Selected Grantee Publications
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- Artificial Intelligence/Machine Learning
- Microscopy
Neutralizing Antibody Vaccine for Pandemic and Pre-Emergent Coronaviruses
Saunders et al., Nature. 2021.
https://doi.org/10.1038/s41586-021-03594-0
SARS-CoV-2 is a new member of the betacoronavirus (beta-CoV) genus, which also includes two common mild beta-CoVs and the life-threatening SARS-CoV-1 and MERS-CoV. Vaccines that elicit protective immunity against SARS-CoV-2 and beta-CoVs that circulate in animals could prevent future pandemics. Researchers designed a novel 24-mer SARS-CoV-2 receptor binding domain-sortase A conjugated nanoparticle vaccine (RBD-scNP). Investigators demonstrated that the immunization of macaques with RBD-scNP, and adjuvanted with 3M-052 and alum, elicits cross-neutralizing antibody responses against bat coronaviruses, SARS-CoV, and multiple SARS-CoV-2 variants of concern. This pioneering approach serves as a multimeric protein platform for the further development of generalized anti-beta-CoV vaccines. Supported by ORIP (U42OD021458), NIAID, and NCI.
Combining In Vivo Corneal Confocal Microscopy With Deep Learning-Based Analysis Reveals Sensory Nerve Fiber Loss in Acute Simian Immunodeficiency Virus Infection
McCarron et al., Cornea. 2021.
https://doi.org/10.1097/ICO.0000000000002661
Researchers characterized corneal subbasal nerve plexus features of normal and simian immunodeficiency virus (SIV)-infected pigtail and rhesus macaques using in vivo confocal microscopy and a deep learning approach for automated assessments. Corneal nerve fiber length and fractal dimension measurements did not differ between species, but pigtail macaques had significantly higher baseline corneal nerve fiber tortuosity than rhesus macaques. Acute SIV infection induced decreased corneal nerve fiber length and fractal dimension in the pigtail macaque model for HIV. Adapting deep learning analyses to clinical corneal nerve assessments will improve monitoring of small sensory nerve fiber damage in numerous clinical contexts, including HIV. Supported by ORIP (U42OD013117) and NINDS.
Cryopreservation Method for Drosophila melanogaster Embryos
Zhan et al., Nature Communications. 2021.
https://www.nature.com/articles/s41467-021-22694-z
Drosophila melanogaster is a premier model for biomedical research. However, preservation of Drosophila stocks is labor intensive and costly. Researchers at University of Minnesota reported an efficient method for cryopreservation by optimizing key steps including embryo permeabilization and cryoprotectant agent loading. This method resulted in more than 10% of embryos developing into fertile adults after cryopreservation for 25 distinct strains from different sources. The further optimization and wide adoption of this protocol will solve the long-standing issue in reliably preserving Drosophila stocks and will significantly impact Drosophila as a model organism for biomedical research. Supported by ORIP (R21OD028758) and NIGMS.
Best Practices for Correctly Identifying Coronavirus by Transmission Electron Microscopy
Bullock et al., Kidney International. 2021.
https://pubmed.ncbi.nlm.nih.gov/33493525/
This paper provides strategies for identifying coronaviruses by transmission electron microscopy in ultrathin sections of tissues or tissue cultures. As illustrated by results in the literature, organ damage may be incorrectly attributed to the presence of virus, since images of coronavirus may resemble subcellular organelles. The paper also references numerous biochemical and imaging techniques to aid an investigator in avoiding pseudo positive identifications. Supported by ORIP (S10OD026776) and others.
A Pulsatile Release Platform Based on Photo-Induced Imine-Crosslinking Hydrogel Promotes Scarless Wound Healing
Zhang et al., Nature Communications. 2021.
https://pubmed.ncbi.nlm.nih.gov/33723267/
Skin wound healing is a dynamic and interactive process involving the collaborative efforts of growth factors, extracellular matrix (ECM), and different tissue and cell lineages. Although accumulating studies with a range of different model systems have increased our understanding of the cellular and molecular basis underlying skin scar formation, they have not been effectively translated to therapy. Development of effective therapeutic approaches for skin scar management is urgently needed. In this study, team of investigators devise a water-oil-water double emulsion strategy to encapsulate proteins within a photo-crosslinkable poly-lactic-co-glycolic acid (PLGA) shell, which can produce microcapsules with pulsatile drug release kinetics after administration. The results show that pulsatile release of the TGF-β inhibitor can accelerate skin wound closure while suppressing scarring in murine skin wounds and large animal preclinical models, suggesting that it could be an effective approach to achieve scarless wound healing in skin. Supported by ORIP (R01OD023700).