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Project Overview

Project Code: MH 13

Project name:

High-content screening of small molecule compounds in autophagy-deficient cell types

TUM Department:

MH - Medicine

TUM Chair / Institute:

Institute of Human Genetics

Research area:

Therapeutic approaches in pre-clinical models of NBIA

Student background:

BiologyMedicine

Further disciplines:

Participation also possible online only:

Planned project location:

Ingolstädter Landstraße 1
85764 Neuherberg
Germany

Project Supervisor - Contact Details


Title:

Dr.

Given name:

Arcangela

Family name:

Iuso

E-mail:

arcangela.iuso@helmholtz-munich.de

Phone:

 +49-89-3187-43149

Additional Project Supervisor - Contact Details


Title:

Given name:

Family name:

E-mail:

Phone:

Additional Project Supervisor - Contact Details


Title:

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Project Description


Project description:

Title:
Testing Autophagy-Restoring Compounds in Patient-Derived Fibroblasts Using High-Content Imaging

Project Summary:
Autophagy dysfunction contributes to the pathogenesis of several neurodegenerative and lysosomal storage disorders. In this project, we will use an established high-content imaging (HCI) platform to test candidate compounds for their ability to restore autophagy function in patient-derived fibroblasts carrying known mutations in autophagy-related genes.

Using quantitative imaging of key autophagy markers—including LC3 (autophagosome formation), p62/SQSTM1 (cargo clearance), and lysosomal markers (e.g., LAMP1, LysoTracker)—we will assess autophagic flux in response to pharmacological treatment. Fibroblasts will be treated with selected compounds known or predicted to modulate autophagy pathways (e.g., mTOR inhibitors, TFEB activators, AMPK modulators), under both basal and stress-induced conditions.

Key Objectives:

To evaluate the effect of candidate compounds on autophagosome formation and cargo degradation in autophagy-defective fibroblasts.
To compare treatment responses between mutant and control fibroblasts using quantitative image-based metrics.
To identify compounds that significantly rescue autophagy phenotypes, based on reduction of p62 accumulation, increased LC3 puncta turnover, and improved lysosomal function.
Expected Outcomes:
This project will identify promising autophagy-restoring compounds suitable for further preclinical development. It will also generate quantitative phenotypic data that can be used for mechanistic follow-up and to support future high-throughput compound screening in patient-derived cell models.

Working hours per week planned:

40

Prerequisites


Required study level minimum (at time of TUM PREP project start):

2 years of bachelor studies completed

Subject related:

Basic Cell Biology Knowledge; Laboratory Experience in Cell Culture (Aseptic technique, Maintenance and passaging of adherent cell lines); Familiarity with staining techniques and imaging fixed cells; Data Handling and Documentation Skills

Other:

Recommended (But Can Be Taught During the Project)
Immunofluorescence Staining; Experience with staining intracellular proteins (e.g., LC3, p62, LAMP1);
Image Analysis Basics (ImageJ/Fiji)

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