Lauren M. Oldfield, PhD

Staff Scientist


301-795-7653

Bio

I am a Staff Scientist at the J. Craig Venter Institute in the Synthetic Biology and Bioenergy department. I am currently interested in viral diversity and viral synthetic genomics. I am especially focused on using the synthetic genomics tools we have developed for herpesviruses to investigate the role of repeated sequences in herpes simplex virus type 1 (HSV-1). In my postdoctoral research at the JCVI, I worked with Dr. Sanjay Vashee to develop synthetic biology tools to improve our ability to manipulate herpesviruses. We have developed a strong collaboration with Dr. Prashant Desai, an expert in HSV-1 biology, at Johns Hopkins University. Both groups worked together to successfully implement a novel synthetic genomics method to assemble the HSV-1 genome from smaller overlapping genomic fragments and reconstitute infectious virus in tissue culture. By cloning the HSV-1 genome as smaller fragments, we are able to rapidly engineer changes to these fragments in parallel and reassemble full length genomes with a combination of mutant and wild-type parts.

We also have funding for and are working to expand this system to Epstein-Barr virus with Dr. Desai and human cytomegalovirus with Dr. Klaus Früh at Oregon Health and Science University. The system will also be applicable to many large dsDNA viruses, such as herpesviruses and poxviruses, and will help to answer questions of basic biology, as well as to engineer and design of new therapeutics based on viral vectors. As a staff scientist, I have taken a leadership role in using synthetic biology and sequencing to evaluate challenging aspects of herpesvirus biology. I am also involved in other viral 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, I worked on several aspects of bacteriophage gene expression using RNAseq, 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
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; 10.9: 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