have occupied since 2005. They are applying molecular, gene-based analyses of the microbial community structure and function in surface water and underlying sediments; in situ water column dissolved oxygen and light hydrocarbon measurements using advanced sensor technologies for deep water plume tracking; and a biogeochemical survey of the sediments and water in the immediate vicinity of and at increasing distance from the oil spill, and on different time scales during follow-up cruises. 16S rRNA and functional gene sequencing of total microbial DNA and RNA from contaminated and clean water and sediments will monitor how the oil-affected microbial community changes in composition and activity. High-throughput pyrosequencing of PCR-amplified rRNA fragments will increase the coverage by approximately three orders of magnitude, and allow for the detection of minority microbial populations that go unnoticed in conventional clone libraries. Special attention will be paid to the enrichment of oil-degrading bacteria in natural samples and in time-series experiments conducted in the lab, to monitor their growth with group-specific PCR, to monitor geochemical changes concomitant with the establishment and enrichment of a hydrocarbon-degrading microbial community, and to identify potential carbon incorporation pathways with stable isotope probing of nucleic acids. The results of this project will identify which bacterial and archaeal populations, and in which sequence, respond to oil spill events in marine sediments and the water column, and the attendant — often beneficial — biogeochemical consequences of this massive restructuring of the microbial community and their activities. Most importantly, this project will provide comprehensive microbial and geochemical coverage of different marine habitats on the geographical and time scale of the oil spill as it is unfolding, according to the grant abstract.


Harnessing Next-Generation Sequencing for Molecular Systematics

Start Date: June 1, 2010
Expires: May 31, 2012
Awarded Amount to Date: $13,223
Principal Investigators: Michael Sorenson, Jeffrey DaCosta
Sponsor: Trustees of Boston University

Phylogenetic trees are often based on just one or a few genetic loci, each representing a very small portion of the full genetic complement of a species. These small samples may produce misleading results due to complications arising from processes such as random genetic drift, natural selection, and hybridization. For some time, it has been recognized that the ideal solution would be to construct phylogenies using a large number of genetic loci sampled throughout the genome, but the cost of this approach has been prohibitive. Using two groups of bird species with different modes of reproduction and rates of speciation, this research will test the efficacy of an unspecified next-generation sequencing method as a low-cost solution for recovering and sequencing essentially the same set of thousands of genetic loci from related species.

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Towards rapid sequencing of individual DNA molecules in graphene nanogaps

Start Date: June 1, 2010
Expires: May 31, 2012
Awarded Amount to Date: $250,000
Principal Investigator: Hendrik Postma
Sponsor: The University Corporation, Northridge (California State University, Northridge)

This is an exploratory study to read the base sequence of a single DNA molecule using a graphene nanogap. Because graphene is a single atom thick, it is proposed that single- base resolution of the conductance can be readily obtained. Theoretical modeling shows that the expected sequencing error rate is 0 percent up to a nanogap width of 1.6 nanometers. The proposed work will demonstrate that the sequencing technology is technically feasible. It focuses on graphene nanogap fabrication, optimizing the graphene for applications in water, and demonstration of DNA translocating through the graphene nanogap. Successful completion will open a new research field in graphene-nanogap-based DNA sequencing. The expected ability to sequence large repeat-rich sections of DNA material will open up new windows on the study of the human genome, according to the researcher.


Platform, pipeline, and analytical tools for next-generation genotyping to serve breeding efforts in Africa

Start Date: April 1, 2010
Expires: March 31, 2011
Awarded Amount to Date: $671,035
Principal Investigators: Edward Buckler, Stephen Kresovich, Charles Tom Hash, Sharon Mitchell, Kassa Fentaye
Sponsor: Cornell University

This research effort aims to solve the technical problems associated with applying high-throughput high-density genotyping and developing an operational "model" for a wide range of crops. The project will exploit and optimize next-generation sequencing technologies as high-throughput genotyping assays for maize and sorghum varieties important to farmers in sub-Saharan Africa and other semi-arid, tropical regions of the world. Using next-generation sequencing technologies, combined with high levels of multiplexing and very inexpensive sample preparation methods, the project will establish a platform to provide 100,000 to 1 million markers per individual for a cost substantially below current field and laboratory costs. This platform will produce robust protocols for the entire pipeline, from DNA preparation to bioinformatic analyses, which are essential for genomic selection. Moreover, these approaches will be generalized, so in the future, any large number of individuals of any species can be genotyped with equal ease. Reducing the genotyping costs and increasing its applicability to all crops will enable plant breeders to employ genomic selection to facilitate crop improvement.


High-Quality Genome Sequences of Two Divergent Woolly Mammoths

Start Date: March 15, 2010
Expires: Feb. 28, 2011
Awarded Amount to Date: $300,000
Principal Investigators: Stephan Schuster, Webb Miller
Sponsor: Pennsylvania State University

A recent analysis of mitochondrial DNA sequences detected a deep split in the woolly mammoth population that has not been observed in the fossil record. Still more recently, a preliminary survey of the mammoth's full DNA complement suggested that the split can be observed in two particular specimens, called M4 and M25 for historical reasons. These observations, though quite limited and preliminary, lead to the hypotheses that the woolly mammoth clades exemplified by M4 and M25 were genetically quite distinct, separating over a million years ago, and that M25 clade became extinct well before coming into contact with humans. The methods employed in this project will refine genomic sequencing and ultimately lead to a greater understanding of wooly mammoth genomic evolution over the last 100,000 years.


Rapid enrichment, sequencing, and assembly of targeted genomic DNA

Start Date: March 15, 2010
Expires: Feb. 28, 2011
Awarded Amount to Date: $102,930
Principal Investigator: Michael Axtell
Sponsor: Pennsylvania State University

A powerful method to identify important cis-regulatory elements is to align DNA sequences flanking transcribed genes from multiple, related species. A major technical bottleneck of this approach is determining the flanking DNA sequences themselves. This project seeks to develop a rapid and flexible method to quickly determine the DNA sequence surrounding a gene of interest in multiple species.

The Scan

US Booster Eligibility Decision

The US CDC director recommends that people at high risk of developing COVID-19 due to their jobs also be eligible for COVID-19 boosters, in addition to those 65 years old and older or with underlying medical conditions.

Arizona Bill Before Judge

The Arizona Daily Star reports that a judge weighing whether a new Arizona law restricting abortion due to genetic conditions is a ban or a restriction.

Additional Genes

Wales is rolling out new genetic testing service for cancer patients, according to BBC News.

Science Papers Examine State of Human Genomic Research, Single-Cell Protein Quantification

In Science this week: a number of editorials and policy reports discuss advances in human genomic research, and more.