PhD Position in Retinal Aß and Tau Pathology

Catholic University of Leuven

Belgium

 
The Laboratory of Neuropathology led by Prof. Dr. Dietmar R. Thal is part of Department of Imaging & Pathology. The laboratory works together with other KULeuven research groups, VIB and external partners. The group in constantly growing and brings together PostDocs, PhD students, Master students and Lab technicians. The lab is interested in understanding the pathogenesis of Alzheimer's disease and related neurodegenerative disorders as well as in the validation of novel AD biomarkers, e.g. amyloid PET or the eye as a biomarker.

Project

Alzheimer’s disease (AD) is the most frequent neurodegenerative disorder leading to dementia. Amyloid β-protein (Aβ) and abnormal phosphorylated τ-protein (p-τ) are the pathological hallmark proteins. Recently, Aβ and p-τ aggregates were found in the retina of AD patients. It not yet clear when in the pathogenesis of AD retinal lesions occur or whether p-τ lesions can also be related to other degenerative diseases in the retina such as in the brain. Here, we hypothesize that there is a specific AD-related pattern of Aβand p- τpathology in the retina and that this pathology can start in non-demented individuals in preclinical AD. Accordingly, our 1st objective is to analyze age distribution and topographical patterns of retinal Aβand p-τ pathology in elderly individuals and AD patients. This is important since imaging techniques focusing on the detection of retinal Aβ are currently tested as possible biomarkers for AD.

Recently, we have shown in amyloid precursor protein (APP)xτ-transgenic mice that Aβ accelerates p-τ pathology in the brain via a link of both proteins to prion protein (PrP). Similar interactions of Aβ and p-τ with PrP were seen in AD patients. Whether a similar link can also be observed in the retina is not clear. Based on our results in the brains of APPxτ transgenic mice we hypothesize that Aβ can accelerate retinal p-τ pathology via interactions with PrP. Thus, the 2nd objective is to determine cooperative effects between Aβand p-τ
in the retina, presumably indicative for an AD-related pathogenetic mechanism.

Spreading is currently considered as an important mechanism explaining the expansion of p-τ and Aβ pathology from one brain region into others. This leads to the hypothesis that p-τ and/or Aβ aggregates in the retina lead to a spreading of the respective protein aggregates into the brain. Accordingly, our 3rd objective is to test whether the retina is involved in AD-like spreading of Aβ and p-τaggregates.

By addressing these objectives, we will be able to clarify whether there is a specific AD-related pattern of retinal Aβ and p-τ pathology, whether these pathologies start already in preclinical AD, and whether the presence of ADrelated pathomechanisms (cooperation of Aβ and p-τ, spreading) in the retina confirms a possible involvement of the retina in AD.

We want to determine the prevalence and topographical pattern of Aβ and p-τ pathology in the retina of elderly individuals and AD patients using immunohistochemistry.

Immunohistochemical and biochemical analysis will allow us to clarify whether APPxτ-transgenic mice will have more p-τ and /or Aβ pathology than the respective single transgenic mice. We want to test whether Aβ and p-τ seeds injected into the subretinal zone induce or accelerate Aβ or p-τ pathology in the brain regions to which the optic nerve projects.
 
Responsibilities  

• You will do animal experiments with transgenic mice (eye injections).
• You will do Immunohistochemical and imunofluorescence stainings and analysis of human and mouse eyes samples. 
• You will pathologically analyze mouse and human eyes.
• You will supervise lab rotation students and master students.
• International exchange in the course of the project is considered.
• You will report your data to your supervisors, other researchers, as well at (international) conferences.

Profile

The candidate should be experienced in the following techniques:
• Immunohistochemistry, immunofluorescence
• microscopy
• sample preparation for biochemical analysis
• SDS-PAGE
• western blot analysis
• PCR analysis
• working with lab animals
 
What we are looking for:
• You have a Master degree according to EU standards
• You meet the English language criteria of KU Leuven
• You have FELASA B certificate for carrying out animal experiments (if not we expect that you follow the FELASA B course within the first 3 months)
• You are willing to work with patient tissue and conduct animal experiments
• Highly motivated, enthusiastic, critical and creative
• You have the ability to work in a team 
• You are willing to participate in an international exchange program for one year of the PhD.

Offer

• PhD-Student position for 4 year (financed by Stichting Alzheimer Onderzoek (3 years))
• Promotion of your PhD-thesis to be written within the four years
• Participation in an individually shaped PhD-Program
• Presentation of valuable findings at international conferences
 
You will be working on a hot topic in Alzheimer’s disease research, in a leading lab with a widespread network of international and local collaborators, and in an excellent research environment at KU Leuven.
Starting date: as soon as possible.

Interested?

For more information please contact Prof. dr. Dietmar Thal, tel.: +32 16 34 40 47, mail: dietmar.thal@kuleuven.be or Mrs. Alicja Ronisz, tel.: +32 16 37 67 82, mail: alicja.ronisz@kuleuven.be. Please complete the online application procedure and include a detailed CV including list of publications and a motivation letter.

You can apply for this job no later than January 21, 2021 via the
KU Leuven seeks to foster an environment where all talents can flourish, regardless of gender, age, cultural background, nationality or impairments. If you have any questions relating to accessibility or support, please contact us at diversiteit.HR@kuleuven.be.
  • Employment percentage: Voltijds
  • Location: Leuven
  • Apply before: January 21, 2021
  • Tags: Neurowetenschappen


In your application, please refer to Professorpositions.com

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