Department of Biology
Loyola University Maryland
4501 North Charles Street
Baltimore, MD 21210-2699
Office: DS 374
Office tel: 410-617-2316
Areas of Interest: Molecular Biology and Genomics
Transposons are mobile DNA sequences that replicate and insert into new locations in the genome. Despite the fact that transposons can accumulate to very high levels (in fact, they comprise ~40% of the human genome), they are frequently referred to as “junk DNA” or “selfish DNA”. However, the presence of transposons dramatically affects genome stability since they are sites at which DNA sequences can pair and exchange genetic information. In cells with many copies of these repeated sequences, the chromosomes can mispair and improperly recombine, leading to chromosome rearrangements. These structural alterations can profoundly disturb the expression of genes on the affected chromosomes; indeed aberrant chromosomes are frequently present in cancerous cells. The tranposons that I study are the Ty1 elements of yeast, which are frequently associated with sites of chromosomal duplications, deletions and translocations. Yet, the overall incidence of these chromosome changes is rare, suggesting that the cell contains a mechanism to restrain improper pairing and recombination of DNA between the dispersed repeats. To identify those cellular factors that prevent tranposons from causing improper rearrangement of DNA, we use genetic screens. We hope to identify genes that, when deleted, increase the number of chromosome rearrangements in yeast strains with high numbers of transposons. These studies should provide important insights on how chromosome aberrations are prevented so that genetic information can be faithfully transmitted. In addition, we are studying whether chromosomal changes produced by transposon sequences can be advantageous to the cell by enabling evolution. We use a continuous culture system to evolve yeast strains in which we have manipulated the number and position of transposon sequences in the genome. Following experimental evolution, we use genomic technologies to measure fitness and monitor chromosome structure in the evolved strains so that we may learn whether repeated sequences provide a source of genetic variation that promotes genome evolution.
Retrotransposon overdose and genome integrity. Scheifele LZ, Cost GJ, Zupancic ML, Caputo EM, Boeke JD. Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13927-32.
Transposon insertion site profiling chip (TIP-chip).Wheelan SJ, Scheifele LZ, Martínez-Murillo F, Irizarry RA, Boeke JD. Proc Natl Acad Sci U S A. 2006 Nov 21; 103(47): 17632-7.
Teaching synthetic biology, bioinformatics and engineering to undergraduates: the interdisciplinary Build-a-Genome course. Dymond JS, Scheifele LZ, Richardson S, Lee P, Chandrasegaran S, Bader JS, Boeke JD. Genetics. 2009 Jan;181(1):13-21.
CLONEQC: lightweight sequence verification for synthetic biology. Lee PA, Dymond JS, Scheifele LZ, Richardson SM, Foelber KJ, Boeke JD, Bader JS. Nucleic Acids Res. 2010 May;38(8):2617-23.
Total Synthesis of a Functional Designer Eukaryotic Chromosome. Annaluru N, Muller H, Mitchell LA, Ramalingam S, Stracquadanio G, Richardson SM, Dymond JS, Scheifele LZ, Cooper EM, Cai Y, Zeller K, et al. Science. 2014; 344(6179):55-8.