Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy

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Computational study of transcription factor binding sites

Any living organism contains a whole set of instructions encoded as genes on the DNA. This set of instructions contains all the necessary information that the organism will ever need, from its development to a mature individual to environment specific resp ...

EPFL2020

TBK1 phosphorylates mutant Huntingtin and suppresses its aggregation and toxicity in Huntington's disease models

Hilal Lashuel, Anass Chiki, Johan Auwerx, Ramanath Narayana Hegde, Laurent Mouchiroud, Lara Petricca

Phosphorylation of the N‐terminal domain of the huntingtin (HTT ) protein has emerged as an important regulator of its localization, structure, aggregation, clearance and toxicity. However, validation of the effect of bona fide phosphorylation in vivo and ...

2020

Single-molecule studies of amyloid proteins: from biophysical properties to diagnostic perspectives

Chan Cao

In neurodegenerative diseases, a wide range of amyloid proteins or peptides such as amyloid-beta and alpha-synuclein fail to keep native functional conformations, followed by misfolding and self-assembling into a diverse array of aggregates. The aggregates ...

CAMBRIDGE UNIV PRESS2020

Development of chemical biology tools to reveal the function and organization of the silenced chromatin state

Nora Guidotti

Effector proteins are recruited to chromatin via transient interactions between their reader domains and histone post-translational modification (PTM) patterns. These interactions form signaling pathways that control gene expression or repression and which ...

EPFL2020

Roles of Epigenetic Dysregulation in Cancer Progression and Metastasis

Mohammad Sadegh Saghafinia

Nearly all the cells of an organism share the same DNA sequence or genome, and yet they show different phenotypes and carry out different functions. This diversity is made possible by a verity of molecular modifications acting on the DNA sequence that coll ...

EPFL2020

Enhanced flux prediction by integrating relative expression and relative metabolite abundance into thermodynamically consistent metabolic models

Vassily Hatzimanikatis, Noushin Hadadi, Vikash Kumar Pandey

The ever-increasing availability of transcriptomic and metabolomic data can be used to deeply analyze and make ever-expanding predictions about biological processes, as changes in the reaction fluxes through genome-wide pathways can now be tracked. Current ...

2019

Properties of LINE-1 proteins and repeat element expression in the context of amyotrophic lateral sclerosis

Didier Trono, Priscilla Turelli, Evaristo Jose Planet Letschert

BackgroundAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving loss of motor neurons and having no known cure and uncertain etiology. Several studies have drawn connections between altered retrotransposon expression and ALS. C ...

2018

Dynamic protein-chromatin interactions in heterochromatin and during the DNA damage response on the single molecule level

Andreas Linus Bachmann

Dynamic regulation of chromatin, a structure consisting of DNA and histone proteins, is mediated through histone post-translational modifications (PTMs) and effector proteins. HP1a and PRC2 are recruited to repressive PTMs (H3K9me3, H3K27me3) and enable he ...

EPFL2018

DNA repair protein Rad18 restricts LINE-1 mobility

Priscilla Turelli

Long interspersed element-1 (LINE-1, L1) is a mobile genetic element comprising about 17% of the human genome. L1 utilizes an endonuclease to insert L1 cDNA into the target genomic DNA, which induces double-strand DNA breaks in the human genome and activat ...

Nature Research2018

Polyglutamine expansion affects huntingtin conformation in multiple Huntington’s disease models

Hilal Lashuel, Sean Michael Deguire, Lara Petricca

Conformational changes in disease-associated or mutant proteins represent a key pathological aspect of Huntington's disease (HD) and other protein misfolding diseases. Using immunoassays and biophysical approaches, we and others have recently reported that ...

Springer Nature2017

The role of the polyglutamine and N-terminal domains in regulating the aggregation and structural properties of Huntingtin Exon 1

Sophie Vieweg

Huntington Disease (HD) is caused by a CAG repeat expansion in the huntingtin gene leading to the formation of mutant Huntingtin protein (Htt) with an expanded polyglutamine (polyQ) domain (>36Q). Generation of short N-terminal Htt fragments by proteolysis ...

EPFL2017

Monomeric Huntingtin Exon 1 Has Similar Overall Structural Features for Wild-Type and Pathological Polyglutamine Lengths

Hilal Lashuel, John Blaine Warner IV

Huntington’s disease is caused by expansion of a polyglutamine (polyQ) domain within exon 1 of the huntingtin gene (Httex1). A popular hypothesis is that the Httex1 protein undergoes sharp conformational changes as the polyQ length exceeds a threshold of 3 ...

2017

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