Document text
Principal Investigator: Jeffrey Reece
Organization: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
Fiscal Year: 2022
Award: $521,049
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases
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 17 Laboratories and Branches (i.e. 17 departments with different focus areas) in the NIDDK IRP. 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 FY2021 budget year (October 2021 - September 2022), there were >50 researchers using ALMIAC resources, representing >28 (out of 96) "Sections" (individual labs), from at least 13 (out of 17) Laboratories and Branches. In other words, 75% of NIDDK labs/branches used ALMIAC resources.
Out of the 50+ individual researchers helped, there were at least 9 NIDDK publications during FY 2022 that used images acquired and/or analyzed with the help of ALMIAC resources:
--Temesgen E Andargie, Naoko Tsuji, Fayaz Seifuddin, Moon Kyoo Jang, Peter St Yuen, Hyesik Kong, Ilker Tunc, Komudi Singh, Ananth Charya, Kenneth Wilkins, Steven Nathan, Andrea Cox, Mehdi Pirooznia, Robert A Star, Sean Agbor-Enoh. Cell-free DNA maps COVID-19 tissue injury and risk of death and can cause tissue injury. JCI Insight. 2021 Apr 8;6(7):e147610. PMID:33651717 PMCID:PMC8119224 DOI:10.1172/jci.insight.147610.
--Daniel Chauss, Tilo Freiwald, Reuben McGregor, Bingyu Yan, Luopin Wang, Estefania Nova-Lamperti, Dhaneshwar Kumar, Zonghao Zhang, Heather Teague, Erin E West, Kevin M Vannella, Marcos J Ramos-Benitez, Jack Bibby, Audrey Kelly, Amna Malik, Alexandra F Freeman, Daniella M Schwartz, Didier Portilla, Daniel S Chertow, Susan John, Paul Lavender, Claudia Kemper, Giovanna Lombardi, Nehal N Mehta, Nichola Cooper, Michail S Lionakis, Arian Laurence, Majid Kazemian, Behdad Afzali. Autocrine vitamin D signaling switches off pro-inflammatory programs of TH 1 cells. Nat Immunol. 2022 Jan;23(1):62-74. doi: 10.1038/s41590-021-01080-3. PMID:34764490 PMCID:PMC7612139 DOI:10.1038/s41590-021-01080-3.
--Shue Chen, Leah F Rosin, Gianluca Pegoraro, Nellie Moshkovich, Patrick J Murphy, Guoyun Yu, Elissa P Lei. NURF301 contributes to gypsy chromatin insulator-mediated nuclear organization. Nucleic Acids Res. 2022 Aug 12;50(14):7906-7924. PMID:35819192 PMCID:PMC9371915 DOI:10.1093/nar/gkac600.
--Moriah Eustice, Jeff M. Reece, Daniel Konzman, Salil Ghosh, Jhullian Alston, Tyler Hansen, Andy Golden, Michelle R. Bond, John A. Hanover. Nutrient sensing pathways regulating adult reproductive diapause in C. elegans. PLOS one. In Press (2022).
--Peng Gao, Miao Xu, Qi Zhang, Catherine Z Chen, Hui Guo, Yihong Ye, Wei Zheng, and Min Shen. Graph Convolutional Network-Based Screening Strategy for Rapid Identification of SARS-CoV-2 Cell-Entry Inhibitors. J Chem Inf Model. 2022 Apr 25; 62(8): 19881997. PMID:35404596 PMCID:PMC9016773 DOI:10.1021/acs.jcim.2c00222.
--Juhyung Lee, Yue Xu, Layla Saidi, Miao Xu, Konrad Zinsmaier, Yihong Ye. Abnormal triaging of misfolded proteins by adult neuronal ceroid lipofuscinosis-associated DNAJC5/CSP mutants causes lipofuscin accumulation. Autophagy. 2022 May 4;1-20. PMID:35506243 DOI:10.1080/15548627.2022.2065618.
--Qingcai Meng, Daniel Stoyko, Celine Marlin Andrews, Parthena Konstantinidou, Pavol Genzor, Timothy O, Alexandra R Elchert, Leif Benner, Sushil Sobti, Esther Y Katz, Astrid D Haase. Functional editing of endogenous genes through rapid selection of cell pools (Rapid generation of endogenously tagged genes in Drosophila ovarian somatic sheath cells). Nucleic Acids Res. 2022 Aug 26;50(15):e90. PMID:35639929 PMCID:PMC9410888 DOI:10.1093/nar/gkac448.
--Leah F Rosin, Dahong Chen, Yang Chen, Elissa P Lei. Dosage compensation in Bombyx mori is achieved by partial repression of both Z chromosomes in males. Proc Natl Acad Sci USA. 2022 Mar b;119(10):e2113374119. PMID:35239439 PMCID:PMC8915793 DOI:10.1073/pnas.2113374119
--Qi Zhang, Peter Radvak, Juhyung Lee, Yue Xu, Vivian Cao-Dao, Miao Xu, Wei Zheng, Catherine Z. Chen, Hang Xie & Yihong Ye. Mitoxantrone modulates a heparan sulfate-spike complex to inhibit SARS-CoV-2 infection. Sci Rep 12, 6294 (2022). PMID:35440680 PMCID:PMC9016215 DOI:10.1038/s41598-022-10293-x.
In addition to the specific research projects mentioned above, several areas of improvement in capability and workflow include:
1) Continued deployment of new spinning disk confocal microscope with super-resolution capability, the Nikon CSU-W1 SoRa, which has become the most popular microscope in the ALMIAC.
2) Upgrades to several ALMIAC microscopes, and helping with upgrades to NIDDK microscopes outside the ALMIAC.
3) Conversion of the Huygens deconvolution software to a floating license, available to any NIDDK computer on the internet.
4) With the help of NIDDK CTB (Computer Technology Branch), continued work on the beta version of the NIDDK ALMIAC website.
5) Reorganization of the ALMIAC Director's office and one of the microscope rooms, after a flood forced everything to be moved out.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><21+ years old><3-D><3-Dimensional><3D><Adult><Adult Human><Area><Arizona><Assay><Autocrine Systems><Autophagocytosis><Behavior><Bioassay><Biologic Assays><Biological Assay><Biomedical Research><Blood Diseases><Body Tissues><Bombyx mori><Bone Diseases><Budgets><C elegans><C. elegans><C.elegans><COVID-19><COVID-19 infection><COVID-19 virus><COVID19><COVID19 infection><COVID19 virus><CV-19><CV19><Caenorhabditis elegans><Categories><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Cellular Morphology><Ch'i><Chromatin><Chromosomes><Clinical><CoV-2><CoV2><Color><Complement><Complement Proteins><Complex><Computer software><Computers><DHAQ><DNA><Deoxyribonucleic Acid><Development><Diabetes Mellitus><Diapause><Digestive Diseases><Digestive System Diseases><Digestive System Disorders><Dihydroxyanthracenedione><Dosage Compensation><Dosage Compensation (Genetics)><Drosophila><Drosophila genus><Endocrine Diseases><Endocrine Diseases and Manifestations><Endocrine System Diseases><Equipment><Event><Flooding><Floods><Fluorescence><Fluorescence Agents><Fluorescence Light Microscopy><Fluorescence Microscopy><Fluorescent Agents><Fluorescent Dyes><Fluorescent Probes><GI tract disorder><Generations><Genes><Gypsies><Health><Hematologic Diseases><Hematological Disease><Hematological Disorder><Heparan Sulfate><Heparitin Sulfate><Hepatic Disorder><Image><Image Analyses><Image Analysis><Immunohistochemistry><Immunohistochemistry Cell/Tissue><Immunohistochemistry Staining Method><Individual><Inflammatory><Institutes><Internet><Intracellular Communication and Signaling><Intramural Program><Intramural Research><Intramural Research Program><Investigators><Juvenile Cerebroretinal Degeneration><Kidney Diseases><Knowledge><Laboratories><Lavandula><Lavender><Licensing><Life><Light><Lipofuscin><Liver diseases><Maps><Maryland><Mediating><Metabolic Diseases><Metabolic Disorder><Methods><Microscope><Microscopy><Mission><Mitoxantrone><Mitozantrone><Modeling><Monitor><Moon><NIDDK><NIH><National Institute of Diabetes and Digestive and Kidney Diseases><National Institutes of Health><Nature><Nephropathy><Network-based><Neuronal Ceroid-Lipofuscinosis><Nuclear><Nucleic Acids><Nutrition Disorders><Nutritional Disorders><Organism><Ovarian><Pathology><Pathway interactions><Photoradiation><Preparation><Proteins><Publications><Qi><R-Series Research Projects><R01 Mechanism><R01 Program><Renal Disease><Repression><Research><Research Grants><Research Personnel><Research Project Grants><Research Projects><Research Resources><Research Training><Researchers><Resolution><Resources><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 infection><SARS-CoV-2 inhibitor><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><Scanning><Scientific Publication><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 inhibitor><Severe acute respiratory syndrome related corona virus 2><Side><Signal Transduction><Signal Transduction Systems><Signaling><Slide><Software><Techniques><Technology><Th-1 Cell><Th1 Cells><Thesaurismosis><Time><Tissues><Training><Triage><Type 1 Helper Cell><United States National Institutes of Health><Urinary Tract Diseases><Urologic Diseases><Urologic Disorder><Urological Diseases><Urological Disorders><VIT D><Vitamin D><WWW><Work><Wuhan coronavirus><Yang><aberrant folded protein><aberrant folded proteins><abnormal folded protein><abnormal folded proteins><adulthood><advanced disease><advanced illness><autocrine><autophagy><biological signal transduction><block SARS-CoV-2><block severe acute respiratory syndrome coronavirus 2><blood disorder><bone disorder><cell free DNA><cell free circulating DNA><cell morphology><ceroid lipofuscinosis><colophony><corona virus disease 2019><coronavirus disease 2019><coronavirus disease 2019 infection><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 virus><coronavirus infectious disease-19><death risk><detection of nutrient><developmental><diabetes><digestive disorder><digestive tract disease><disability><endocrine disorder><equipment acquirement><equipment acquisition><equipment investment><equipment procurement><equipment purchase><equipment purchasing><experience><finesse><fluorescent dye/probe><fruit fly><gastrointestinal tract disease><gastrointestinal tract disorder><graph attention network><graph convolutional network><graph neural network><hCoV19><hepatic disease><hepatopathy><hereditary ceroid lipofuscinosis><image evaluation><image interpretation><imaging><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><inhibit SARS-CoV-2><inhibit severe acute respiratory syndrome coronavirus 2><inhibitor><injury to tissue><insight><instrument acquisition><instrument investment><instrument procurement><instrument purchase><interest><kidney disorder><light microscopy><liver disorder><living system><male><metabolism disorder><misfolded protein><misfolded proteins><mortality risk><mutant><nCoV2><nutrient sensing><pathway><perception of nutrients><programs><proteotoxic protein><proteotoxin><renal disorder><reproductive><rosin><screening><service providers><single molecule><technology/technique><three dimensional><tissue injury><tool><urinary tract disorder><web><web site><website><world wide web>