Jake Jacobs received his BS in Biological Sciences with a concentration in Microbiology in 2008 from Cornell University. At Cornell, Jake’s interest in Biology began with an interest in parasitic organisms, and he pursued this interest in the laboratory of Dr. Dwight Bowman, where he studied physical treatments that reduce the infectivity of Ascarissuum eggs in a mouse model. However, these early experiences in laboratory research were not rewarding enough for Jake to dedicate an entire life to parisitology research, so Jake pursued a Master’s degree in biology at New York University. At NYU, Jake worked as a research scientist in the laboratory of Dr. Patrick Eichenberger in the Center for Genomic and Systems Biology. It was in this setting that Jake’s true passion for bench research, i.e. microorganisms and basic biological and biotechnological research blossomed. His thesis at NYU investigated the development of the Bacillus subtilis spore coat, a model for the infectious agent anthrax. Specifically, he became interested in the mechanism behind how the complex spore coat, comprised of over >50 proteins, is faithfully assembled. Using a high-throughput screen, Jake was able to determine that physical interactions between several coat proteins drives major organizational patterns in the spore coat. Also at NYU, while Jake’s passion for bench research was developing, he started to develop a passion for teaching and mentoring. In addition to his own project, he developed and supervised the projects of several undergraduate, high school, and master’s students working in Dr. Eichenberger’s lab, served as a teaching assistant for an introductory biology course for undergraduates, and independently tutored students in biology, chemistry, and mathematics.

Jake’s success at NYU led him to pursue a PhD at Rutgers University in the Molecular Biosciences and Biotechnology. Upon acceptance, Jake’s strong academic track record allowed him to be selected as a UMDNJ Foundation Research Scholar. Because of Rutgers’ breadth of quality research available, he decided to pursue what he calls the “central dogma rotation plan,” pursuing a rotation in DNA replication, transcription, and translation. First, to fulfill the translation aspect, Jake worked in Dr. Paul Copeland’s lab on selenocysteine incorporation, where he gained experience in protein methodologies like purification, immunoprecpitation, and Western blotting. Next, he moved the study of DNA replication in the laboratory of Dr. Steven Brill, where he learned a great deal about the power of genetic screens in yeast, biochemistry, and also established insect cell culture and baculovirus purification protocols for the purification of a protein too large to purify in bacteria or yeast. Lastly, in fulfillment of the transcription aspect, he rotated with Dr. Mikel Zaratiegui, where he learned about the power of genomics and high-throughput sequencing. 

Jake’s rotation project with Dr. Zaratiegui eventually developed into what would eventually become his thesis proposal. Prior to Jake’s rotation, Dr. Zaratiegui found that a mobile genetic element, the fission yeast long terminal repeat (LTR) retrotransposon Tf1, integrates near the binding sites of a DNA binding protein called Sap1. Sap1 is a protein that acts to control the direction of DNA replication at several genomic loci, particularly in the promoters of genes, the rDNA repeats, and at retrotransposon LTR. Sap1 performs this action by causing polar replication fork blockage. Early on, working with high-throughput sequencing data, Jake realized that the binding strength of Sap1, as measured by ChIP-seq data, did not accurately predict the number of insertions a particular binding site received, suggesting additional factors guide Tf1 insertion. Using various transposon trapping strategies, including novel techniques he developed, he realized that the additional factor is Sap1’s ability to act as a replication fork barrier. This interesting discovery revealed a connection between retrotransposon integration and DNA replication. This surprising connection put the integration mechanisms of other studied retrotransposons in a new light. Many of these elements integrate into known fork barriers like tRNA and satellite repeats in heterochromatin, but these preferences were thought to mainly be because of interactions between host factors and the integrase, not features of the replication fork. Jake eventually was able to publish these novel findings in the highly prestigious journal Science. Jake has also presented these findings at talks at Cold Spring Harbor Laboratories and Keystone Symposia, and more recently, gave a poster presentation on these findings at the Woods Hole Marine Biological Laboratory.

In addition to his  main thesis project, Jake was also able to work on a number of side projects. During his second year, Jake developed a novel CRISPR/Cas9 platform for use in fission yeast. This was a particular challenge since the classic RNA Pol III promoters used to express the gRNA needed for CRISPR/Cas9 did not work in fission yeast, so Jake developed an expression scheme that depends on RNA Pol II. Jake eventually published the method in the journal Nature Communications. Fission yeast labs all over the world are currently using his expression platform. Jake is also involved in other projects in the lab, including studying links between mRNA processing and RNAi, the silencing of LTR retrotransposons in closely related species of fission yeast, and looking at ways to delete all the transposons in fission yeast to study their role in genome integrity, organization, and evolution. Further, Jake continues to hone his mentoring skills, and has trained two undergraduate students in advanced molecular biology techniques.

Aside from academic work, Jake also completed a 10-week summer internship at Celgene Cellular Therapeutics. At Celgene, he used his expertise on the development of CRISPR/Cas9 technologies to enhance key properties of cell-based therapies in development. While at Celgene, Jake also helped train the R&D department in the development, design, and delivery of CRISPR/Cas9 to primary cell culture, and helped carve out a path toward methods of characterizing off-target activity, and enhancing on-target activity through selection and increased delivery efficiency.

Jake strongly feels that the Rutgers Biotechnology Training program’s emphasis on personal skill development and academic and research excellence has helped fuel Jake’s success, and has set him up for a an exciting career in the biotechnology industry in the years to come.

Papers Published, In Press, or Submitted

Jacobs JZ, Rosado-Lugo JD, Cranz-Mileva S, Ciccaglione K, Tournier V, Zaratiegui M. “Arrested replication forks guide retrotransposon integration.” Science, 2015; 349: 1549-1553.

Jacobs JZ, Ciccaglione K, Tournier V, Zaratiegui M. Implementation of the CRISPR/Cas9 system in fission yeast. Nature Communications, 2014; 5: 5344.

Meeting Presentations

Retrotransposition guided into arrested replication forks.” (poster)Mobile Genetic Elements: In silico, In vitro, In vivo. September 3, 2015. Woods Hole, MA.

“Sap1 replication fork barrier activity guides the integration of LTR retrotransposons in Fission Yeast.” (oral) Keystone Mobile Genetic Elements and Genome Evolution Meeting. March 11, 2014. Sante Fe, NM.

“Sap1 guides the integration of LTR retrotransposons inSchizosaccharomyces pombe.” (oral) Mobile Genetic Elements Regional Meeting. October 25, 2013. Cold Spring Harbor, NY

Awards and Honors

UMDNJ Foundation of Research Scholars,  2011-14

Rutgers NIH Biotechnology Training Program Fellowship, 2011-13

Anne B. and James B. Leathem Fellow, 2013-14