loldfield

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Bio

Lauren Oldfield, PhD is an assistant professor at the J. Craig Venter Institute in the Synthetic Biology and Bioenergy department. Her diverse research interests include viral synthetic genomics for large DNA viruses and investigating the role of the microbiome in injury after pollution exposure.

In her postdoctoral research at the JCVI, she worked with Dr. Sanjay Vashee to develop synthetic genomics tools to improve researchers’ ability to manipulate herpesviruses. Through a strong collaboration with Dr. Prashant Desai, an expert in herpes simplex virus type 1 (HSV-1) biology, at Johns Hopkins University, both groups worked together to successfully implement a novel synthetic genomics method to clone and assemble the HSV-1 genome from smaller overlapping genomic fragments and reconstitute infectious virus in tissue culture. By cloning the HSV-1 genome in fragments, the team can rapidly engineer changes to these fragments in parallel and reassemble full length genomes with a combination of mutant and wild-type parts.

Dr. Oldfield is now working to expand these synthetic genomics tools to additional viruses and to new scientific and medical problems. For example, this system can be used to study the biology of the inverted repeat regions of HSV-1 and determine if they influence virulence. HSV-1 is also used as an oncolytic virus and gene therapy vector and these tools will enable rapid engineering of HSV-1 based therapeutics. Drs. Vashee and Oldfield also are working to expand this system to other herpesviruses, inlcuding Epstein-Barr virus with Dr. Desai and human cytomegalovirus with Dr. Klaus Früh at Oregon Health and Science University, and to viruses that are important agricultural pathogens.

Dr. Oldfield is also a fellow in the Emerging Leaders in Biosecurity Initiative, which aims to provide education and networking to scientists and policy experts from academia, industry, nonprofits and government on issues of biosecurity.

Ongoing pilot projects with Dr. Kymberly Gowdy at East Carolina University and Dr. Alexey Fedulov will investigate the effects of ozone and particulate matter, respectively, on the microbiome in mouse model systems. Understanding the contribution of the microbiome may lead to diagnostics or treatments to help mitigate the effects of pollution exposure.

She was also involved in other virus projects at JCVI studying Zika virus, rhinovirus, and enterovirus D68 and initiatives to look at the viral component of the microbiome and its contributions to cancer. As a graduate student under the direction of Dr. Graham Hatfull, a world renown bacteriophage expert, Dr. Oldfield studied several aspects of bacteriophage gene expression using RNA-Seq, promoter assays and characterizing the genetic switch for lytic versus lysogenic growth.

Research Priorities

Characterize and assess the phenotype of regions of repeated sequence in HSV-1

  • Determine the accurate sequence of the inverted structural repeats and smaller variable number tandem repeats of HSV-1
  • Isolate clones of these regions and assemble HSV-1 genomes with variants of the repeats

Understanding the role of the microbiome, including the resident virome, in the initiation and progression of cancer

  • Focus on the molecular mechanisms of herpesvirus oncogenesis

Bacteriophage-based diagnostics for antimicrobial resistance

  • Develop synthetic genomics assembly tools to rapidly manipulate bacteriophage genomes
  • Improve existing diagnostic phage to sensitively detect bacteria

Utilizing genomics to better understand viral outbreaks

  • Currently working with Zika virus and enterovirus D68

Projects

Select Publications

Genome-wide engineering of an infectious clone of herpes simplex virus type 1 using synthetic genomics assembly methods.
Proceedings of the National Academy of Sciences of the United States of America. 2017-09-19; 114.38:
PMID: 28928148
Efficient size-independent chromosome delivery from yeast to cultured cell lines.
Nucleic acids research. 2017-04-20; 45.7: e50.
PMID: 27980064
The Human Microbiome and Cancer.
Cancer prevention research (Philadelphia, Pa.). 2017-04-01; 10.4: 226-234.
PMID: 28096237
An Unusual Phage Repressor Encoded by Mycobacteriophage BPs.
PloS one. 2015-01-01; 10.3: e0137187.
PMID: 26332854
Mutational analysis of the mycobacteriophage BPs promoter PR reveals context-dependent sequences for mycobacterial gene expression.
Journal of bacteriology. 2014-10-01; 196.20: 3589-97.
PMID: 25092027
Integration-dependent bacteriophage immunity provides insights into the evolution of genetic switches.
Molecular cell. 2013-01-24; 49.2: 237-48.
PMID: 23246436
BRED: a simple and powerful tool for constructing mutant and recombinant bacteriophage genomes.
PloS one. 2008-01-01; 3.12: e3957.
PMID: 19088849