Master Student (f/m/d)

General Description:

A Master’s thesis opportunity is available in the lab of Alexis Lomakin, Ph.D. (https://www.lomakinlab.org/), at the Center for Pathobiochemistry & Genetics, Medical University of Vienna, Austria. The thesis will be embedded in an ongoing research program investigating the fundamental mechanisms by which pathogenic cells living on or in the human body sense and adapt to stress. Cellular stress adaptation, particularly in the context of drug resistance in human cancer cells and opportunistic eukaryotic microbes, is an increasingly important global clinical challenge. Thanks to the advent of next-generation sequencing technologies and multi-omics approaches, we have learned a great deal about the molecular “parts lists” that cells reshuffle to survive under stress. Yet many pharmaceutical strategies designed to target these molecular-scale alterations ultimately fail, highlighting the need for a deeper understanding of cellular behavior under stress. One critical regulatory layer that remains largely hidden and overlooked in mainstream biomedical research is the subcellular spatiotemporal organization of biochemical reactions, which can change dramatically under stress. Given that form follows function, the overarching goal of our research is to discover how and why cells reorganize their subcellular architecture in response to stress, with particular emphasis on the nuclear domain, which we have found to be not merely a passive storage compartment for genomic DNA, but an active signaling and metabolic center of the cell.

Thesis Focus:

The primary focus of this thesis project will be to learn and establish a novel super-resolution optical microscopy technique: Expansion Microscopy / ExM (Chen, Tillberg & Boyden. Science, 2015; their step-by-step ExM “cookbook” protocol is available here: doi.org/10.1002/cpns.96). The goal will be to use this technique to resolve and quantitatively characterize a stress-induced subcellular phenotype we refer to as “bunch-of-grapes” nuclear domain organization. In this state, cells experiencing stress and error-prone mitoses package their duplicated genome into multiple (micro)nuclei that coexist within a shared cytoplasm. This unusual subcellular configuration provides an excellent model to address fundamental biological questions linking nuclear ploidy to cellular physiology in both homeostasis and stress, including:

- Do cells obey a strict one genome–one nucleus rule?

- What are the consequences of nuclear compartmentalization for the canonical flow of genetic information (DNA → RNA → protein)?

- How do cell signaling and metabolism adapt when multiple nuclei coexist in a shared cytoplasm?

- How does this configuration affect cell survival and stress tolerance?

We Offer:

- Training in quantitative cell biology, AI-assisted microscopy, and advanced bioimage informatics.

- Close supervision within an international and interdisciplinary research team.

- Access to state-of-the-art automated microscopy platforms, high-performance computing resources, and the lab’s intellectual infrastructure.

Candidate Profile:

- Strong practical experience in mammalian cell culture (experience in yeast microbiology is also welcome) and basic molecular biology techniques.

- Basic Python coding skills are desirable.

- Professionally mature, goal-oriented, highly motivated, and able to learn quickly and work independently.