Article
Biochemistry & Molecular Biology
Benjamin R. Harrison, Jessica M. Hoffman, Ariana Samuelson, Daniel Raftery, Daniel E. L. Promislow
Summary: Comparative phylogenetic studies have shed light on the evolution of metabolites across 50 million years in the genus Drosophila, revealing the conserved effects of sex and age on the metabolome. Modules in the metabolome show evidence of coevolution, enriched for specific biochemical pathways, and potentially influenced by functional relationships. These coevolutionary patterns differ between sexes and are affected by age, with some modules associated with lifespan variation, particularly in older flies, suggesting a role of metabolic associations in lifespan evolution over millions of years.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Article
Biotechnology & Applied Microbiology
Alexander Nash, Paolo Capriotti, Astrid Hoermann, Phillipos Aris Papathanos, Nikolai Windbichler
Summary: The research team explored the minimal genetic components needed to constitute autonomous gene drives in fruit flies, and designed the rcd-1r(d) allele which supports efficient gene drive. Such simple integral gene drives could enable the modularization of drive and effector functions.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Cell Biology
Xiaqing Zhao, Forrest T. Golic, Benjamin R. Harrison, Meghna Manoj, Elise Hoffman, Neta Simon, Richard Johnson, Michael J. MacCoss, Lauren M. McIntyre, Daniel E. L. Promislow
Summary: Activity levels and metabolome-wide profiles are strongly associated with age, and many individual metabolites show a strong association with lifespan. The metabolome provides a biological clock that predicts not only sample age but also future mortality rates and lifespan.
Article
Biology
Chiara Auwerx, Marie C. Sadler, Tristan Woh, Alexandre Reymond, Zoltan Kutalik, Eleonora Porcu, Evan Graehl Williams
Summary: We developed a multi-omics Mendelian randomization framework to study the causal role of metabolites in mediating the effect of gene expression on complex traits. Through this approach, we identified 216 transcript-metabolite-trait causal triplets involving 26 medically relevant phenotypes, with 58% of these associations missed by classical transcriptome-wide MR. Our simulation analyses show that our multi-omics MR framework outperforms classical MR approaches designed to detect causal relationships between single molecular traits and complex phenotypes, especially in the case of mediated effects.
Article
Neurosciences
Carlo N. G. Giachello, Iain Hunter, Tom Pettini, Bramwell Coulson, Athene Knufer, Sebastian Cachero, Michael Winding, Aref Arzan Zarin, Hiroshi Kohsaka, Yuen Ngan Fan, Akinao Nose, Matthias Landgraf, Richard A. Baines
Summary: The Drosophila connectome project aims to map the synaptic connectivity of the fly neural networks in order to better understand their development and function. Although impressive progress has been made in reconstructing specific synapses using electron microscopy data, the data are still underutilized. This study combines patch-clamp recordings with optogenetic stimulation to test the proposed synaptic connectivity in fruit fly larvae and highlights the need for functional validation and appropriate genetic tools in connectome projects.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biology
Stella Reichling, Peter F. Doubleday, Tomas Germade, Ariane Bergmann, Robbie Loewith, Uwe Sauer, Duncan Holbrook-Smith
Summary: Although the yeast Saccharomyces cerevisiae's genetic code has been sequenced for 25 years, the understanding of gene functions within it is still incomplete. High-throughput metabolomics provides a cost-effective and robust approach to uncovering gene function. The study used mass spectrometry to dynamically profile the metabolome of TOR and receptor genes mutants under rapamycin treatment, generating a dataset of over 7000 metabolomics measurements. The results demonstrate the efficacy of this approach in identifying novel potential TOR signaling-related genes and highlight the utility of dynamic perturbations for functional metabolomics.
Article
Urology & Nephrology
Bridget M. Lin, Ying Zhang, Bing Yu, Eric Boerwinkle, Bharat Thygarajan, Milagros Yunes, Martha L. Daviglus, Qibin Qi, Robert Kaplan, James Lash, Jianwen Cai, Tamar Sofer, Nora Franceschini
Summary: This study aimed to identify the source of variability in the association of metabolites with estimated glomerular filtration rate (eGFR) in Hispanics/Latinos with low chronic kidney disease prevalence. The results suggest that complex mechanisms contribute to the association of eGFR with metabolites and provide new insights into these associations.
KIDNEY INTERNATIONAL
(2022)
Article
Biochemistry & Molecular Biology
Carlos Lopez-Ortiz, Mary Edwards, Purushothaman Natarajan, Armando Pacheco-Valenciana, Padma Nimmakayala, Donald A. Adjeroh, Cristian Sirbu, Umesh K. Reddy
Summary: This study analyzed the transcriptomic and metabolomic responses of Drosophila flies fed a habanero pepper diet, identifying differentially expressed genes and accumulated metabolites. The findings revealed the impact of the pepper diet on olfactory sensitivity, behavioral responses, and metabolic pathways. This research is important for exploring the molecular mechanisms of pepper consumption.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Zhenhuang Zhuang, Xue Dong, Jinzhu Jia, Zhonghua Liu, Tao Huang, Lu Qi
Summary: This study found that a healthy sleep pattern is associated with a lower risk of type 2 diabetes mellitus (T2DM). They constructed a metabolomic signature consisting of 153 metabolites, which was strongly correlated with sleep pattern and inversely associated with T2DM risk. Mendelian randomization analysis further indicated a causal relationship between the metabolomic signature and incident T2DM.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Andrea Tapia, Martina Palomino-Schaetzlein, Marta Roca, Agustin Lahoz, Antonio Pineda-Lucena, Victor Lopez del Amo, Maximo Ibo Galindo
Summary: The study revealed that mild mitochondrial muscle disturbance plays an important role in Drosophila fitness, showing that down-regulation of Marf and Opa1 in muscle can have systemic effects on metabolism, particularly affecting metabolites involved in energetic homeostasis. The results suggest that these differences are more evident in younger flies, implying the presence of anticipative adaptions mediating protective changes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Rebecca A. A. MacPherson, Vijay Shankar, Lakshmi T. T. Sunkara, Rachel C. C. Hannah, Marion R. R. Campbell III, Robert R. H. Anholt, Trudy F. C. Mackay
Summary: Uhg4 is a critical lncRNA for reproduction in fruit flies, with pleiotropic effects on various fitness traits. Deletion mutants of Uhg4 showed delayed development, decreased viability, changes in sleep, responses to stress, and altered expression of co-regulated genes and genetic interaction networks associated with Uhg4. Gene ontology analyses revealed a wide range of biological processes influenced by Uhg4, including regulation of transcription and translation, morphogenesis, and stress response.
Review
Biochemical Research Methods
Koki Hayashi, Saleh Alseekh, Alisdair R. Fernie
Summary: Plant metabolites are primarily produced through enzymatic reactions encoded by genes in the genome. Mutations in enzyme-encoding or transcription factor-encoding genes can alter the metabolome by affecting enzyme activity or abundance. Insertion of transposable elements into non-coding regions can also impact transcription and metabolite content. Epigenetic variations, both transgenerational and non-transgenerational, have been found to control metabolism by regulating gene transcription. However, the role of epigenetics in metabolic control has been relatively understudied.
Review
Biochemistry & Molecular Biology
Abdelrahman AlOkda, Jeremy M. Van Raamsdonk
Summary: Thioredoxin and thioredoxin reductase are antioxidant enzymes that protect organisms from oxidative stress and play roles in cellular signaling and chaperone functions. Disruption or increased expression of these proteins can affect longevity in various model organisms, indicating their importance in determining lifespan. Additionally, a genetic variant of thioredoxin reductase has been associated with human lifespan. Overall, both cytoplasmic and mitochondrial thioredoxin systems are crucial for longevity.
Article
Biochemistry & Molecular Biology
Robert Kofler, Viola Nolte, Christian Schlotterer
Summary: The dynamics of transposable element invasions are influenced by multiple factors, and the transposition rate is only one of them. By studying the temperature-dependent activity of the P-element, researchers found that despite differences in transposition rates, the copy numbers of the P-element were very similar at different temperatures. The decrease in insertion rate as the copy number approached a plateau was accompanied by the production of piRNAs. However, fewer P-element insertions were observed in piRNA clusters than expected, indicating that factors other than the trap model influenced the dynamics of TE invasions.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Article
Biology
Katja Birker, Shuchao Ge, Natalie J. Kirkland, Jeanne L. Theis, James Marchant, Zachary C. Fogarty, Maria A. Missinato, Sreehari Kalvakuri, Paul Grossfeld, Adam J. Engler, Karen Ocorr, Timothy J. Nelson, Alexandre R. Colas, Timothy M. Olson, Georg Vogler, Rolf Bodmer
Summary: Researchers conducted whole genome sequencing on HLHS patients and their parents, identifying candidate genes related to the disease. Functional testing in a fruit fly heart model revealed the involvement of genes related to mitochondrial morphology and energy production. Additionally, the study suggests an oligogenic basis for HLHS, with the potential involvement of multiple genes and pathways. Further research on these candidate genes and their interactions can contribute to a better understanding of HLHS and other congenital heart diseases.