The Institute for Protein Innovation (IPI) brought its Antibodies Roadshow back for a second year on November 15 during the 2025 Society for Neuroscience meeting in San Diego. Set aboard the historic USS Midway, the workshop gathered leading neuroscientists for an intimate exchange of published and emerging research, with conversations centered on the latest technologies and the pressing need for better protein tools — especially antibodies — to advance studies in synaptic biology, neuronal circuitry and development.
As a nonprofit dedicated to applied protein research, tool development and education, IPI continues to identify and address gaps in the availability of high-quality reagents and the knowledge of how to best use them. Events like the Antibodies Roadshow provide a forum to engage directly with the research community, spotlight priority challenges and shape the development of new antibodies and protein tools that can accelerate discovery across neuroscience.
Here are the highlights from this year’s event:
Successful community validation
Mike Walden, director of commercialization at IPI, kicked off the meeting, offering an overview of IPI and its community approach to discovering and validating recombinant antibodies. He highlighted the case of IPI antibodies generated against neurexin and neuroligin, two protein families that are essential for neurons to transmit signals across synapses. Neuroscientists in the community tested these antibodies and shared assay results at a series of three virtual workshops convened by IPI. Thanks to their input, IPI was able to hone the antibodies’ performance and produce the first batch of anti-neurexin and anti-neuroligin antibodies, released in November 2025 as part of the synaptic cleft collection.
A picture holds a thousand neurons
Zhuhao Wu from Weill Cornell Medicine showed stunning, three-dimensional views of the insides of mouse brains — without having to cut or deform their structure. He performed the feat using a tissue-clearing process that renders organs transparent, followed by immunohistochemistry with antibodies. Wu’s images help illuminate the identity, distribution and spatial arrangement of both neuronal and non-neuronal cells. The next step is to image human brains using a technique dubbed HuB.Clear (Human Brain Clearing). For that, he needs large quantities (tens of milligrams) of antibodies and is looking to organizations such as IPI and Neuromab to deliver open-source recombinants.
Mapping connections with barcodes
Having co-founded e11 Bio, a focused non-profit developing tools for mapping brain circuits, Andrew Payne presented his team’s development of a protein barcode platform that self-corrects neuron tracing maps. Wielding a picture of a grid overlaying a Bay Area subway map, Payne compared the train routes to neuronal axons and dendrites, snaking through tissue to connect to other neuronal cells. Tracing these cellular connections gets expensive, the largest costs arising when the dendritic trace in any microscopic grid square is faulty, requiring proofreading and manual correction.
Referencing a preprint now online, Payne presented his team’s solution, called PRISM, which integrates protein barcoding, expansion microscopy and machine learning. The barcoding relies on epitope tag antibodies, such as those provided by IPI through Addgene. The scheme allows each neuron to be labeled with a unique combination of protein tags, or a cellular ID, that distinguishes it from adjacent neurons. AI can then segment and proofread the traces, resulting in cheaper, faster, higher-resolution images of neuronal architecture studded with synaptic features.
Painting molecular portraits of the brain
Karel Svoboda, from the Allen Institute for Neural Dynamics, described his team’s work painting “molecular portraits of the synaptome.” The effort relies on advances in tissue processing, labeling and fluorescence microscopy, including his team’s development of a highly advanced microscope, ExA-SPIM. When combined with novel tissue-clearing and expansion methods, the instrument enables imaging of entire mouse brains with high contrast, without sectioning. His team is testing new affinity reagents to localize proteins within synapses to help identify what and where the different types of synapses are. These reagents include antibodies recently developed by IPI for neurexins and neuroligins. He also described new work with AI-guided protein design to develop novel affinity reagents.
An architecture of biochemical activity
Jin Zhang from the University of California, San Diego, described her team’s exploration of biochemical activity not as a function but rather an architecture. If one can map protein activity in space and time, one might better understand disease states, which Zhang views as disruptions of this architecture. To do this mapping, Zhang’s team designed a series of biosensors based on genetically encoded Förster Resonance Energy Transfer (FRET). In one instance, her team tagged proteins with fluorescent reporters that have a spectral overlap. When proteins are close together, their overlap activates FRET. Zhang presented her team’s efforts to design many novel sensors, including those that detect the activity of Ras, a critical regulator of cell growth and proliferation in cancer. The biosensors are ideal for multiplexing, enabling functional super-resolution imaging.
Synaptic players in Alzheimer’s Disease
Yimin Zou from the University of California, San Diego, offered a vivid look into his team’s deep exploration of planar cell polarity (PCP) — a directed cell-to-cell communication pathway central to building and maintaining glutamatergic synapses. He described how PCP protein families such as Celsr, Frizzled and Prickle assemble into an asymmetric transsynaptic complex that helps spark and stabilize most glutamatergic synapses across the hippocampus and cortex. In contrast, the protein Vangl2 works as a disruptor, breaking apart this complex and driving synapse disassembly. He also presented new findings showing the interactions between Celsr, Frizzled, Vangl2 and amyloid-β (Aβ), a protein that plays a central — but complex — role in Alzheimer’s disease (AD).
Sources:
Mike Walden, mike.walden@proteininnovation.org
Zhuhao Wu, zhw4007@med.cornell.edu
Andrew Payne, hello@e11.bio
Karel Svoboda, karel.svoboda@alleninstitute.org
Jin Zhang, jzhang32@ucsd.edu
Yimin Zou, yzou@ucsd.edu
Writer: Trisha Gura, trisha.gura@proteininnovation.org
About IPI
The Institute for Protein Innovation is pioneering a new approach to scientific discovery and collaboration. As a nonprofit research institute, we provide the biomedical research community with synthetic antibodies and deep protein expertise, empowering scientists to explore fundamental biological processes and pinpoint new targets for therapeutic development. Our mission is to advance protein science to accelerate research and improve human health. For more information, visit proteininnovation.org or follow us on social media, @ipiproteins.