Computational Genomics Unit
Emmanouil "Manolis" Maragkakis, Ph.D.
Stadtman Investigator Head
Functional Epigenomics Unit
Laboratory of Genetics and Genomics
The Computational Genomics Unit, led by Dr. Maragkakis, focuses on understanding the high-dimensional regulation of gene expression as a key component of discovering the mechanistic basis of the physiology and diseases of aging. We employ experimental and computational approaches to discover fundamental biological mechanisms that control RNA stability and dynamics. We develop tools to integrate high-throughput short- and long-read sequencing and machine learning to decipher the defining features of co-translational mRNA decay, how it is regulated, and the downstream effects of RNA dynamics in aging organs, tissues, and cells.
Quantification of gene expression levels is perhaps one of the most fundamental assays in biology. Yet several studies have shown that measured RNA levels correlate poorly with endogenous protein levels. We recently discovered that endogenously generated mRNA fragments represent a sizable fraction of the total mRNA pool indicating that current methods are inherently inaccurate. The lab works to re-define the functional mRNA molecule and understand RNA decay and biological steps, endonucleolytic or exonucleolytic, that drive the decay process. We design new methods based on long-read sequencing to discover and quantify the subset of mRNA molecules in cells that can produce bona fide proteins and to understand cis- and trans-acting mRNA degradation determinants. We use computational tools to model the circuitry of RNA regulation and the crosstalk of co-translational decay with miRNAs and RNA-binding proteins. Ultimately, we seek to understand the effects of coding and non-coding polymorphisms in aging-associated diseases and to determine RNA dynamics across the aging process.
RNA dynamics and co-translational mRNA decay
Machine learning and computational modeling
Cedric Belair, RNA Biology Specialist
Ibrahim F*, Oppelt J*, Maragkakis M*, Mourelatos Z, Ribothrypsis, a novel process of canonical mRNA decay, mediates ribosome-phased mRNA endonucleolysis Nucleic Acids Res. gkab713. (2021). PMID: 34428294
Ibrahim F*, Maragkakis M*, Alexiou P, Mourelatos Z, Ribothrypsis, a novel process of canonical mRNA decay, mediates ribosome-phased mRNA endonucleolysis Nat. Struct. Mol. Biol. 25, 302–310 (2018). PMID: 29507394
Tadashi N, Maragkakis M, Amyotrophic Lateral Sclerosis associated FUS mutation shortens mitochondria and induces neurotoxicity, Scientific Reports, 8, 15575 (2018) PMID: 30349096
Maragkakis M*, Alexiou P*, Nakaya T, Mourelatos Z, CLIPSeqTools - A novel bioinformatics CLIP-Seq analysis suite. RNA 22, 1–9 (2016). PMID: 26577377
Vourekas A*, Alexiou P*, Vrettos N, Maragkakis M, Mourelatos Z, Sequence-dependent but not sequence-specific piRNA adhesion traps mRNAs to the germ plasm. Nature 531, 390–394 (2016). PMID: 26950602
Vourekas A*, Zheng K*, Fu Q*, Maragkakis M*, Alexiou P, Pillai RS, Mourelatos Z, Wang PJ, The RNA helicase MOV10L1 binds piRNA precursors to initiate piRNA processing. Genes Dev. 29, 617–629 (2015). PMID: 25762440
Maragkakis M, Reczko M, Simossis VA, Alexiou P, Papadopoulos GL, Dalamagas T, Giannopoulos G, Goumas G, Koukis E, Kourtis K, Vergoulis T, Koziris N, Sellis T, Tsanakas P, Hatzigeorgiou AG, DIANA-microT web server: elucidating miRNA functions through target prediction. Nucleic Acids Res. 37, W273–6 (2009). PMID: 19406924