Throwing light on Parkinson's and Alzheimer’s disease...

To begin with

Scientists invent fluorescent dyes with improved properties that can be effectively used in early diagnosis of Parkinson’s and Alzheimer’s disease.

Keywords

Fluorescence, Parkinson’s disease, Alzheimer’s disease, Molecular carrier, Fluorescent dye, Hydrophobic

About

Fluorescent dyes (or labels) are fluorescent molecules used in medical samples to detect and visualize various biological structures. (watch Garima Ghale showing how fluorescenct dyes work) Most fluorescent labels are by nature hydrophobic (i.e. they do not mix with water) and they get attracted by hydrophobic surfaces. As a result, they accumulate in the hydrophobic area of interest allowing its visualization.
The research group led by Prof. Werner Nau at Jacobs University Bremen has successfully used the fluorescent labels thioflavin T and congo red to visualize insoluble (hydrophobic) plaques of amyloid proteins found in the brains of Parkinson’s and Alzheimer’s disease patients. (watch Roy D'Souza talking about amyloid plagues)
The researchers team currently works on improving the properties of fluorescent dyes by placing them in special molecular carriers -also called biomimetic macrocyclic containers. (watch Prof. Nau talking about the research project)

Links with society

The research of the group led by Prof. Werner Nau at Jacobs University Bremen is conducted at the interface of two scientific fields, the photochemistry and the supramolecular chemistry. It aims to enhance the fluorescent characteristics of the dyes for medicinal and industrial applications. (watch Prof. Nau talking about the innovative character of the project) Fluorescent molecules (or dyes) can support the diagnosis of medical conditions such as Parkinson’s and Alzheimer’s disease. Improving the fluorescent properties of the dyes is very important for the early-stage detection of the Parkinson’s and Alzheimer’s diseases, which is presently possible only post-mortem. Dyes with improved fluorescent properties are in high demand in various technological applications such as fluorescence microscopy, dye lasers, drug delivery, information storage, trace element detection and bioassays. (watch Prof. Nau giving another example of application of fluorescence in medicine)
An everyday application of fluorescent dyes can be found in clothing. High visibility cloths, which are very popular among young people, contain fluorescent dyes that intensify the colours and make them more attractive.  (watch Amir Norouzy talking about fluorescence) This type of clothing is mainly used as protective work-safety equipment, which is easily distinguished from the background. High visibility cloths are made of fluorescent materials with added reflective tapes or shapes. The fluorescent colours increase the daytime visibility, while the reflective tapes the night time visibility. (watch Prof. Nau explaining fluorescence in the molecular level)

Research innovation

The research group led by Prof. Werner Nau at Jacobs University Bremen studies large molecular carriers (called 'biomimetic macrocyclic containers') that are able to mimic quite well the microenvironment provided by aggregated biological substances. (watch Prof. Nau talking about biomimetic systems)
In the case of Parkinson’s and Alzheimer's disease, the substances of biological interest are the amyloid proteins, which are usually found in the form of insoluble (hydrophobic) plaques around the affected neurons. This property of the biomimetic containers enable the scientists to study, test and improve the qualities of various chemicals in simpler systems in the lab before applying them to real biological environments. (watch Vanya Uzunova talking about the research innovation)

Relevant scientific publications:

1) A. Hennig, H. Bakirci, W. M. Nau, “Label-Free Continuous Enzyme Assays with Macrocycle-Fluorescent Dye Complexes”, Nature Methods 2007, 4, 629-632.


2) N. Saleh, A. L. Koner, W. M. Nau, “Activation and Stabilization of Drugs by Supramolecular pKa Shifts: Drug Delivery Applications Tailored for Cucurbiturils”, Angew. Chem. Int. Ed. 2008, 47, 5398–5401.


3) W. M. Nau, “Supramolecular Capsules: Under Control”, Nature Chemistry 2010, 2, 248-250.

Description of the method

The research methodology followed by the group of scientists led by Prof. Werner Nau at Jacobs University Bremen is built in three steps:

Step 1
The scientists identify favourable interactions between certain molecular carriers (also called 'biomimetic macrocyclic containers') and the fluorescent molecules of interest. In effect, they try to match hosts and dyes from a vast variety of such molecules.

Step 2
With the help of optical spectroscopy they identify a host-dye system focusing on its properties, i.e. strong binding, spectral change, increased brightness, and better solubility. (watch Alexandra Irina Lazar talking about property changes in the host-dye system)

Step 3
They introduce biomolecules (e.g. proteins) into the system in order to visualize biological samples and track their location in cells and tissues.

This method also allows monitoring how chemical processes evolve over time. (watch Mara Florea talking about how they monitor enzymatic conversion) The scientists can measure small changes in the substance concentration in a solution, which correspond to changes in the fluorescence intensity of the interacting host-dye system. (watch Roy D'Souza talking about the research steps)

Historical background

The biomimetic containers used in research projects conducted by the Jacobs University Bremen team, are part of the field of Chemistry called Supramolecular Chemistry. Supramolecular Chemistry became widely recognized with the 1987 Nobel Prize in Chemistry, which was awarded to Donald J. Cram, Jean-Marie Lehn and Charles J. Pedersen for their contributions in the field. Their discovery described the use of artificial molecules (hosts), which can mimic or function as biological receptors and selectively recognize their analytes (guests). Nowadays, research groups all over the world are using supramolecular concepts to improve the properties of their systems without employing real chemical modifications.

The “face” of Science: Let’s meet the scientists!

Let’s meet the scientists!

The research group led by Prof. Werner Nau at Jacobs University Bremen works on improving the properties of fluorescent dyes, which will eventually help in early diagnosis of Parkinson’s and Alzheimer’s disease. But, who are these people working behind the scenes?

The “face” of science:  Dr. Werner Nau, Professor of Chemistry at Jacobs University Bremen (Germany)

Brief Introduction: I am a full professor of chemistry at Jacobs University Bremen since 2002. I am currently in charge of a research group working in the fields of photochemistry and supramolecular chemistry. I have studied in Germany and Canada, and I have held research and teaching positions in Switzerland, Canada, the USA, and the UK.

Research Interests: Development of new applications of fluorescent probes in supramolecular chemistry and biochemistry by combining organic synthesis of dyes and macrocyclic hosts with photophysical characterization.

Sources of inspiration: I am often inspired from simple everyday events. Sometimes a discussion with a colleague or a co-worker may stimulate thinking in research activities. I usually like to try the unconventional in my research.

Important moments in his “scientific life”: The development of molecular ‘spies’ to monitor the progress of complex reactions, both accurately and affordably.

Research team behind the scenes:
I am working with a team of inspiring colleagues, which is comprised of students and scientists from seven different nationalities. (watch here videos of the research team) They participate in diverse projects involving different methods to investigate fluorescent dyes and their interactions with biomimetic containers. Our team also collaborates with different research groups around the world. We take part in joint projects with scientists from Germany, UK, Spain, Romania, Israel, Jordan, Iran, India and China.

Scientific editor of the Digital Exhibit: Roy D’Souza, graduate student at Jacobs University Bremen (Germany)

"During high school I was more interested in computer science and engineering, but in university I discovered that chemistry was the only subject that I thoroughly enjoyed studying. I am glad that I participate in professor Nau workgroup, where the diverse areas of research investigated are particularly stimulating. I am currently involved in developing simulation models for our research in enzymatic assays as well as peptide dynamics. Studying reaction catalysis as well as chemical switching has also been part of my previous research."

Scientific editor of the Digital Exhibit: Vanya Uzunova , graduate student at Jacobs University Bremen (Germany)
"I decided to study chemistry because I have always been interested in the ingredients of everyday-use products: small molecules, which help in getting over acid stomach, stop your knee pain, curl your hair better… Chemistry provides the explanation about how these molecules work as well as the tools for their improvement. The research in professor Nau workgroup focus on enhancing the properties of fluorescent molecules, which eventually leads in solving real-life issues. Moreover, participating in this group is an enjoyable and unique experience for me."

Editing Team

Editing team for the Digital Exhibit "Throwing light on Parkinson's and Alzheimer's disease..."

Scientific editors: Prof. Werner Nau Roy (leader of this research project); Roy D’Souza, graduate student at Jacobs University Bremen; Vanya Uzunova , graduate student at Jacobs University Bremen 


Content Coordination: Glykeria Anyfandi
Science Communication Editors: Evlalia Amygdalaki, Glykeria Anyfandi
Content Administration: Christina Troumpetari, John Stoitsis
Technical Development: John Stoitsis
Photographs, videos & web material: Evlalia Amygdalaki
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