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Design of a universal flu vaccine by antigen reorientation. Influenza hemagglutinin (HA) is reoriented in an “upside-down” configuration to sterically occlude its head and redirect the antibody response to the more exposed stem. https://images.squarespace-cdn.com/content/v1/562d385fe4b0e2b30b0c79b4/5580c355-fb45-475e-ba79-8b52b83c6fc0/ebola.png Research 1 - Make it stand out Figure 2. Design of a universal Ebola vaccine candidate. Eight copies of hyperglycosylated Ebola glycoproteins (GPs) are displayed on each ferritin nanoparticle. Hyperglycosylation is used to direct antibody responses away from variable regions and toward conserved epitopes on GP. https://images.squarespace-cdn.com/content/v1/562d385fe4b0e2b30b0c79b4/3fe8a647-e34b-46a4-bd9f-3e870044bc53/Picture1+%281%29.png Research 1 - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://images.squarespace-cdn.com/content/v1/562d385fe4b0e2b30b0c79b4/6a43d7ec-c1f5-4291-ae0e-23d6ebe3ec41/Spike-ferritin+%281%29.png Research 1 - Make it stand out Figure 4. A structural representation depicting a 24-subunit nanoparticle SARS-CoV-2 vaccine. The figure is based on the H. pylori ferritin crystal structure (rust, PDB 3BVE) and the spike trimer cryo-EM structure (blue, PDB 6VXX). The receptor-binding domain (RBD) of the spike protein is highlighted in dark blue. https://peterkimlab.stanford.edu/research-2 daily 0.75 2024-09-10 https://images.squarespace-cdn.com/content/v1/562d385fe4b0e2b30b0c79b4/92a37765-eefe-48a7-876e-ca9a68d24a83/20220203_Kim%2BLab%2BWebsite%2BFigure-10.1101.2022.01.24.477625v1.png Research 2 - Make it stand out Figure 5. Converting non-neutralizing antibodies into broadly neutralizing antibodies. https://peterkimlab.stanford.edu/research-3 daily 0.75 2025-06-20 https://images.squarespace-cdn.com/content/v1/562d385fe4b0e2b30b0c79b4/17f0700e-f445-4cd5-b3d5-86f361142cb3/Figure%2B2.png Research 3 - Make it stand out Figure 5. Membrane fusion of an enveloped virus and its target cell. https://images.squarespace-cdn.com/content/v1/562d385fe4b0e2b30b0c79b4/393faab9-2ed3-4e67-b1d9-ba21dca922e1/Figure%2B3.png Research 3 - Make it stand out Figure 6. Schematic of membrane fusion mediated by the HIV-1 gp120/gp41 Envelope glycoprotein https://images.squarespace-cdn.com/content/v1/562d385fe4b0e2b30b0c79b4/a481d20b-a4f5-43e3-9d11-ecfb4b7e8440/Figure%2B4.png Research 3 - Make it stand out Figure 7. The pre-hairpin intermediate (PHI). The N-heptad repeat (NHR) and C-heptad repeat (CHR) regions are indicated. Different inhibitors work by binding to various regions of the PHI, thereby preventing formation of the trimer-of-hairpins. (review: Eckert & Kim [2001] Ann. Rev. Biochem.) https://images.squarespace-cdn.com/content/v1/562d385fe4b0e2b30b0c79b4/3f4ba42d-6f28-48cd-bf17-3fa4d87b7c1a/Figure%2B7.png Research 3 - Make it stand out Figure 8. An HIV vaccine approach based on eliciting antibodies that bind to the pre-hairpin intermediate (Eckert et al. [1999] Cell). https://images.squarespace-cdn.com/content/v1/562d385fe4b0e2b30b0c79b4/214e3cc0-b4ac-4bf6-83ae-d3155a774564/Figure%2B8.png Research 3 - Make it stand out Figure 9. D5, an HIV-neutralizing antibody (Miller et al. [2005] PNAS), binds to the gp41 pocket (Luftig et al. [2006] Nature Struct. Mol. Biol.) https://images.squarespace-cdn.com/content/v1/562d385fe4b0e2b30b0c79b4/6addafac-cfc1-4ff9-9fc1-61dea9673fc2/F5.large.jpg Research 3 - Make it stand out Figure 10. Hypothesized mechanism for FcγRI -mediated potentiation of antibodies targeting the NHR region of the PHI. The Fc domain of the antibody is bound by FcγRI , similar to the previously characterized mechanism of FcγRI -mediated potentiation of antibodies targeting the MPER. https://peterkimlab.stanford.edu/research-4 daily 0.75 2024-10-28 https://images.squarespace-cdn.com/content/v1/562d385fe4b0e2b30b0c79b4/a73289e7-840a-47e7-ae62-dcc347f098c0/Home+Page+-+Image+7.jpg Research 4 - Make it stand out Figure 11. (A) A language model learns the likelihood of an amino-acid residue occurring within a sequence context. When trained on millions of protein sequences, a large language model can capture the evolutionary “rules” governing which combinations of amino acids are more likely to appear with each other. (B) An evolutionary landscape can be approximated by a composition of local evolutionary predictions made by a language model, which we refer to as evo-velocity. Evo-velocity can predict the directionality of evolution; for example, evo-velocity analysis of the landscape of cytochrome c sequences recovers the order of various taxonomic classes in the fossil record. (C) Language models can also help guide evolution. By selecting mutations with higher language-model-likelihood than wildtype, we find many that also improve protein function under specific notions of fitness. In particular, we use language models to guide structure- and antigen-agnostic antibody affinity maturation against diverse viral antigens. https://images.squarespace-cdn.com/content/v1/562d385fe4b0e2b30b0c79b4/a71a4aab-8c70-4b68-b6b3-ec2cd11a40c2/Figure+1+-+ABC.jpg Research 4 - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://images.squarespace-cdn.com/content/v1/562d385fe4b0e2b30b0c79b4/b85b694a-a1ab-4185-917c-5ab79643a006/8.jpg Research 4 - Make it stand out Figure 12. We utilize a structure-informed language model to consider the inverse folding task of predicting amino acid sequence from protein backbone structure and indirectly explore protein function fitness landscapes. For protein engineering tasks, this allows us to constrain directed evolution exploration to regimes where the protein fold is preserved. We demonstrate the effectiveness of this method to evolve antibodies for improved potency and resilience against viral escape variants. https://peterkimlab.stanford.edu/talks daily 0.75 2025-06-20 https://peterkimlab.stanford.edu/technical-repository daily 0.75 2026-03-31