Antibody Engineering & Membrane Biophysics in Disease
Group leader
José L. Nieva, Edurne Rujas & Pablo Carravilla
Phone
+34 946 01 3353 | +34 946 01 3429
Address
Biofisika Institute (CSIC, EHU)
Science Park of the EHU
Barrio Sarriena s/n. 48940 Leioa, Bizkaia (Spain)
Research goal
Our laboratory adopts an interdisciplinary approach to counteract the molecular mechanisms underlying disease by combining protein engineering with a deep understanding of the physical properties of cellular membranes.
One major research direction aims to enhance therapeutic antibody efficacy across a range of human diseases, including infectious diseases and cancer. We combine biophysical methods with molecular, structural and cell biology techniques, to elucidate mechanisms underlying antibody-antigen molecular recognition processes that occur within membrane microenvironments. Based on this knowledge, we apply protein engineering to optimize the activity of monoclonal antibodies. Our design strategy integrates biophysical characterization, in vitro functional assays in cellular systems, and preclinical studies in animal models. This iterative optimization process enables us to develop next-generation biological agents that surpass current therapies and advance the field of immunotherapeutics.
In parallel, our Membrane Biophysics in Disease research aims to uncover how the physical properties of cellular membranes influence human pathologies, with a particular focus on rare neurodegenerative disorders and viral infections. Through advanced fluorescence microscopy, we map the biophysical landscape of cell membranes, linking it to cellular dysfunction and exploring its potential for diagnostics, drug discovery and personalized medicine.
Group members
Pablo Carravilla
Ikerbasque Research Fellow
Joao Zulaica
PhD Student
Anne Elizaga
PhD Student
Isabel Gris Cárdenas
Research Technician
Terese Tombelle Gómez
Research Technician
Asier Ramos
PhD Student
Alba Herrero Alonso
Postdoctoral Fellow
Edurne Rujas
Ikerbasque Research Fellow
Ander Ramos
PhD Student
Izaskun Morillo Melero
Phd Student
Jose L Nieva
University Professor
Publications
Domene C, Wiley B, Insausti S, Rujas E, Nieva JL.
Distinctive Membrane Accommodation Traits Underpinning the Neutralization Activity of HIV-1 Antibody against MPER
Mol Pharm. 2025 May 5;22(5):2494-2508
10.1021/acs.molpharmaceut
Domene C, Wiley B, Insausti S, Rujas E, Nieva JL
Distinctive Membrane Accommodation Traits Underpinning the Neutralization Activity of HIV-1 Antibody against MPER
Mol Pharm. 2025 Apr 9
doi: 10.1021/acs.molpharmaceut.4c01341
Domínguez-Meister S, Mediavilla J, Dianova A, Álvarez N, Insausti S, Rujas E, Nieva JL, Brizuela M, Braceras I
High power impulse magnetron sputtering deposited virucide and antibacterial CrN-Cu films and the durability of the antimicrobial activity
Heliyon. 2025 Jan 14;11(2):e41936
doi: 10.1016/j.heliyon.2025.e41936
Alcaraz A, Nieva JL
Viroporins: discovery, methods of study, and mechanisms of host-membrane permeabilization
Q Rev Biophys. 2025 Jan 14;58:e1
doi: 10.1017/S0033583524000192
Insausti S, Ramos-Caballero A, Wiley B, González-Resines S, Torralba J, Elizaga-Lara A, Shamblin C, Ojida A, Caaveiro JMM, Zwick MB, Rujas E, Domene C, Nieva JL.
Generation of a Nonbilayer Lipid Nanoenvironment after Epitope Binding Potentiates Neutralizing HIV-1 MPER Antibody
ACS Appl Mater Interfaces. 2024 Nov 6;16(44):59934-59948
doi: 10.1021/acsami.4c13353
Gladue DP, Gomez-Lucas L, Largo E, Ramirez-Medina E, Torralba J, Queralt-Martín M, Alcaraz A, Velazquez-Salinas L, Nieva JL, Borca MV
Viroporin-like activity of the hairpin transmembrane domain of African swine fever virus B169L protein
J Virol. 2024 Jul 9:e0023124
doi: 10.1128/jvi.00231-24
Suárez-Vega A, Berriozabal G, Perez de Iriarte J, Lorenzo J, Álvarez N, Dominguez-Meister S, Insausti S, Rujas E, Nieva JL, Brizuela M, Braceras I
On the antimicrobial properties and endurance of eugenol and 2-phenylphenol functionalized sol-gel coatings
Heliyon. 2024 Apr 3;10(8):e29146
doi: 10.1016/j.heliyon.2024.e29146
García-Porras M, Torralba J, Insausti S, Valle J, Andreu D, Apellániz B, Nieva JL.
A two-step mechanism for the binding of the HIV-1 MPER epitope by the 10E8 antibody onto biosensor-supported lipid bilayers
FEBS Lett. 2024 Feb 9
doi: 10.1002/1873-3468.14814
Rujas E, Apellániz B, Torralba J, Andreu D, Caaveiro JMM, Wang S, Lu S, Nieva JL.
Liposome-based peptide vaccines to elicit immune responses against the membrane active domains of the HIV-1 Env glycoprotein
Biochim Biophys Acta Biomembr. 2024 Jan;1866(1):184235
doi: 10.1016/j.bbamem.2023.184235
Gladue DP, Gomez-Lucas L, Largo E, Velazquez-Salinas L, Ramirez-Medina E, Torralba J, Queralt M, Alcaraz A, Nieva JL, Borca MV
African Swine Fever Virus Gene B117L Encodes a Small Protein Endowed with Low-pH-Dependent Membrane Permeabilizing Activity
J Virol. 2023 Jun 29;97(6):e0035023
doi: 10.1128/jvi.00350-23
Torralba J, de la Arada I, Partida-Hanon A, Rujas E, Arribas M, Insausti S, Valotteau C, Valle J, Andreu D, Caaveiro JMM, Jiménez MA, Apellániz B, Redondo-Morata L, Nieva JL
Molecular recognition of a membrane-anchored HIV-1 pan-neutralizing epitope
Commun Biol. 2022 Nov 18;5(1):1265
doi: 10.1038/s42003-022-04219-6
Insausti S, Garcia-Porras M, Torralba J, Morillo I, Ramos-Caballero A, de la Arada I, Apellaniz B, Caaveiro JMM, Carravilla P, Eggeling C, Rujas E, Nieva JL
Functional Delineation of a Protein-Membrane Interaction Hotspot Site on the HIV-1 Neutralizing Antibody 10E8
Int J Mol Sci. 2022 Sep 15;23(18):10767
doi: 10.3390/ijms231810767
Rujas E, Cui H, Burnie J, Aschner CB, Zhao T, Insausti S, Muthuraman K, Semesi A, Ophel J, Nieva JL, Seaman MS, Guzzo C, Treanor B, Julien JP.
Engineering pan-HIV-1 neutralization potency through multispecific antibody avidity.
Proc Natl Acad Sci U S A. 2022 Jan 25;119(4):e2112887119
DOI: 10.1073/pnas.2112887119
Rujas E, Leaman DP, Insausti S, Carravilla P, García-Porras M, Largo E, Morillo I, Sánchez-Eugenia R, Zhang L, Cui H, Iloro I, Elortza F, Julien JP, Eggeling C, Zwick MB, Caaveiro JMM, Nieva JL.
Focal accumulation of aromaticity at the CDRH3 loop mitigates 4E10 polyreactivity without altering its HIV neutralization profile.
iScience. 2021 Aug 17;24(9):102987.
DOI: 10.1016/j.isci.2021.102987
Caillat C, Guilligay D, Torralba J, Friedrich N, Nieva JL, Trkola A, Chipot CJ, Dehez FL, Weissenhorn W.
Structure of HIV-1 gp41 with its membrane anchors targeted by neutralizing antibodies.
Elife. 2021 Apr 19;10:e65005.
DOI: 10.7554/eLife.65005
de la Arada I, Torralba J, Tascón I, Colom A, Ubarretxena-Belandia I, Arrondo JLR, Apellániz B, Nieva JL.
Conformational plasticity underlies membrane fusion induced by an HIV sequence juxtaposed to the lipid envelope.
Sci Rep. 2021 Jan 14;11(1):1278.
DOI: 10.1038/s41598-020-80156-w
Largo E, Queralt-Martín M, Carravilla P, Nieva JL, Alcaraz A.
Single-molecule conformational dynamics of viroporin ion channels regulated by lipid-protein interactions.
Bioelectrochemistry. 2021 Feb;137:107641.
DOI: 10.1016/j.bioelechem.2020.107641
Rujas E, Insausti S, Leaman DP, Carravilla P, González-Resines S, Monceaux V, Sánchez-Eugenia R, García-Porras M, Iloro I, Zhang L, Elortza F, Julien JP, Saéz-Cirión A, Zwick MB, Eggeling C, Ojida A, Domene C, Caaveiro JMM, Nieva JL.
Affinity for the Interface Underpins Potency of Antibodies Operating In Membrane Environments.
Cell Rep. 2020 Aug 18;32(7):108037.
DOI: 10.1016/j.celrep.2020.108037
Torralba J, de la Arada I, Carravilla P, Insausti S, Rujas E, Largo E, Eggeling C, Arrondo JLR, Apellániz B, Nieva JL.
Cholesterol Constrains the Antigenic Configuration of the Membrane-Proximal Neutralizing HIV-1 Epitope.
ACS Infect Dis. 2020 Aug 14;6(8):2155-2168.
DOI: 10.1021/acsinfecdis.0c00243
Carravilla P, Nieva JL, Eggeling C.
Fluorescence Microscopy of the HIV-1 Envelope.
Viruses. 2020 Mar 21;12(3):348.
DOI: 10.3390/v12030348
Carravilla P, Darré L, Oar-Arteta IR, Vesga AG, Rujas E, de Las Heras-Martínez G, Domene C, Nieva JL, Requejo-Isidro J.
The Bilayer Collective Properties Govern the Interaction of an HIV-1 Antibody with the Viral Membrane.
Biophys J. 2020 Jan 7;118(1):44-56.
DOI: 10.1016/j.bpj.2019.11.005
Carravilla P, Chojnacki J, Rujas E, Insausti S, Largo E, Waithe D, Apellaniz B, Sicard T, Julien JP, Eggeling C, Nieva JL.
Molecular recognition of the native HIV-1 MPER revealed by STED microscopy of single virions.
Nat Commun. 2019 Jan 8;10(1):78.
DOI: 10.1038/s41467-018-07962-9