Assistant Professor, Biology Department
Education and Training
B.S. in Biology, State University of New York College at Cortland
Ph.D. in Molecular Biology, Syracuse University
Postdoctoral Training: Wadsworth Center, Albany, NY
Tel: (518) 276-2166
Fax: (518) 276-2851
Office: Center for Biotechnology and Interdisciplinary Studies Rm. 2123
Lab: Center for Biotechnology and Interdisciplinary Studies Rm. 2332
Rensselaer Polytechnic Institute
110 8th Street
Troy, NY 12180-3590
Aging, Mechanisms and consequences of genome instability, Retrotransposons
We live everyday with the consequences of aging and can readily understand aging as a progressive process that affects life functions in humans and other organisms. Yet aging is challenging to understand from a scientific perspective. We do not know if aging has one or many underlying causes. Aging could be viewed as an intrinsic progressive decline in organismal function or as a collection of diseases/conditions that occur with increasing frequency over the lifespan of an organism. There are many hypotheses regarding the cause(s) of aging. One such hypothesis is that the accumulation of genetic damage limits lifespan. While mutations and genome rearrangements are known to occur with increased frequency during aging, a direct role for genetic damage in causing normal aging has yet to be demonstrated. The Maxwell lab is investigating the mechanisms underlying and the consequences of genome instability during aging. Current projects use Saccharomyces cerevisiae (budding yeast) as a model organism and focus on the potential contribution of mobile genetic elements known as retrotransposons to aging-associated increases in mutations and genome rearrangements.
Saccharomyces cerevisiae has proven to be a useful model organism for studying aging and retrotransposons. Retrotransposons are mobile DNA elements that comprise a large fraction of the sequences in the genomes of many organisms and that can cause mutations. These elements replicate (retrotranspose) by reverse transcribing RNA intermediates in a process that results in insertions of new copies of retrotransposon sequences at genomic sites. Retrotransposons have produced interesting phenotypic variations in a variety of organisms and have resulted in disease-causing mutations in humans. S. cerevisiae provides one of the few systems in which the mobility of endogenous retrotransposons can be easily quantified and manipulated. Also, genetic pathways and factors that regulate yeast aging influence aging in other organisms, including mammals. Some drugs that are being tested for anti-aging effects in humans were first identified through studies in yeast. The Maxwell lab is taking advantage of genetic systems and experimental tools available for yeast to examine the contribution of retrotransposition, as well as DNA replication and repair activities, to aging-associated increases in mutations and genome rearrangements. The main goals are to determine whether specific mechanisms, such as retrotransposition, could be targets for interventions to reduce genetic damage during aging and experimentally manipulated to further study the relationship between genome instability and lifespan. The results of these experiments will likely be relevant for understanding aging in many organisms.
A variety of genetic and molecular biology tools are used to pursue these studies, such as: introduction of multiple mutations to manipulate retrotransposition levels or DNA repair activities; use of alternative growth conditions to manipulate retrotransposition levels; genetic selection or screening systems to quantify mutation, chromosome rearrangement, and retrotransposition frequencies; DNA sequencing to characterize mutations and chromosome rearrangements; pulsed-field gel electrophoresis of intact yeast chromosomes to identify chromosome rearrangements; magnetic sorting of surface-labeled yeast cells to separate old mother and young daughter cells.
Maxwell, P. H., Burhans, W. C., and Curcio, M. J. (2011). Retrotransposition is associated with genome instability during chronological aging. Proc. Natl. Acad. Sci. USA 108(51):20376-20381. PMCID: PMC3251071
Stamenova, R., Maxwell, P. H., Kenny A. E., and Curcio, M. J. (2009). Rrm3 protects the genome from instability at nascent sites of retrotransposition. Genetics 182(3):711-723. PMCID: PMC2710153
Maxwell, P. H. and Curcio, M. J. (2008). Incorporation of Y’-Ty1 cDNA destabilizes telomeres in Saccharomyces cerevisiae telomerase-negative mutants. Genetics 179(4): 2313-2317. PMCID: PMC2516100
Maxwell, P. H., Belote, J. M., and Levis, R. W. (2008). Developmental and tissue-specific accumulation pattern for the Drosophila melanogaster TART ORF1 protein. Gene 415(1-2): 32-39.
Maxwell, P. H. and Curcio, M. J. (2007). Retrosequence formation restructures the yeast genome. Genes Dev. 21(24): 3308-3318. PMCID: PMC2113031
Maxwell, P. H. and Curcio, M. J. (2007). Host factors that control LTR-retrotransposons in Saccharomyces cerevisiae: implications for the regulation of mammalian retroviruses. Eukaryot. Cell 6(7): 1069-1080. PMCID: PMC1951103
Maxwell, P. H., Belote, J. M., and Levis, R. W. (2006). Identification of multiple transcription initiation, polyadenylation, and splice sites in the Drosophila melanogaster TART family of telomeric retrotransposons. Nucleic Acids Res. 34(19): 5498-5507. PMCID: PMC1636488
Maxwell, P. H., Coombes, C., Kenny, A. E., Lawler, J. F., Boeke, J. D., and Curcio, M. J. (2004). Ty1 mobilizes subtelomeric Y’ elements in telomerase-negative Saccharomyces cerevisiae survivors. Mol. Cell. Biol. 24(22): 9887-9898. PMCID: PMC525482