From elucidating cellular mechanisms underlying tissue regeneration to developing novel biomaterials to improve organ function, Feinberg investigators have provided stunning new snapshots of biological processes invisible to the naked eye.
Here are some of the most striking scientific images from the year.
Understanding How Neurofilaments Clog Up Brain Functions
Northwestern Medicine scientists have uncovered new insights into how neurofilaments act like Velcro in neurodegenerative diseases, clogging up the brain and preventing normal function, according to a study published in the journal JCI Insight. Investigators from the laboratory of Puneet Opal, MD, ‘95 PhD, the Lewis John Pollock Professor of Neurology in the Division of Movement Disorders and of Cell and Developmental Biology, who was senior author of the study, employed a combination of genetic and RNA interference (RNAi) approaches to study the brains of mice which lacked gigaxonin. They observed that the cellular recycling processes were disrupted because the neurofilaments acted like Velcro in the brain, preventing organelles from moving, according to the study. Additionally, the cellular recycling plants — called lysosomes — were missing key digestive enzymes responsible for breaking down waste products, the scientists found. “These vesicles can’t reach the garbage can — lysosomes,” Opal said. “So, the neurofilaments cannot be degraded by that. Additionally, the neurofilaments create docking sites for proteins and organelles normally, but in the disease, these sites are a little bit garbled.”
Caption: Immunofluorescence microscopy from explant culture of dorsal root ganglia (DRGs) isolated from 15-month-old Gan null mice showing neurofilament aggregates (magenta) in the neurons. The satellite glial cells stained with GFAP are in green. The nucleus is counterstained with DAPI (blue). Courtesy of Jean-Michel Paumier.
Caption: Immunofluorescence microscopy of dorsal root ganglia (DRGs) culture from Gan null mice stained for neurofilament light (NFL, in green) seven days in vitro. The nucleus is counterstained with DAPI (white). Courtesy of Jean-Michel Paumier.
New Core to Visualize the Molecular Basis of Human Disease
A new core facility opened to provide Northwestern investigators with access and training to use a Glacios-2 Cryo-Transmission Electron Microscope (X-FEG 200 kV, Falcon 4i detector and Selectris energy filter). The Feinberg Advanced Cryo Electron-Microscopy and Tomography (FACET) core is located in the sub-basement of the Simpson Querrey Biomedical Research Center. The new core will provide access to the Glacios-2 Cryo-Transmission Electron Microscope, ancillary equipment for grid preparation and expertise as a shared resource to enhance research throughout the University. Overall, the new facility will contribute directly to Northwestern’s mission to foster innovation and support investigations into the biological underpinnings of human disease.
Caption: A 3D electron reconstruction and atomic model of the PKD2 ion channel bearing a patient variant.
‘Dancing Molecules’ Treatment Receives FDA Orphan Drug Designation
“Dancing molecules,” the promising new treatment for acute spinal cord injuries developed at Northwestern University, has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA). Developed by regenerative nanomedicine pioneer Samuel I. Stupp, PhD, the therapy harnesses molecular motion to reverse paralysis and repair tissues after traumatic spinal cord injuries. Stupp first introduced the platform in 2021 in a study published in the journal Science. In that study, a one-time injection administered 24 hours after severe injury helped mice regain the ability to walk — just four weeks after treatment.
Caption: A longitudinal spinal cord section treated with the most bioactive therapeutic scaffold. Regenerated axons (shown in red) regrew within the lesion. To administer the treatment, investigators inject the liquid therapy into the region where a spinal cord injury occurred. The liquid then gels into a network of nanofibers, which serve as a scaffold to support cell growth. Courtesy of Samuel I. Stupp, PhD.
Novel Mechanisms Support Cellular Adhesion and Tissue Repair
Northwestern Medicine investigators have discovered new mechanisms underlying cellular adhesion and repair, findings that could inform the development of new therapeutics that boost cellular repair after tissue injury, according to a recent study published in the Journal of Cell Biology. Cara J. Gottardi, PhD, associate professor of Medicine in the Division of Pulmonary and Critical Care and of Cell and Developmental Biology, was senior author of the study.
“These structures immobilize cells in some ways but also allow cell-to-cell contacts to be dynamic. Adhesive junctions have to be strong enough for cells to cohere, but flexible enough to let cells round up and duplicate themselves while also attached to cells that are flattening themselves to migrate and restore the epithelial barrier. Such competing cell behaviors occurring in close proximity can lead to mistakes in cell division, leading to polyploid cells with two or more nuclei. These ‘polyploid mistakes’ are not all bad, since polyploid cells appear to have special properties that favor their role in cell migration and barrier repair.” — Cara J. Gottardi, PhD
Caption: WT-a-cat versus H0-FABD+ cytokinesis failure. Courtesy of Cara J. Gottardi, PhD.
Novel ‘Scaffolding’ Biomaterial Improves Bladder Regeneration and Function
A team of Northwestern scientists has developed an electroactive “scaffolding” material that improves bladder tissue regeneration and organ function better than current techniques, as detailed in a recent study published in Nature Communications. The novel biomaterial could improve outcomes in patients with impaired bladder function with minimal side effects and also reduce the need for additional high-risk surgical procedures, according to Guillermo A. Ameer, ScD, professor of Surgery in the Division of Vascular Surgery and the Daniel Hale Williams Professor of Biomedical Engineering in the McCormick School of Engineering, who was senior author of the study.
“This might be the first example of a cell-free electrically conductive device regenerating an organ. The use of cell-seeded materials often complicates manufacturing and clinical implementation, yet materials without cells commonly do not perform well enough for successful translation to patients. We demonstrate that integrating electrically conductive components into a biodegradable elastomer can lead to a manufacturable material that produces biological and functional results that are on par with the gold standard.” — Guillermo A. Ameer, ScD
Caption: The image shows a conductive scaffold that is functionalized with PEDOT (poly(3,4-ethylenedioxythiophene)) conductive polymer. Biological cells are shown above the material, with the different colors depicting modified cellular activity due to the changing cellular environment. Courtesy of Rebecca Keate, PhD.
Understanding How Hearing Organs Develop
Northwestern Medicine scientists have uncovered how a specific type of cell in the inner ear plays a commanding role in shaping the cellular landscape of the organ responsible for hearing, according to a study published in Science Advances. The research, conducted in mice, focused on the organ of Corti — a finely structured part of the cochlea that converts sound vibrations into electrical signals for the brain. This organ is composed of two types of sensory hair cells and six types of supporting cells, arranged in a precise 11-row mosaic. The study revealed how inner hair cells (IHCs), one of the two sensory cell types, act as developmental architects, guiding the formation and organization of their neighboring supporting cells. “This study transcends the importance it has for hearing and treating deafness,” said Jaime García-Añoveros, PhD, professor of Anesthesiology and Neuroscience and in the Ken and Ruth Davee Department of Neurology, who was senior author of the study. “Using genetic means, we can switch one cell into another and then observe in early, middle, or late development, what it is doing to the other cells that form the organ. This is something that one would want to do in every other organ.”
Caption: This image shows the cytoskeletons of various types of supporting cells, which are intercalated with the hair cells (not shown) and whose identity and precise alignment are dictated in part by the inner hair cells. Courtesy of the García-Añoveros laboratory.
Study Establishes Cell Death as a Driving Force in Glioblastoma
Cell death has been found to be a driving factor in glioblastoma progression, according to a Northwestern-Medicine-led study published in the Proceedings of the National Academy of Sciences. While the relationship between glioblastoma and cell death, also called necrosis, has been established, it had remained unclear whether it contributed to cancer growth or was merely a byproduct of the disease, said Daniel J. Brat, MD, PhD, chair and the Magerstadt Professor of Pathology, who was senior author of the study. “There’s a common phrase in textbooks that the cancer is growing so wildly, so out of control, that it outgrows its blood supply and that the necrosis, the cell death, is an indicator of just how out of control the cancer is. I’ve always thought that was a little bit fishy,” said Brat, who is also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “I think the development of necrosis is a tipping point for this disease. It’s been known for over a hundred years to be the feature under the microscope that correlates with the worst patient outcomes. And so far, nobody has really understood why that is.”
Caption: Central thrombosis and initial necrosis, with surrounding single-cell glioma migration patterns viewed by two-photon microscopy. Courtesy of the Brat laboratory.
Cell Feature Implicated in Cancer Forms Differently than Previously Thought
A team led by scientists at Northwestern University has discovered how paraspeckles, a landmark (condensate) found in the nucleus of cells in many organ systems, form through a different mechanism than the well-established view, a revelation that one day may aid in the design of new cancer drugs. The findings, published in Proceedings of the National Academy of Sciences, propose that rather than its protein components each binding to different parts of an RNA molecule to form a paraspeckle’s layers, proteins in a paraspeckle all prefer the same part of the RNA, creating competition that pushes proteins into their spatial arrangement. “Our work makes an important advancement in our understanding of how condensates are built from their molecular components,” said cell biologist Wilton T. Snead, PhD, assistant professor of Cell and Developmental Biology, who led the research. “Specifically, our study was the first to uncover how combinations of protein-RNA and protein-protein interactions can establish a complex molecular ‘logic’ that dictates condensate form.”
Caption: This image depicts biomolecular condensates reconstituted in vitro with a short fragment of the RNA NEAT1 and the RNA-binding proteins FUS (blue) and TDP-43 (orange). Courtesy of Northwestern University.
Noninvasive Treatment Boosts Immune Response Against Glioblastoma
Northwestern Medicine scientists, along with collaborators from the Washington University School of Medicine, have developed a noninvasive nanomedicine approach that may improve the treatment of glioblastoma, the most aggressive form of brain cancer, according to a recent study published in the Proceedings of the National Academy of Sciences. While immunotherapy has been shown to be effective in many cancers, including lung and breast cancer, it has shown benefit in only a small number of patients with glioblastoma, the most common and aggressive type of primary brain cancer. “Part of the reason for its failure is the fact that high-grade gliomas in the brain lack the target of those immunotherapy drugs, which are killer T-cells. If you have a cancer that lacks those T-cells, or ‘cold tumors,’ then these drugs don't do much,” said Amy Heimberger, MD, PhD, the Jean Malnati Miller Professor of Brain Tumor Research and a co-author of the study. To address this challenge, the scientists, in collaboration with the laboratory of Chad Mirkin, PhD, professor of Medicine in the Division of Hematology and Oncology, the George B. Rathmann Professor of Chemistry at the Weinberg College of Arts and Sciences and director of the International Institute for Nanotechnology, developed a novel spherical nucleic acid (SNA) nanostructure that specifically targets the cGAS enzyme, an upstream target of the STING pathway (Stimulator of Interferon Genes) pathway.
Caption: Scientists at Northwestern Medicine and the Washington University School of Medicine have created a nose-to-brain therapeutic strategy that clears aggressive brain tumors in mice. The approach uses spherical nucleic acids—precisely engineered nanoparticles (red) that move along cranial nerve routes (green) from the nasal passages into the brain, where they stimulate anti-tumor immunity and drive tumor eradication. Courtesy of Alexander Stegh, PhD.
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Credits: Melissa Rohman and Olivia Dimmer