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Staff member

Mariano Martín Gomez

Protein phase transitions in health and disease
Staff member publications

Martín, Mariano, Bolognesi, Benedetta, (2025). Massive mutagenesis reveals an incomplete amyloid motif in Bri2 that turns amyloidogenic upon C-terminal extension Proceedings Of The National Academy Of Sciences Of The United States Of America 122, e2415521122

Bolognesi, Benedetta

JTD

Thompson, Mike, Martín, Mariano, Olmo, Trinidad Sanmartín, Rajesh, Chandana, Koo, Peter K., Bolognesi, Benedetta, Lehner, Ben, (2025). Massive experimental quantification allows interpretable deep learning of protein aggregation Science Advances 11, eadt5111

Protein aggregation is a pathological hallmark of more than 50 human diseases and a major problem for biotechnology. Methods have been proposed to predict aggregation from sequence, but these have been trained and evaluated on small and biased experimental datasets. Here we directly address this data shortage by experimentally quantifying the aggregation of >100,000 protein sequences. This unprecedented dataset reveals the limited performance of existing computational methods and allows us to train CANYA, a convolution-attention hybrid neural network that accurately predicts aggregation from sequence. We adapt genomic neural network interpretability analyses to reveal CANYA’s decision-making process and learned grammar. Our results illustrate the power of massive experimental analysis of random sequence-spaces and provide an interpretable and robust neural network model to predict aggregation.

JTD

Groeneweg, Stefan, van Geest, Ferdy S., Martín, Mariano, Dias, Mafalda, Frazer, Jonathan, Medina-Gomez, Carolina, Sterenborg, Rosalie BTM., Wang, Hao, Dolcetta-Capuzzo, Anna, de Rooij, Linda J., Teumer, Alexander, Abaci, Ayhan, van den Akker, Erica LT., Ambegaonkar, Gautam P., Armour, Christine M., Bacos, Iiuliu, Bakhtiani, Priyanka, Barca, Diana, Bauer, Andrew J., van den Berg, Sjoerd AA., van den Berge, Amanda, Bertini, Enrico, van Beynum, Ingrid M., Brunetti-Pierri, Nicola, Brunner, Doris, Cappa, Marco, Cappuccio, Gerarda, Castellotti, Barbara, Castiglioni, Claudia, Chatterjee, Krishna, Chesover, Alexander, Christian, Peter, Coenen-van der Spek, Jet, de Coo, Irenaeus FM., Coutant, Regis, Craiu, Dana, Crock, Patricia, DeGoede, Christian, Demir, Korcan, Dewey, Cheyenne, Dica, Alice, Dimitri, Paul, Dremmen, Marjolein HG., Dubey, Rachana, Enderli, Anina, Fairchild, Jan, Gallichan, Jonathan, Garibaldi, Luigi, George, Belinda, Gevers, Evelien F., Greenup, Erin, Hackenberg, Annette, Halász, Zita, Heinrich, Bianka, Hurst, Anna C., Huynh, Tony, Isaza, Amber R., Klosowska, Anna, van der Knoop, Marieke M., Konrad, Daniel, Koolen, David A., Krude, Heiko, Kulkarni, Abhishek, Laemmle, Alexander, LaFranchi, Stephen H., Lawson-Yuen, Amy, Lebl, Jan, Leeuwenburgh, Selmar, Linder-Lucht, Michaela, López Martí, Anna, Lorea, Cláudia F., Lourenço, Charles M., Lunsing, Roelineke J., Lyons, Greta, Malikova, Jana Krenek, Mancilla, Edna E., McCormick, Kenneth L., McGowan, Anne, Mericq, Veronica, Lora, Felipe Monti, Moran, Carla, Muller, Katalin E., Nicol, Lindsey E., Oliver-Petit, Isabelle, Paone, Laura, Paul, Praveen G., Polak, Michel, Porta, Francesco, Poswar, Fabiano O., Reinauer, Christina, Rozenkova, Klara, Seckold, Rowen, Seven Menevse, Tuba, Simm, Peter, Simon, Anna, Singh, Yogen, Spada, Marco, Stals, Milou AM., Stegenga, Merel T., Stoupa, Athanasia, Subramanian, Gopinath M., Szeifert, Lilla, Tonduti, Davide, Turan, Serap, Vanderniet, Joel, van der Walt, Adri, Wémeau, Jean-Louis, van Wermeskerken, Anne-Marie, Wierzba, Jolanta, de Wit, Marie-Claire Y., Wolf, Nicole I., Wurm, Michael, Zibordi, Federica, Zung, Amnon, Zwaveling-Soonawala, Nitash, Rivadeneira, Fernando, Meima, Marcel E., Marks, Debora S., Nicola, Juan P., Chen, Chi-Hua, Medici, Marco, Visser, WEdward, (2025). Mapping variants in thyroid hormone transporter MCT8 to disease severity by genomic, phenotypic, functional, structural and deep learning integration Nature Communications 16, 2479

Visser, W. Edward

JTD

Basas, J., Morer, A., Ratia, C., Martín, M.T., del Pozo, J.L., Gomis, X., Rojo-Molinero, E., Torrents, E., Almirante, B., Gavaldà, J., (2016). Efficacy of anidulafungin in the treatment of experimental Candida parapsolosis catheter infection Journal of Antimicrobial Chemotherapy , 71, (10), 2895-2901

Objectives The effectiveness of anidulafungin versus liposomal amphotericin B (LAmB) for treating experimental Candida parapsilosis catheter-related infection by an antifungal-lock technique was assessed. Methods Two clinical strains of C. parapsilosis (CP12 and CP54) were studied. In vitro studies were used to determine the biofilm MICs (MBIC50 and MBIC90) by XTT reduction assay and LIVE/DEAD biofilm viability for anidulafungin and LAmB on 96-well microtitre polystyrene plates and silicone discs. An intravenous catheter was implanted in New Zealand white rabbits. Infection was induced by locking the catheter for 48 h with the inoculum. The 48 h antifungal-lock treatment groups included control, 3.3 mg/mL anidulafungin and 5.5 mg/mL LAmB. Results Anidulafungin showed better in vitro activity than LAmB against C. parapsilosis growing in biofilm on silicone discs. MBIC90 of LAmB: CP12, >1024 mg/L; CP54, >1024 mg/L. MBIC90 of anidulafungin: CP12, 1 mg/L; CP54, 1 mg/L (P ≤ 0.05). Moreover, only anidulafungin (1 mg/L) showed >90% non-viable cells in the LIVE/DEAD biofilm viability assay on silicone discs. No differences were observed between the in vitro susceptibility of anidulafungin or LAmB when 96-well plates were used. Anidulafungin achieved significant reductions relative to LAmB in log10 cfu recovered from the catheter tips for both strains (P ≤ 0.05). Only anidulafungin achieved negative catheter tip cultures (CP12 63%, CP54 73%, P ≤ 0.05). Conclusions Silicone discs may be a more reliable substrate for the study of in vitro biofilm susceptibility of C. parapsilosis. Anidulafungin-lock therapy showed the highest activity for experimental catheter-related infection with C. parapsilosis.

JTD

Five peptide sequences corresponding to the E1 protein of GBV-C [NCCAPEDIGFCLEGGCLV (P7), APEDIGFCLEGGCLVALG (P8), FCLEGGCLVALGCTICTD (P10), QAGLAVRPGKSAAQLVGE (P18), and AQLVGELGSLYGPLSVSA (P22)] were synthesized because they were capable of interfering with the HIV-1 fusion peptide (HIV-1 FP)-vesicle interaction. In this work the interaction of these peptides with the HIV-1 FP, as well as with membrane models, was analyzed to corroborate their inhibition ability and to understand if the interaction with the fusion peptide takes place in solution or at the membrane level. Several studies were carried out on aggregation and membrane fusion, surface Plasmon resonance, and conformational analysis by circular dichroism. Moreover, in vitro toxicity assays, including cytotoxicity studies in 3T3 fibroblasts and hemolysis assays in human red blood cells, were performed to evaluate if these peptides could be potentially used in anti-HIV-1 therapy. Results show that P10 is not capable of inhibiting membrane fusion caused by HIV-1 and it aggregates liposomes and fuses membranes, thus we decided to discard it for futures studies. P18 and P22 do not inhibit membrane fusion, but they inhibit the ability of HIV-1 FP to form pores in bilayers, thus we have not discarded them yet. P7 and P8 were selected as the best candidates for future studies because they are capable of inhibiting membrane fusion and the interaction of HIV-1 FP with bilayers. Therefore, these peptides could be potentially used in future anti-HIV-1 research. Part of the gang: Liposomes are deposited on a surface plasmon resonance chip (see AFM image of the chip) to observe the interaction of peptides corresponding to the E1 envelop protein of the hepatitis G virus with membranes to show how they reduce the interaction of the HIV-1 fusion peptide.

JTD Keywords: HIV-1 fusion protein, Liposomes, Membranes, Peptides, Viruses