- Fungal and yeast genetics research
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Microbial Metabolic Engineering and Bioproduction
- Bioinformatics and Genomic Networks
- RNA modifications and cancer
- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- Machine Learning in Bioinformatics
- Gene Regulatory Network Analysis
- Gene expression and cancer classification
- DNA Repair Mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Mitochondrial Function and Pathology
- Monoclonal and Polyclonal Antibodies Research
- DNA and Nucleic Acid Chemistry
- Polyamine Metabolism and Applications
- Cellular transport and secretion
- Genetic Neurodegenerative Diseases
- Endoplasmic Reticulum Stress and Disease
- Folate and B Vitamins Research
- Advanced biosensing and bioanalysis techniques
- Ubiquitin and proteasome pathways
- Lipid metabolism and biosynthesis
- Genomics, phytochemicals, and oxidative stress
Texas A&M University
2015-2025
Center for Advancing Health
2024
Mitchell Institute
2004-2024
College Station Medical Center
2012-2024
National Institute of Diabetes and Digestive and Kidney Diseases
2008
Tufts University
1993-2003
Institute of Molecular Biology and Biophysics
2003
Massachusetts General Hospital
1996-1999
Harvard University
1997-1999
The eukaryotic cell cycle is driven by a cascade of cyclins and kinase partners including the G 1 cyclin Cln3p in yeast. As first step this cascade, uniquely positioned to determine critical growth-rate threshold for division. To analyze factors regulating CLN3 expression, we identified short upstream open reading frame (uORF) 5′ leader mRNA as translational control element. This element growth-dependent regulation synthesis because it specifically represses expression during conditions...
The mRNA cap-binding protein (eukaryotic initiation factor 4E [eIF4E]) binds the m7 GpppN cap on mRNA, thereby initiating translation. eIF4E is essential and rate limiting for synthesis. Overexpression of transforms cells, mutations in arrest cells G, cdc33 mutants. In this work, we identified promoter region gene encoding eIF4E, because previously as a potential myc-regulated gene. support our previous data, minimal, functional, 403-nucleotide was found to contain CACGTG E box repeats, core...
The common non-steroidal anti-inflammatory drug ibuprofen has been associated with a reduced risk of some age-related pathologies. However, general pro-longevity role for and its mechanistic basis remains unclear. Here we show that increased the lifespan Saccharomyces cerevisiae, Caenorhabditis elegans Drosophila melanogaster, indicative conserved eukaryotic longevity effects. Studies in yeast indicate destabilizes Tat2p permease inhibits tryptophan uptake. Loss replicative (RLS), but did...
Caloric restriction (CR) is known to extend life span across species; however, the molecular mechanisms are not well understood. We investigate mechanism by which glucose (GR) extends yeast replicative span, combining ribosome profiling and RNA-seq with microfluidic-based single-cell analysis. discovered a cross-talk between sensing regulation of intracellular methionine: GR down-regulated transcription translation methionine biosynthetic enzymes transporters, leading decreased...
Upstream events that trigger initiation of cell division, at a point called START in yeast, determine the overall rates proliferation. The identity and complete sequence those remain unknown. Previous studies relied mainly on size changes to identify systematically genes required for timely completion START. Here, we evaluated panels non-essential single gene deletion strains altered DNA content by flow cytometry. This analysis revealed most deletions cycle progression did not change size....
In several systems, including budding yeast, cell cycle-dependent changes in the transcriptome are well studied. contrast, few studies queried proteome during division. There is also little information about dynamic metabolites and lipids cycle. Here, authors present such for dividing yeast cells.
A long-standing problem is how cells that lack one of the highly similar ribosomal proteins (RPs) often display distinct phenotypes. Yeast and other organisms live longer when they specific proteins, especially large 60S subunit ribosome. However, longevity neither associated with generation time RP deletion mutants nor bulk inhibition protein synthesis. Here, we queried actively dividing through cell cycle. Our data link transcriptional, translational, metabolic changes to phenotypes loss...
Most cells must grow before they can divide, but it is not known how determine when have grown enough so commit to a new round of cell division. Several parameters affect the timing initiation division: size at birth, reach division, and fast that size. We report Saccharomyces cerevisiae mutants in metabolic biosynthetic pathways differ these variables, controlling division various ways. Some rate increase size, or any combination above. Furthermore, we show adenylate kinase, encoded by...
Amino acid starvation activates the protein kinase Gcn2p, leading to changes in gene expression and translation. Gcn2p is activated by deacylated tRNA, which accumulates when tRNA aminoacylation limited lack of substrates or inhibition synthesis. Pairing amino acids tRNAs catalyzed aminoacyl-tRNA synthetases, use quality control pathways maintain substrate specificity. Phenylalanyl-tRNA synthetase (PheRS) maintains specificity via an editing pathway that targets non-cognate Tyr-tRNAPhe....
Effective dietary strategies and interventions for monitoring exposures require accurate noninvasive methods to understand how diet modulates health risk of obesity; advances in technology are transforming the landscape enabling more specific tailored approaches nutritional guidance. This study explores use Raman spectroscopy (RS), a nondestructive analytical technique, identify changes mice skin response constant exposures. We found that RS is highly determine body composition as result...
A plasmid vector was constructed for the expression of a single chain Fv domain mouse mAb to Z-DNA (antibody Z22), which is encoded by VH10 and V kappa 10 gene family members along with Dsp2, JH4, J 4 segments. The coded PhoA secretion signal, VH segment, flexible peptide linker, VL (His)5, protein domain. Unique restriction sites allowed exchange segments as cassettes. Bacteria transformed secreted soluble recombinant specific Z-DNA-binding activity. When L Z22 replaced library splenic cDNA...
Coordination between cellular metabolism and DNA replication determines when cells initiate division. It has been assumed that only plays a permissive role in cell While blocking arrests division, it is not known whether an up-regulation of metabolic reactions accelerates cycle transitions. Here, we show increasing the amount mitochondrial overall proliferation promotes nuclear replication, nutrient-dependent manner. The Sir2p NAD+-dependent de-acetylase antagonizes this role. We found with...
The heavy (H) and light (L) chain V domains of anti-Z-DNA mouse mAb Z22 were expressed separately in bacteria. When mixed vitro, the associated stoichiometrically to reconstitute Ag binding site Z22, as judged by specific reactivity with Z-DNA anti-Z22 ld Abs. apparent Kd VH-VL association was 5.47 x 10(-8) M, measured surface plasmon resonance. A replacement at VL position 96, which reduced affinity a single Fv (clone LZ1-2) two orders magnitude, did not reduce interaction between VH...
How proliferating cells maintain the copy number and overall size of their organelles is not clear. We had previously reported that in budding yeast Saccharomyces cerevisiae G1 cyclin Cln3p required for vacuolar (lysosomal) homotypic fusion loss leads to fragmentation. The Cdc42p GTPase also vacuole fusion. Here we show scaffold protein Bem1p, a critical regulator activity, downstream effector cyclin-dependent kinase (Cdk) Cdc28p. Our results suggest Bem1p phosphorylated Cdk-dependent manner...
Background The unfolded protein response (UPR) is a eukaryotic signaling pathway, from the endoplasmic reticulum (ER) to nucleus. Protein misfolding in ER triggers UPR. Accumulating evidence links UPR diverse aspects of cellular homeostasis. responds overall synthesis capacity and metabolic fluxes cell. Because coupling metabolism with cell division governs when cells start dividing, here we examined role timing initiation cycle progression, yeast Saccharomyces cerevisiae....