Laboratory of Molecular Biophysics

Trip Lab

Desactivado

Dr. Xavier Salvatella

Group Leader

Telephone:

+34 93 40 20459

Email:

xavier.salvatella@irbbarcelona.org

ICREA Research Professor, ERC Consolidator Grant

Meet Our Scientists Videos

Xavier Salvatella: "Magical Choreography"

Research information

Background

Many domains in multi-domain proteins are intrinsically disordered because they do not need to fold to perform their biological functions. This observation challenges the assumption that protein functions are derived from their three-dimensional structures, which dominated thinking in molecular biology since the inception of this field.

Research interests

The laboratory mainly aims to understand the mechanisms by which intrinsically disordered proteins perform their functions. Other aims are to rationalise how specific mutations in these domains lead to disease and to identify strategies allowing drug-like small molecules to inhibit therapeutic targets rich in intrinsic disorder, which are common in oncology and neurology.

The laboratory uses a multidisciplinary approach combining biophysical techniques, theory/molecular simulations, and cell/chemical biology to study the conformations, interactions, and phase transitions of intrinsically disordered proteins of biomedical relevance, in collaboration with partners across the globe.

The research group is keen to host BSc, MSc and PhD students interested in this field, as well as postdoctoral fellows. Applicants should contact Dr. Xavier Salvatella by E-mail to discuss ongoing projects, potential openings and in general to discuss their research interests and plans for future collaboration.

Selected publications

A MEC-2/stomatin condensate liquid-to-solid phase transition controls neuronal mechanotransduction during touch sensing

Sanfeliu-Cerdán, N; Català-Castro, F; Mateos, B; Garcia-Cabau, C; Ribera, M; Ruider, I; Porta-de-la-Riva, M; Canals-Calderón, A; Wieser, S; Salvatella, X; Krieg, M

Nature Cell Biology

(11 )

- -

(2023)

Aberrant phase separation and nucleolar dysfunction in rare genetic diseases

Mensah, MA; Niskanen, H; Magalhaes, AP; Basu, S; Kircher, M; Sczakiel, HL; Reiter, AMV; Elsner, J; Meinecke, P; Biskup, S; Chung, BHY; Dombrowsky, G; Eckmann-Scholz, C; Hitz, MP; Hoischen, A; Holterhus, PM; Hülsemann, W; Kahrizi, K; Kalscheuer, VM; Kan, A; Krumbiegel, M; Kurth, I; Leubner, J; Longardt, AC; Moritz, JD; Najmabadi, H; Skipalova, K; Blok, LS; Tzschach, A; Wiedersberg, E; Zenker, M; Garcia-Cabau, C; Buschow, R; Salvatella, X; Kraushar, ML; Mundlos, S; Caliebe, A; Spielmann, M; Horn, D; Hnisz, D

Nature

614

(7948 )

564 -

(2023)

A glutamine-based single α-helix scaffold to target globular proteins

Escobedo, A; Piccirillo, J; Aranda, J; Diercks, T; Mateos, B; Garcia-Cabau, C; Sánchez-Navarro, M; Topal, B; Biesaga, M; Staby, L; Kragelund, BB; García, J; Millet, O; Orozco, M; Coles, M; Crehuet, R; Salvatella, X

Nature Communications

(1 )

7073 -

(2022)

Small molecules targeting the disordered transactivation domain of the androgen receptor induce the formation of collapsed helical states

Zhu, JQ; Salvatella, X; Robustelli, P

Nature Communications

(1 )

6390 -

(2022)

Nucleus-translocated mitochondrial cytochrome c liberates nucleophosmin-sequestered ARF tumor suppressor by changing nucleolar liquid-liquid phase separation

Gonzalez-Arzola, K; Diaz-Quintana, A; Bernardo-Garcia, N; Martinez-Fabregas, J; Rivero-Rodriguez, F; Casado-Combreras, MA; Elena-Real, CA; Velazquez-Cruz, A; Gil-Caballero, S; Velazquez-Campoy, A; Szulc, E; Gavilan, MP; Ayala, I; Arranz, R; Rios, RM; Salvatella, X; Valpuesta, JM; Hermoso, JA; De la Rosa, MA; Diaz-Moreno, I

Nature Structural & Molecular Biology

(10 )

1024 -

(2022)

Intrinsically disordered proteins and biomolecular condensates as drug targets

Biesaga, M; Frigolé-Vivas, M; Salvatella, X

Current Opinion In Chemical Biology

( )

90 -

100

(2021)

Regulation of biomolecular condensate dynamics by signaling

Garcia-Cabau, C; Salvatella, X

Current Opinion In Cell Biology

( )

111 -

119

(2021)

Hsp70 and Hsp40 inhibit an inter-domain interaction necessary for transcriptional activity in the androgen receptor

Eftekharzadeh, B; Banduseela, VC; Chiesa, G; Martínez-Cristóbal, P; Rauch, JN; Nath, SR; Schwarz, DMC; Shao, H; Marin-Argany, M; Di Sanza, C; Giorgetti, E; Yu, ZG; Pieratelli, R; Felli, IC; Brun-Heath, I; García, J; Nebreda, AR; Gestwicki, JE; Lieberman, AP; Salvatella, X

Nature Communications

(1 )

3562 -

(2019)

Side chain to main chain hydrogen bonds stabilize a polyglutamine helix in a transcription factor

Escobedo, A; Topal, B; Kunze, MBA; Aranda, J; Chiesa, G; Mungianu, D; Bernardo-Seisdedos, G; Eftekharzadeh, B; Gairí, M; Pierattelli, R; Felli, IC; Diercks, T; Millet, O; García, J; Orozco, M; Crehuet, R; Lindorff-Larsen, K; Salvatella, X

Nature Communications

(- )

2034 -

(2019)

Cancer Mutations of the Tumor Suppressor SPOP Disrupt the Formation of Active, Phase-Separated Compartments

Bouchard, JJ; Otero, JH; Scott, DC; Szulc, E; Martin, EW; Sabri, N; Granata, D; Marzahn, MR; Lindorff-Larsen, K; Salvatella, X; Schulman, BA; Mittag, T

Molecular Cell

(1 )

19 -

(2018)

Regulation of Androgen Receptor Activity by Transient Interactions of Its Transactivation Domain with General Transcription Regulators

De Mol, E; Szulc, E; Di Sanza, C; Martínez-Cristóbal, P; Bertoncini, CW; Fenwick, RB; Frigolé-Vivas, M; Masín, M; Hunter, I; Buzón, V; Brun-Heath, I; García, J; De Fabritiis, G; Estébanez-Perpiña, E; McEwan, IJ; Nebreda, AR; Salvatella, X

Structure

(1 )

145 -

(2018)

CPEB4 is regulated during cell cycle by ERK2/Cdk1-mediated phosphorylation and its assembly into liquid-like droplets

Guillén-Boixet, J; Buzon, V; Salvatella, X; Méndez, R

Elife

(e19298 )

e19298 -

(2016)

Sequence Context Influences the Structure and Aggregation Behavior of a PolyQ Tract

Eftekharzadeh, B; Piai, A; Chiesa, G; Mungianu, D; García, J; Pierattelli, R; Felli, IC; Salvatella, X

Biophysical Journal

110

(11 )

2361 -

2366

(2016)

EPI-001, A Compound Active against Castration-Resistant Prostate Cancer, Targets Transactivation Unit 5 of the Androgen Receptor

De Mol, E; Fenwick, RB; Phang, CTW; Buzón, V; Szulc, E; de la Fuente, A; Escobedo, A; García, J; Bertoncini, CW; Estébanez-Perpiñá, E; McEwan, IJ; Riera, A; Salvatella, X

Acs Chemical Biology

(9 )

2499 -

2505

(2016)

Fenwick, RB; Orellana, L; Esteban-Martín, S; Orozco, M; Salvatella, X

Nature Communications

(4070 )

4070 -

(2014)

Projects

Project “Transcription factor condensates as drug targets”, funded by the Mark Foundation for Cancer Research. Reference: ASP-II-4078105378

“ARtin. Discovery of new inhibitors of the disordered domain of the androgen receptor to treat castration-resistant prostate cancer”. El proyecto ARtin, con código INNO20010FRIG, ha recibido financiación del programa AECC Innova promovido por la Fundación Científica AECC

“Modulation of Tau seeding and pathology in tauopathies by BBB-nanocarriers, epitope selective vaccination and ectoPrP Tau receptor bodies” (STOPTauPATHOL) financiado por Fundación "la Caixa". Referencia: LCF/PR/HR19/52160007

"Aprovechamiento de la condensación biomolecular para el descubrimiento de fármacos", financiado por el Ministerio de Ciencia e Innovación, y la Agencia Estatal de Investigación. Ref: PID2019-110198RB-I00 / AEI / 10.13039/501100011033)

"Intrinsically disordered proteins" finançat per l'Agencia de Gestió d'Ajuts Universitaris i de Recerca. Ref: 2021 SGR 00476

"Transiciones líquido sólido en condensados biomoleculares: determinantes moleculares" financiado por el Ministerio de Ciencia e Innovación; la Agencia Estatal de Investigación y el Fondo Europeo de Desarrollo Regional. Referencia: PID2022-141816OB-I00

"Desarrollo de un nuevo fármaco potente y selectivo contra el cáncer de próstata resistente a castración dirigido a la región desordenada del receptor de andrógenos", financiado por MCIN/AEI/10.13039/ 501100011033 y por la Unión Europea “NextGenerationEU”/PRTR. Ref: CPP2022-009651