Biological Sciences Building West
Biological Sciences Building West
Joined the Department in 1997
- BS, 1983 SUNY Albany Biology
- MS, 1987 SUNY Albany Molecular Biology
- PhD, 1991 SUNY Albany Molecular Biology
- Postdoctoral Research, Dartmouth Medical School, Biochemistry
Circadian Rhythms in the development of spores in the fungus Neurospora crassa
Current research in the Bell-Pedersen lab uses molecular, biochemical, genetic, and genomic tools to understand how circadian oscillators control rhythmic gene expression and protein production that are critical to critical to human health and drug metabolism. We are addressing a longstanding puzzle – the existence of proteins that show robust circadian rhythms in their levels despite no rhythm in the levels of the corresponding mRNAs. We discovered that most of this regulation is due to clock control of mRNA translation. We showed that the clock in Neurospora crassa regulates daily rhythms in the activity of the conserved translation initiation factor eIF2a and elongation factor eEF2 that accounts for more than half of rhythmic translation. We also discovered a novel mechanism for rhythmic mRNA translation that involves clock control of ribosome composition and function. In addition, while it was thought that cells always maintain the highest possible translation fidelity, we found that stop codon readthrough, and thus translation fidelity, is clock-controlled, and that this depends on the composition of the ribosome. We also found that the clock controls the levels of tRNA synthetases that are critical to translation and translation fidelity. Importantly, aging is associated with both reduced circadian rhythm amplitude and decreased translation fidelity. An exciting outcome of this work is the potential that increasing circadian amplitude could improve translation fidelity and slow down the aging process.
- Castillo, KD, Wu, C, Ding, Z, Lopez-Garcia, OK, Rowlinson, E, Sachs, MS et al.. A circadian clock translational control mechanism targets specific mRNAs to cytoplasmic messenger ribonucleoprotein granules. Cell Rep. 2022;41 (13):111879. doi: 10.1016/j.celrep.2022.111879. PubMed PMID:36577368 .
- Maity, AK, Lee, SC, Hu, L, Bell-Pedersen, D, Mallick, BK, Sarkar, TR et al.. Circadian Gene Selection for Time-to-event Phenotype by Integrating CNV and RNAseq Data. Chemometr Intell Lab Syst. 2021;212 :. doi: 10.1016/j.chemolab.2021.104276. PubMed PMID:35068632 PubMed Central PMC8775911.
- Shen, L, Su, Z, Yang, K, Wu, C, Becker, T, Bell-Pedersen, D et al.. Structure of the translating Neurospora ribosome arrested by cycloheximide. Proc Natl Acad Sci U S A. 2021;118 (48):. doi: 10.1073/pnas.2111862118. PubMed PMID:34815343 PubMed Central PMC8640747.
- Ding, Z, Lamb, TM, Boukhris, A, Porter, R, Bell-Pedersen, D. Circadian Clock Control of Translation Initiation Factor eIF2α Activity Requires eIF2γ-Dependent Recruitment of Rhythmic PPP-1 Phosphatase in Neurospora crassa. mBio. 2021;12 (3):. doi: 10.1128/mBio.00871-21. PubMed PMID:34006661 PubMed Central PMC8262944.
- Alder-Rangel, A, Idnurm, A, Brand, AC, Brown, AJP, Gorbushina, A, Kelliher, CM et al.. The Third International Symposium on Fungal Stress - ISFUS. Fungal Biol. 2020;124 (5):235-252. doi: 10.1016/j.funbio.2020.02.007. PubMed PMID:32389286 PubMed Central PMC7438019.
- Karki, S, Castillo, K, Ding, Z, Kerr, O, Lamb, TM, Wu, C et al.. Circadian clock control of eIF2α phosphorylation is necessary for rhythmic translation initiation. Proc Natl Acad Sci U S A. 2020;117 (20):10935-10945. doi: 10.1073/pnas.1918459117. PubMed PMID:32355000 PubMed Central PMC7245112.
- Baek, M, Virgilio, S, Lamb, TM, Ibarra, O, Andrade, JM, Gonçalves, RD et al.. Circadian clock regulation of the glycogen synthase (gsn) gene by WCC is critical for rhythmic glycogen metabolism in Neurospora crassa. Proc Natl Acad Sci U S A. 2019;116 (21):10435-10440. doi: 10.1073/pnas.1815360116. PubMed PMID:31048503 PubMed Central PMC6534987.
- Goldsmith, CS, Kim, SM, Karunarathna, N, Neuendorff, N, Toussaint, LG, Earnest, DJ et al.. Correction to: inhibition of p38 MAPK activity leads to cell type-specific effects on the molecular circadian clock and time-dependent reduction of glioma cell invasiveness. BMC Cancer. 2019;19 (1):101. doi: 10.1186/s12885-018-5238-0. PubMed PMID:30674294 PubMed Central PMC6344983.
- Goldsmith, CS, Kim, SM, Karunarathna, N, Neuendorff, N, Toussaint, LG, Earnest, DJ et al.. Inhibition of p38 MAPK activity leads to cell type-specific effects on the molecular circadian clock and time-dependent reduction of glioma cell invasiveness. BMC Cancer. 2018;18 (1):43. doi: 10.1186/s12885-017-3896-y. PubMed PMID:29316898 PubMed Central PMC5761097.
- Wu, C, Dasgupta, A, Shen, L, Bell-Pedersen, D, Sachs, MS. The cell free protein synthesis system from the model filamentous fungus Neurospora crassa. Methods. 2018;137 :11-19. doi: 10.1016/j.ymeth.2017.12.003. PubMed PMID:29294368 PubMed Central PMC6047757.