Project

MOLECULAR CAUSES OF ALZHEIMER'S DISEASE: FROM PROTEIN TO PATIENT

Publisher

Supervisor

Location

Greater Copenhagen area

What causes Alzheimer's and how do we find a cure? This project aims to pinpoint underlying molecular causes of Alzheimer's Disease by direct coupling of clinical data for patients suffering from genetic forms of the disease with the chemical properties of the protein mutants that these patients carry.

This coupling is a unique technique developed by our research group at DTU which has led to a range of recent breakthroughs in the understanding of the disease in 2015 and 2016 (1,2,3,4).

Alzheimer’s Disease is a devastating neurodegenerative disease and one of the major challenges of this century, with millions of people affected world-wide and prevalence growing steadily (5,6,7).

The specific objectives of this project are 1) to construct a major database of Alzheimer’s Disease including both clinical data (survival times, age of diagnosis/onset) for patients who have inherited Alzheimer's and the associated chemical properties of the corresponding protein variants; 2) show that statistically significant correlations exist between these two types of data; 3) identify the protein properties that correlate with disease. These properties can then be used to develop biomarkers for early-stage diagnosis and in future drug discovery programs directed towards treating this terrible neuro-degenerative disease.

The project involves a range of bioinformatics tools, physical chemistry and computational chemistry techniques and can vary in difficulty from undergraduate and bachelor students, to master student level.

 

(1) Somavarapu, A. K.; Kepp, K. P. The Dynamic Mechanism of Presenilin-1 Function: Sensitive Gate Dynamics and Loop  Unplugging Control Protein Access. Neurobiol. Dis. 2016, 89, 147–156.

(2) Somavarapu, A. K.; Kepp, K. P. Loss of Stability and Hydrophobicity of Presenilin 1 Mutations Causing Alzheimer’s Disease. J. Neurochem. 2016.

(3) Tiwari, M. K.; Kepp, K. P. β-Amyloid Pathogenesis: Chemical Properties versus Cellular Levels. Alzheimer’s Dement. J. Alzheimer's Assoc. 2016, 12 (2), 184–194.

(4) Somavarapu, A. K.; Kepp, K. P. Direct Correlation of Cell Toxicity to Conformational Ensembles of Genetic Abeta Variants. ACS Chem. Neurosci. 2015, 6, 1990–1996.

(5) Goedert, M.; Spillantini, M. G. A Century of Alzheimer’s Disease. Science 2006, 314 (2006), 777–781.

(6) Kepp, K. P. Bioinorganic Chemistry of Alzheimer’s Disease. Chem. Rev. 2012, 112 (10), 5193–5239.

(7) Kepp, K. P. Alzheimer’s Disease due to Loss of Function: A New Synthesis of the Available Data. Prog. Neurobiol. 2016, 143, 36–60.


In collaboration with

Mulige virksomhedspartnere

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Contact

Company / Organization

DTU Kemi

Name

Kasper Planeta Kepp

Position

Professor

Mail

kpj@kemi.dtu.dk

Supervisor info

MSc Eng in Applied Chemistry

Supervisor

Kasper Planeta Kepp

ECTS credits

5 - 30

Type

BSc project, MSc thesis, Special course

Technical University of Denmark

For almost two centuries DTU, Technical University of Denmark, has been dedicated to fulfilling the vision of H.C. Ørsted – the father of electromagnetism – who founded the university in 1829 to develop and create value using the natural sciences and the technical sciences to benefit society.


Today, DTU is ranked as one of the foremost technical universities in Europe, continues to set new records in the number of publications, and persistently increases and develops our partnerships with industry, and assignments accomplished by DTU’s public sector consultancy.

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