Daniel Otzen

Daniel Otzen
Aarhus University | AU

About

384
Publications
47,339
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18,308
Citations
Citations since 2016
105 Research Items
9285 Citations
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201620172018201920202021202202004006008001,0001,2001,400
201620172018201920202021202202004006008001,0001,2001,400
201620172018201920202021202202004006008001,0001,2001,400

Publications

Publications (384)
Article
Bacterial functional amyloids contribute to biofilm development by bacteria and provide protection from the immune system and prevent antibiotic treatment. Strategies to target amyloid formation and interrupt biofilm formation have attracted recent interest due to their antimicrobial potential. Functional amyloid in Pseudomonas (Fap) includes FapC...
Article
Functional amyloid, which unlike its pathological counterpart serves a biological purpose, is produced in a carefully orchestrated sequence of events. In bacteria, the major amyloid component is transported over the periplasm and through the outer membrane to assemble on the bacterial cell surface. During its life time, the amyloid protein may be e...
Article
Functional amyloids (FA) are proteins which are evolutionarily optimized to form highly stable fibrillar structures that strengthen the bacterial biofilm matrix. FA such as CsgA (E. coli) and FapC (Pseudomonas) are secreted to the bacterial surface where they integrate into growing fibril structures projecting from the outer membrane. FA are expose...
Article
Full-text available
Despite extensive research, the molecular mechanisms underlying the toxicity of αSN in Parkinson’s disease (PD) pathology are still poorly understood. To address this, we used a microarray dataset to identify genes that are induced and differentially expressed after exposure to toxic αSN aggregates, which we call exogenous αSN response (EASR) genes...
Preprint
Full-text available
The role of the blood-brain barrier (BBB) is to control trafficking of biomolecules and protect the brain. This function can be compromised by pathological conditions. Parkinson’s disease (PD) is characterized by the accumulation of α-synuclein aggregates (αSN-AGs) such as oligomers and fibrils, which contribute to disease progression and severity....
Preprint
Full-text available
Parkinson's disease (PD) is the second most common neurodegenerative disease. The presence of lewy bodies, primarily consisting of α-synuclein (α-syn) aggregates is one of the common features seen in the substantia nigra region of the brain in PD patients. The disease remains incurable and only symptomatic relief is available. We screened various c...
Article
Full-text available
Functional amyloid is produced by many organisms but is particularly well understood in bacteria, where proteins such as CsgA (E. coli) and FapC (Pseudomonas) are assembled as functional bacterial amyloid (FuBA) on the cell surface in a carefully optimized process. Besides a host of helper proteins, FuBA formation is aided by multiple imperfect rep...
Preprint
The aberrant folding of proteins into amyloid aggregates is associated with over 50 diseases. The amyloid aggregation of α-synuclein (αS), related to Parkinson’s disease, can be catalyzed by lipid-membrane surfaces. Despite the importance of lipid surfaces and several decades of structural studies, the 3D-structure of lipid-membrane bound αS is sti...
Article
Full-text available
Parkinson’s disease is mainly caused by aggregation of α-synuclein (α-syn) in the brain. Exchange of α-syn between the brain and peripheral tissues could have important pathophysiological and therapeutic implications, but the trafficking mechanism of α-syn across the blood brain-barrier (BBB) remains unclear. In this study, we therefore investigate...
Article
Full-text available
Glycation is a non-enzymatic posttranslational modification (PTM) known to be increased in the brains of hyperglycemic patients. α-synuclein (αSN), a central player in the etiology of Parkinson’s disease (PD), can be glycated at lysine residues, thereby reducing αSN fibril formation in vitro and modulating αSN aggregation in cells. However, the mol...
Article
Full-text available
Hypothesis Lipases are widely used in the detergent industry and must withstand harsh conditions involving both anionic and zwitterionic surfactants at alkaline pH. Thermomyces lanuginosus lipase (TlL) is often used and stays active at high concentrations of the anionic surfactant sodium dodecyl sulfate (SDS) at pH 8.0, but is sensitive to SDS at p...
Article
Full-text available
Amyloid proteins are widespread in nature both as pathological species involved in several diseases and as functional entities that can provide protection and storage for the organism. Lipids have been found in amyloid deposits from various amyloid diseases and have been shown to strongly affect the formation and structure of both pathological and...
Article
Unlike misfolding in neurodegenerative diseases, aggregation of functional amyloids involved in bacterial biofilm, e.g. CsgA (E. coli) and FapC (Pseudomonas), is carefully regulated. However, it is unclear whether functional aggregation is inhibited by chaperones targeting pathological misfolding and if so by what mechanism. Here we analyze how fou...
Article
Full-text available
Excessive discharge of synthetic azo dyes into the aquatic ecosystem is a global concern. Here, we develop a green approach to remediate dye pollutants by fabricating an easily separable bio-nanocomposite, based on nanofibrils from whey protein concentrate together with montmorillonite. The nanocomposite was characterized using scanning electron mi...
Article
Functional bacterial amyloids (FuBA) are intrinsically disordered proteins (IDPs) which rapidly and efficiently aggregate, forming extremely stable fibrils. The conversion from IDP to amyloid is evolutionarily optimized and likely couples folding to association. Many FuBA contain several imperfect repeat sequences which contribute to the stability...
Article
Full-text available
Biofilms enable bacteria to colonize numerous ecological niches. Bacteria within a biofilm are protected by the extracellular matrix (ECM), of which the fibril-forming amyloid protein curli and polysaccharide cellulose are major components in members of Salmonella, Eschericha and Mycobacterium genus. A shortage of real-time detection methods has li...
Article
Full-text available
Aggregated α-synuclein (α-syn) is the main constituent of Lewy bodies, which are a pathological hallmark of Parkinson’s disease (PD). Environmental factors are thought to be potential triggers capable of initiating the aggregation of the otherwise monomeric α-syn. Braak’s seminal work redirected attention to the intestine and recent reports of dysb...
Article
Microfluidic systems under laminar flow conditions provide in-solution information about species size and binding affinities at very modest sample costs. Flow-induced dispersion analysis directly measures the spread of the analyte profile using Taylor dispersion analysis, whereas microfluidic diffusional sizing quantifies the transfer of analyte fr...
Article
Empirically α-helical membrane protein folding stability in surfactant micelles can be tuned by varying the mole fraction MFSDS of anionic (sodium dodecyl sulfate, SDS) relative to nonionic (e.g. dodecyl maltoside, DDM) surfactant, but we lack a satisfying physical explanation of this phenomenon. Cysteine labeling (CL) has thus far only been used t...
Article
Full-text available
Phenol-soluble modulins (PSMs) such as α-PSMs, β-PSMs, and δ-toxin are virulence peptides secreted by different Staphylococcus aureus strains. PSMs are able to form amyloid fibrils, which may strengthen the biofilm matrix that promotes bacterial colonization of and extended growth on surfaces (e.g. cell tissue) and increases antibiotic resistance....
Article
Full-text available
Pathology consisting of intracellular aggregates of alpha-Synuclein (α-Syn) spread through the nervous system in a variety of neurodegenerative disorders including Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. The discovery of structurally distinct α-Syn polymorphs, so-called strains, supports a hypothesis where strai...
Article
Full-text available
We propose a computational investigation on the interaction mechanisms between SARS-CoV-2 spike protein and possible human cell receptors. In particular, we make use of our newly developed numerical method able to determine efficiently and effectively the relationship of complementarity between portions of protein surfaces. This innovative and gene...
Article
Cross-seeding between amyloidogenic proteins in the gut is receiving increasing attention as a possible mechanism for initiation or acceleration of amyloid formation by aggregation-prone proteins such as αSN, which is central in the development of Parkinson's disease. This is particularly pertinent in view of the growing number of functional (i.e....
Article
Chemical glycosylation of proteins is a powerful tool applied widely in biomedicine and biotechnology. However, it is a challenging undertaking and typically relies on recombinant proteins and site‐specific conjugations. The scope and utility of this nature‐inspired methodology would be broadened tremendously by the advent of facile, scalable techn...
Article
Full-text available
Formation of amyloid structures is originally linked to human disease. However, amyloid materials are found extensively in the animal and bacterial world where they stabilize intra‐ and extra‐cellular environments like biofilms or cell envelopes. To date, functional amyloids have largely been studied using optical microscopy techniques in vivo, or...
Article
Full-text available
The intrinsically disordered human protein α-synuclein (αSN) can self-associate into oligomers and amyloid fibrils. Several lines of evidence suggest that oligomeric αSN is cytotoxic, making it important to devise strategies to either prevent oligomer formation and/or inhibit the ensuing toxicity. (–)-epigallocatechin gallate (EGCG) has emerged as...
Preprint
Full-text available
Cross-seeding between amyloidogenic proteins in the gut is receiving increasing attention as a possible mechanism for initiation or acceleration of amyloid formation by aggregation-prone proteins such as αSN, which is central in the development of Parkinson’s disease. This is particularly pertinent in view of the growing number of functional ( i.e....
Article
Full-text available
Nanoparticles are useful for increasing drug stability, solubility, and availability. The small molecule baicalein inhibits fibrillation, and detoxifies aggregates of α-synuclein (αSN) associated with Parkinson's disease (PD), but it suffers from instability, low solubility and consequent low availability. Here it is demonstrated that incorporation...
Article
Full-text available
The thermodynamic hypothesis of protein folding, known as the “Anfinsen’s dogma” states that the native structure of a protein represents a free energy minimum determined by the amino acid sequence. However, inconsistent with the Anfinsen’s dogma, globular proteins can misfold to form amyloid fibrils, which are ordered aggregates associated with di...
Article
Full-text available
Thanks in large part to the seminal work of Steve White and his colleagues, we appreciate the “ordered complexity” of the lipid bilayer and how it impacts the incorporation of integral membrane proteins as well as more peripherally associated proteins. Steve’s work also provides a vital foundation to tackle another challenge: cytotoxic oligomeric c...
Article
Alpha-synuclein (α-syn) is a 140 amino acid, intrinsically disordered protein with a potential role in neurotransmitter vesicle release. The protein is natively unfolded under physiological conditions, and is expressed predominantly in neural tissue. α-syn is associated with neuropathological conditions in Parkinson’s disease, where the protein mis...
Preprint
Full-text available
Excessive discharge of hazardous azo dyes into aquatic ecosystem is a global environmental concern. Here, we develop a green approach to remediate dye pollutions in water by fabricating an easy separable bio-nanocomposite, based on whey protein concentrate, its nanofibrils and montmorillonite nano-clay. Nanofibrils lead to a uniform dispersion of m...
Article
Nanotechnology-based approaches have shown promising potential to overcome the challenges associated with current therapeutic/diagnostic approaches and offer exciting solutions to improve the quality of life of Alzheimer's Disease (AD) patients. Unfortunately, thus far they have failed in clinical translation. These disappointing results question w...
Article
Full-text available
Interactions between proteins and surfactants are both of fundamental interest and relevant for applications in food, cosmetics and detergency. The anionic surfactant sodium dodecyl sulfate (SDS) denatures essentially all proteins. Denaturation typically involves a number of distinct steps where growing numbers of SDS molecules bind to the protein,...
Article
Correlative scanning probe microscopy of chemical identity, surface potential, and mechanical properties provides insight into structure‐functional relationships of nanomaterials. However, simultaneous measurement with comparable and high resolution is a challenge. Here, we seamlessly integrate nanoscale photothermal infrared imaging with Coulomb f...
Article
Full-text available
Many proteins have the potential to aggregate into amyloid fibrils, protein polymers associated with a wide range of human disorders such as Alzheimer’s and Parkinson’s disease. The thermodynamic stability of amyloid fibrils, in contrast to that of folded proteins, is not well understood: the balance between entropic and enthalpic terms, including...
Article
Force to be reckoned with: The correlations between nanoscale electrical, chemical, structural, and mechanical surface properties were explored in perovskite and amyloid fibrils with intrinsically integrated peak force infrared and Kelvin probe force microscopies. Correlative nanoimaging serves as a useful tool for deciphering the important underly...
Article
Full-text available
The α-synuclein (αSN) amyloid fibrillization process is known to be a crucial phenomenon associated with neuronal loss in various neurodegenerative diseases, most famously Parkinson's disease. The process involves different aggregated species and ultimately leads to formation of β-sheet rich fibrillar structures. Despite the essential role of αSN a...
Article
Transforming growth factor-β-induced protein (TGFBIp), an extracellular matrix protein, is the second most abundant protein in the corneal stroma. In this review, we summarize the current knowledge concerning the expression, molecular structure, binding partners, and functions of human TGFBIp. To date, 74 mutations in the transforming growth factor...
Article
Aggregation of α-synuclein (αSN) is an important histological feature of Parkinson disease. Recent studies showed that the release of misfolded αSN from human and rodent neurons is relevant to the progression and spread of αSN pathology. Little is known, however, about the mechanisms responsible for clearance of extracellular αSN. This study found...
Article
Protein aggregation to form amyloid is associated with many human diseases, increasing the need to develop inhibitors of this process. Here we evaluate the ability of derivatives of the small organic compound noscapine, derived from the opium poppy, to inhibit fibrillation of the model protein insulin. We combined biophysical methods to assess insu...
Article
Anionic surfactants denature proteins at low millimolar concentrations, yet little is known about the underlying molecular mechanisms. Here, we undertake 1-μs-long atomistic molecular dynamics simulations of the denaturation of acyl coenzyme A binding protein (ACBP) and compare our results with previously published and new experimental data. Since...
Chapter
Full-text available
Functional amyloid (FuBA) is produced by a large fraction of all bacterial species and represents a constructive use of the stable amyloid fold, in contrast to the pathological amyloid seen in neurodegenerative diseases. When assembled into amyloid, FuBA is unusually robust and withstands most chemicals including denaturants and SDS. Uses include s...
Article
While it is generally accepted that α‐synuclein oligomers (αSOs) play an important role in neurodegeneration in Parkinson’s Disease (PD), the basis for their cytotoxicity remains unclear. We have previously shown that docosahexaenoic acid (DHA) stabilizes αSOs against dissociation without compromising their ability to co‐localise with glutamatergic...
Article
Full-text available
Self-assembly of proteins to β-sheet rich amyloid fibrils is commonly observed in various neurodegenerative diseases. However, amyloid also occurs in the extracellular matrix of bacterial biofilm, which protects bacteria from environmental stress and antibiotics. Many Pseudomonas strains produce functional amyloid where the main component is the hi...
Article
Globular proteins are typically unfolded by SDS to form protein-decorated micelle-like structures. Several proteins have been shown subsequently to refold by addition of the nonionic surfactant octaethylene glycol monododecyl ether (C12E8). Thus SDS converts β-lactoglobulin, which has mainly β-sheet secondary structure, into a state rich in α-helic...
Conference Paper
Microorganisms can utilize functional amyloid in their extracellular matrix of biofilms to form robust biofilm resist mechanical and chemical stresses. Pseudomonas aeruginosa as an opportunistic pathogen that associated with chronic airway infections of cystic fibrosis patients use functional amyloids in its biofilm to mechanically strengthens the...
Article
Pseudomonas species export the amyloid-forming protein FapC to strengthen bacterial biofilm. P. species also produce the biosurfactant rhamnolipid (Rhl) and its outer membrane contains lipopolysaccharide (LPS). Given the possible contacts between FapC, Rhl and LPS, we here investigate how Rhl and LPS affect FapC fibrillation compared with SDS, know...
Article
This review article provides an overview of the different species that alpha‐synuclein (αSN) aggregates can populate. It also attempts to reconcile conflicting views regarding the cytotoxic roles of oligomers versus fibrils. αSN, while highly dynamic in the monomeric state, can access a large number of different assembly states. Depending on assemb...
Chapter
Extensive studies on the spontaneous collapse of phospholipid vesicles into supported lipid bilayers (SLBs) have led to procedures which allow SLB formation on a wealth of substrates and lipid compositions. SLBs provide a widely accepted and versatile model system which mimics the natural cell membrane separating the extracellular and intracellular...
Preprint
Full-text available
Many proteins have the potential to aggregate into amyloid fibrils, which are associated with a wide range of human disorders including Alzheimer's and Parkinson's disease. In contrast to that of folded proteins, the thermodynamic stability of amyloid fibrils is not well understood: specifically the balance between entropic and enthalpic terms, inc...
Article
Full-text available
Traditional approaches to achieve sustained delivery of pharmaceutical peptides traditionally use co-excipients (e.g., microspheres and hydrogels). Here, we investigate the release of an amyloidogenic glucagon analogue (3474) from an aggregated state and the influence of surfactants on this process. The formulation of peptide 3474 in dodecyl maltos...
Article
Full-text available
Aggregation of α-synuclein (αSN) is implicated in neuronal degeneration in Parkinson’s disease and has prompted searches for natural compounds inhibiting αSN aggregation and reducing its tendency to form toxic oligomers. Oil from the olive tree (Olea europaea L.) represents the main source of fat in the Mediterranean diet and contains variable leve...
Article
Full-text available
Biofilms are generated by bacteria, embedded in the formed extracellular matrix. The biofilm's function is to improve the survival of a bacterial colony through, for example, increased resistance to antibiotics or other environmental stresses. Proteins secreted by the bacteria act as a major structural component of this extracellular matrix, as the...
Article
Despite major advances in antibody discovery technologies, the successful development of monoclonal antibodies (mAbs) into effective therapeutic and diagnostic agents can often be impeded by developability liabilities, such as poor expression, low solubility, high viscosity and aggregation. Therefore, strategies to predict at the early phases of an...
Article
α-Synuclein (αSN) aggregation is central to the etiology of Parkinson's disease (PD). Large-scale screening of compounds to identify aggregation inhibitors is challenged by stochastic αSN aggregation and difficulties in detecting early-stage oligomers (αSOs). We developed a high-throughput screening assay combining SDS-stimulated αSN aggregation wi...
Article
Lipids often play an important role in the initial steps of fibrillation. The melanosomal protein Pmel17 forms amyloid in vivo and contains a highly amyloidogenic Repeat domain (RPT), important for melanin biosynthesis. RPT fibrillation is influenced by two lysolipids, the anionic lysophosphatidylglycerol (LPG) and zwitterionic lysophosphatidylchol...
Article
Full-text available
Purpose The peptide hormone glucagon, used to treat hypoglycaemic incidents, is prone to aggregation. Generating alternatives with better stability is of pharmaceutical interest in the treatment of diabetes. Here we investigate the impact of six different surfactants on the solubility and stability of ZP-GA-1, a stable version of glucagon. Methods...