Remy Loris Lab

Research focus

The interests of my group encompass the broad area of structure-function relationships in proteins. Although our expertise lies primarily in macromolecular crystallography, the group uses a variety of structural biology and biophysical techniques and is involved in different projects centered around protein structure and molecular recognition. In particular, we are interested in mechanisms of action of intrinsically disordered proteins and in mechanisms of transcription regulation.
Most of our scientific questions are centered around bacterial Toxin-Antitoxin (TA) modules, which we use as model systems. These are operons encoding a stable toxin and a labile antidote. They play a major role in bacterial stress physiology by temporarily halting cell division when nutrients are scarce. They are proposed to be involved in multidrug resistance. Many different families of TA modules exist, differing in the cellular target of the toxin and the nature of the DNA binding domain employed by the antitoxin.

One family, ccdAB, interferes with replication and transcription via interactions with gyrase. This family has been extensively studied in the last five years, leading to a detailed understanding on how the toxin CcdB poisons DNA-bound-gyrase and how the intrinsically disordered domain of the antitoxin CcdA is able to rejuvenated CcdB-poisoned gyrase. The latter proves to be an example on how intrinsically disordered proteins act in mechanistic terms and why intrinsic disorder is required in certain biochemical contexts.

Another family of TA modules, phd/doc, inhibit translation by interfering with the action of the ribosome. The phd/doc module of bacteriophage P1 is being used to study transcription regulation by conditional co-operativity. This is a novel regulatory mechanism used by bacteria that involves allosteric communication between two (partly) disordered protein domains. While such a form of allostery has been predicted based on theoretical arguments, our work provided the first experimental evidence of that such a mechanisms is effectively used by certain organisms.

A second major focus of the group is on intrinsic disorder in plant cell cycle regulation. here we study structure and function of novel families of CDK inhibitors and of inhibitors of the anaphase promoting complex.

Publications

An intrinsically disordered entropic switch determines allostery in Phd-Doc regulationGarcia Pino A, De Gieter S, Talavera Perez A, De Greve H, Efremov R, Loris RNature Chemical Biology, 12, 490-6, 2016
Disorder- and dynamics-based regulatory mechanisms in toxin-antitoxin modulesLoris R, Garcia Pino ACHEMICAL REVIEWS, 114, 6933-47, 2014
The Fic protein Doc uses an inverted substrate to phosphorylate and inactivate EF-TuCastro-Roa D* Garcia Pino A* De Gieter S Van Nuland N Loris R Zenkin NNature Chemical Biology, 9, 811-7, 2013* These authors contributed equally
Energetic basis of uncoupling folding from binding for an intrinsically disordered proteinDrobnak I, De Jonge N, Haesaerts S, Vesnaver G, Loris R, Lah JJOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 135, 1288-94, 2013
Allostery and intrinsic disorder mediate transcription regulation by conditional cooperativityGarcia Pino A, Balasubramanian S, Wyns L, Gazit E, De Greve H, Magnuson R, Charlier D, van Nuland N, Loris RCELL, 142, 101-11, 2010

Job openings

News

Publication in top journal thanks to brand-new NMR Center

09/07/2010 - Flemish scientists put NMR to use to find out how the activity of certain proteins involved in the stress physiology of bacteria is regulated. It led to a breakthrough publication in Cell.

Bacteria pack their own demise

30/07/2009 - Numerous pathogens contain an ‘internal time bomb’, a deadly mechanism that can be used against them.

Remy Loris

Remy Loris

Research area(s)

Bio

​​PhD: Vrije Universiteit Brussel, Brussels, Belgium, '94
Postdoc: Univ. of Leicester, Leicester, UK, '97-'98
Postdoc: CERMAV, Grenoble, France, '98-'99
Postdoc: Vrije Universiteit Brussel, Brussels, Belgium
VIB Project Leader since 2000
Research Professor, Vrije Universiteit Brussel, Belgium since 2003
VIB Expert Scientist since 2009

Contact Info

VIB-VUB Center for Structural BiologyBuilding EPleinlaan 2 1050 BRUSSELRoute description
remy.loris*Replace*With*At*Sign*vub.vib.bePhone: +32 2 629 19 89 / 19 27