Light Microscopy core for NIDDK

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Abstract

The mission of the National Institutes of Health (NIH) is to seek fundamental knowledge about the nature and behavior of living systems and to apply that knowledge to enhance health, lengthen life, and reduce illness and disability. As part of the NIH, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Intramural Research Program (IRP) conducts biomedical research and training related to diabetes mellitus; endocrine, bone, and metabolic diseases; digestive diseases, including liver diseases and nutritional disorders; and kidney, urologic, and hematologic diseases. Intramural research is conducted in the Institute's laboratories and clinical facilities in Bethesda, Maryland and in Phoenix, Arizona. There are currently 18 Laboratories and Branches (i.e. 18 departments with different focus areas) in the NIDDK IRP (https://www.niddk.nih.gov/research-funding/at-niddk/labs-branches). Most if not all of these areas of research, either occasionally or on an ongoing basis, require light microscopy (LM) methods to qualitatively complement other assays, or as the basis of a quantitative assay. There are three main categories of LM. Conventional widefield, transmitted light techniques, such as darkfield or differential interference contrast (DIC), are still useful because of their innate ability to show cellular morphology. Second, an old standby, immunohistochemistry (IHC)-- using absorptive probes to colorize tissue in transmitted light-- has been used for decades (e.g. in pathology), but recent advances with new probes and color deconvolution have allowed the field to grow, although requiring more finesse when being quantitated. The third and most common category of LM is characterized by the use of fluorescent probes targeting biomolecules (specific proteins, DNA, etc) of interest, making them glow with different colors on a black background. Such fluorescent dyes can even be used to monitor subcellular events in real-time. There are many sub-categories of fluorescence microscopy, e.g. confocal, super-resolution, and TIRF (Total Internal Reflectance-induced Fluorescence). Each of these involve specialized technique in sample prep, image acquisition, and/or image analysis. Some NIDDK labs might be comfortable without advanced help on one of more of the techniques described above, and might also be able to set aside a budget for equipment they would use regularly; but to fill any gaps, the NIDDK Advanced Light Microscopy & Image Analysis Core (ALMIAC) remains a reliable resource for cutting-edge light microscopy equipment, software, and expertise. For the FY2025 budget year (October 2024 - September 2025), there were >75 researchers using ALMIAC resources, representing at least 32 (out of 91 in Bethesda, MD; or 35%) "Sections" (individual labs), from at least 12 (out of 17; or 71%) Laboratories and Branches. The user base increased significantly from the previous fiscal year, the largest number of users in any FY since the inception of the NIDDK ALMIAC in 2014. At least 12 of these 75 users were new users to the equipment, requiring training. There were at least 9 NIDDK publications during FY 2025 that used images acquired and/or analyzed with the help of ALMIAC resources: --Qi Zhang, Meng Liu, Yue Xu, Juhyung Lee, Brothely Jones, Bing Li, Wenwei Huang, Yihong Ye & Wei Zheng. Tilorone mitigates the propagation of α-synucleinopathy in a midbrain-like organoid model. J Transl Med. 2024 Sep 2;22(1):816. doi: 10.1186/s12967-024-05551-7. --Jakub Jankowski, Hye Kyung Lee, Chengyu Liu, Julia Wilflingseder & Lothar Hennighausen. Sexually dimorphic renal expression of mouse Klotho is directed by a kidney-specific distal enhancer responsive to HNF1b. Commun Biol. 2024 Sep 14;7(1):1142. doi: 10.1038/s42003-024-06855-6. --Weiqin Yin, Praveen Kumar Rajvanshi, Heather M Rogers, Teruhiko Yoshida, Jeffrey B Kopp, Xiuli An, Max Gassmann, Constance T Noguchi. Erythropoietin regulates energy metabolism through EPO-EpoR-RUNX1 axis. Nat Commun. 2024 Sep 16;15(1):8114. doi: 10.1038/s41467-024-52352-z. --Antwi-Boasiako Oteng, Liu Liu, Yinghong Cui, Oksana Gavrilova, Huiyan Lu, Min Chen, Lee S Weinstein, Jonathan E Campbell, Jo E Lewis, Fiona M Gribble, Frank Reimann, Jürgen Wess. Activation of Gs signaling in mouse enteroendocrine K cells greatly improves obesity- and diabetes-related metabolic deficits. J Clin Invest. 2024 Oct 22;134(24):e182325. doi: 10.1172/JCI182325. --Mana Mohan Mukherjee, Devin Biesbrock, Lara K Abramowitz, Matteo Pavan, Bhoj Kumar, Peter J Walter, Parastoo Azadi, Kenneth A Jacobson, John A Hanover. Selective bioorthogonal probe for N-glycan hybrid structures. Nat Chem Biol. 2024 Oct 28. doi: 10.1038/s41589-024-01756-5. --Amanda Ennis, Lihui Wang, Yue Xu, Layla Saidi, Xiaorong Wang, Clinton Yu, Sijung Yun, Lan Huang, Yihong Ye. NEMF-mediated CAT tailing facilitates translocation-associated quality control. J Cell Biol. 2025 Jun 2;224(6):e202408199. doi: 10.1083/jcb.202408199. -- Dhanush Haspula, Zhenzhong Cui, Srinivas Pittala, Yinghong Cui, Huiyan Lu, Yan Xiong, Jian Jin, Oksana Gavrilova, Eunsang Hwang, Jason Ajwani, Bryan Portillo, Kevin W Williams, Asuka Inoue, Jürgen Wess. G proteins of the G12 family expressed by POMC neurons regulate key metabolic functions. Sci Adv. 2025 Jul 11;11(28):eadu1670. doi: 10.1126/sciadv.adu1670. --Jakub Jankowski, Hye Kyung Lee, Lothar Hennighausen. Y665F variant of mouse Stat5b protects against acute kidney injury through transcriptomic shifts in renal gene expression. Sci Rep. 2025 Aug 21;15(1):30696. doi: 10.1038/s41598-025-15812-0. --Juhyung Lee, Natalie Chin, Jizhong Zou, Wan Nur Atiqah Binti Mazli, Michal Jarnik, Layla Saidi, Yue Xu, Eutteum Jeong, Jessica Suh, John Replogle, Michael E. Ward, Juan S. Bonifacino, Wei Zheng, Ling Hao & Yihong Ye. CHIP protects lysosomes from CLN4 mutant-induced membrane damage. Nat Cell Biol (2025). https://doi.org/10.1038/s41556-025-01738-2 The ALMIAC is in the midst of consolidating, retiring, and acquiring equipment, to improve efficiency and capabilities. Many upgrades are expected for FY26.