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Student projects

We welcome students from a variety of backgrounds to participate in our research. Our group currently has the following opportunities for carrying out a bachelors or masters research project.

1. Improving our understanding of biological pattern formation

The Min protein system famously determines the cell division plane in E. coli bacteria. To this date, it remains the best-studied model system for intracellular pattern formation. However, lots of details on the inner workings of this system remain unclear. We work with reconstituted Min proteins in vitro to study their behavior, aiming to improve our understanding of biological pattern formation. New projects are currently in planning. Student (BEP) project will become available as of March 2022. International students welcome!

The work involves sample preparation, fluorescence microscopy and image analysis.

Interested? Please contact Sabrina Meindlhumer (PhD student), s.meindlhumer[REMOVE THIS]tudelft.nl for more information!


In Figure: Min proteins forming a spiral pattern on a lipid bilayer

2. AFM-Fluorescence characterization of the plasmid partition protein ParB

A plasmid is a small, up to 2×105 pairs of bases, circular DNA molecule found inside various living organisms. The genes codified in these molecules are not essential as those codified in chromosomes, but provide some benefit for the cell (e.g. antibiotic resistance), hence, the importance of the cellular mechanisms responsible for the maintenance and organization of these molecules and their role in evolution.
ParB is a DNA-binding protein. The binding to DNA and polymerization of several ParB proteins could be associated with DNA condensation during cellular division, however, the specific recognition of a sequence and its utility to this mechanism remains a challenge for the scientific comunity.
In this project, the binding to and recognition of a specific sequence on a DNA molecule by ParB are studied using Fluorescence and Atomic-Force Microscopy. The outcome of this research project will improve our understanding of ParB’s binding mechanism to DNA.
For more information, contact Alejandro Martin (a.martingonzalez@tudelft.nl)
“Because all of biology is connected, one can often make a breakthrough with an organism that exaggerates a particular phenomenon, and later explore the generality.” – Thomas Cech, chemistry Nobel laureate 1989.


3. Shining Light on the Nuclear Pore Complex using a Zero-Mode Waveguide

Selective transport of the Nuclear Pore Complex (NPC) can be reconstituted in minimalistic systems that consist of a solid-state nanopore functionalized with FG-nucleoporins. However, such systems present limitations in terms of biological relevance (due to applied electric field), and scalability to investigate more complex scenarios.

In this project, we tackle all these issues by with a method based on Zero-Mode waveguides (ZMW), sub-wavelength apertures in metal films (Fig.1), which we engineer with FG-nucleoporins. Even though light can not pass through the metal layer, molecules can still diffuse through the small aperture. As they reach the other side, fluorescent molecules are illuminated by the laser, one by one, resulting in single spikes in the detected signal.

With this technique we can for the first time study:
–       Selective transport at the single-molecule level in free diffusion (no applied electric field)
–       Parallel detection and discrimination of two, or more, proteins that translocate simultaneously
This approach will yield new mechanistic insights about transport through the real nuclear pore complex.

During this inter-disciplinary project you will learn how to work with ZMWs and operating a high end microscope, in order to do single molecule fluorescence experiments. Additionally, you will gather experience in
handling biological samples, functionalizing  ZMWs with purified proteins, protein labelling, and learn about the nuclear pore complex.

If this triggers you, please contact Nils Klughammer (n.klughammer@[REMOVE THIS]tudelft.nl).


Figure 1: Zero-Mode Waveguide


Compartimentalization of DNA in the nucleus is one of the central features that distinguishes eukaryotic cells from simpler organisms. Like a door connecting two rooms, a huge multiprotein complex, the nuclear pore complex (NPC), enables communication and controlled passage of molecules between the nucleus and the cytoplasm. Fundamental cellular functions, like protein production, require the messenger molecule RNA to exit the nucleus through the NPC door; yet, how this transport actually occurs is still unclear.
The final goal of the mRNA NEXT project is to recreate a minimal nuclear export system that is able to drive transport of RNA in a functional mimicking of NPC. Recreating the functionality of the NPC de novo will allow us to unravel the nature of the minimal transport complex.

We use a current-base reading that enables us to distinguish single transport events of proteins and RNA through the biomimetic NPC. Since the proteins involved perform other tasks in the cell, our unique bottom-up approach is vital to address these questions. By joining this project, you will contribute to the first-ever successful reconstruction of mRNA export in a completely in vitro system!

You will be directly involved in experimental design, trained on protein production, molecular biology techniques, single molecule nanopore technology and QCM-D, in a unique combination of interdisciplinary methods at the merge of cell biology, biochemistry and bioengineering.

We are looking for independent and enthusiast Master/Bachelor students with Physics, Biology, or interdisciplinary background. International students are especially encouraged to apply.

For more info, contact Paola De Magistris (P.Demagistris@[REMOVE THIS]tudelft.nl) or visit our labs in Applied Sciences (office 58.F0.150).


5. Building a biomimetic nuclear pore complex with DNA origami

DNA origami nanotechnology has enabled us to design and build specific shapes and structures on the nanoscale. We use this approach to build a minimalistic version of the nuclear pore complex (NPC) by grafting the disordered proteins of its central channel to the insides of a hollow octagonal DNA origami with a diameter of 35 nm. This approach gives us precise control over the stoichiometry and the positioning of individual proteins. We utilize this platform to study the arrangement and structural dynamics of the FG-nucleoporins in the pore on the single-molecule level by a variety of methods, including TEM, AFM, mass photometry and single-molecule FRET.

We are looking for enthusiastic Bachelor or Master students that are interested in trying to build life from the bottom up. During the project, you will learn how to build a biomimetic nuclear pore complex, validate the correct assembly, and characterize its properties using state-of-the-art single molecule methods.

If you are interested in this challenging, interdisciplinary project, please contact Anders Barth at a.barth@[REMOVE THIS]tudelft.nl.


6. Mimicking selectivity of the Nuclear Pore Complex with Designer FG-Nups

In this project, we attempt at reconstituting NPC selective transport in biomimetic nanopores using bottom-up designed artificial FG-Nups. By testing the impact of systematic variations of artificial FG-Nups on selectivity, we aim at unraveling what are the minimal features for having an efficient and selective transport. We believe this novel approach will finally shed light on some fundamental physical principles that govern the NPC behavior. 

We are looking for an enthusiastic Master/Bachelor student with a multidisciplinary background or interest. Depending on the duration of your project, you will get trained on engineering nanopores with FG-Nups, testing selective behavior of biomimetic NPCs and processing data (Matlab). Besides, you will get hands-on experience in using a TEM machine and detecting protein binding with a QCM-D.

If you feel thrilled, please contact Alessio at A.fragasso@[REMOVE THIS]tudelft.nl or drop by office (F0.170).