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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. Building a living cell from scratch using microfluidics

Throughout the course of evolution life has developed a staggering complexity at the cellular level. To shed light on the fundamental blueprint of a cell and get a better understanding of the governing principles of cellular life, we are aiming to build a synthetic cell from the bottom-up using molecular building blocks (www.basyc.nl).

More specifically, we developed a microfluidic technology, Octanol-assisted Liposome Assembly (OLA), to produce cell-sized (5–20 µm) liposomes in our lab. These liposomes can be immobilized using microfluidic traps for further manipulations. In the past, we already succeeded in mimicking the form of rod-shaped bacteria by squeezing the liposomes into narrow confinements. Further, liposome growth was established by recruiting lipids from the external environment, and liposome division was induced by colliding them against well-defined microfluidic structures. Now the time has come to combine these modules into an integrated lab-on-a-chip system to establish a dynamic cycle of growing and dividing liposomes, mimicking a continuous life cycle of a living cell.

In this experimental and multidisciplinary project, you will gain experience working in a wetlab, learn how to operate a microfluidic setup, and perform basic light- and epifluorescence microscopy experiments. Based on these experiments we can further optimize parameters that are essential for the on-chip production of synthetic cells. If you are interested in this topic, please contact Bert Van Herck (B.VanHerck@[REMOVE THIS]tudelft.nl) for more information. Note that previous knowledge in biology or chemistry is helpful, but not necessary.


The controlled bubble-blowing process of Octanol-assisted Liposome Assembly (OLA), where monodispersed double-emulsion droplets are pinched off at the production junction to ultimately form unilamellar cell-sized liposomes.

2. Protein sequencing with nanopores

Nanopore technologies have been used by astronauts aboard the International Space Station and biologists travelling across the far reaches of the Earth to study DNA at the single-molecule level. However, analyzing the protein composition of cells at the single-molecule level, while an extremely valuable diagnostic tool, remains a difficult task. In this project we are taking important steps in developing nanopore technologies for proteomics.

Currently, we are exploring methods inspired by nanopore DNA sequencing. This approach involves attaching a small piece of protein (peptide) to a DNA strand to form a peptide-oligo conjugate (POC) which is pulled through a nanopore by a DNA motor enzyme. By measuring the ion current through the pore as the peptide moves through it, we can distinguish individual amino acids and detect important post-translational modifications! Our group has pioneered the proof-of-concept of this method, but engineering and data analysis breakthroughs are needed to push this technology to the next stage!

There is much to learn from this project, as it incorporates a multidisciplinary understanding of biology, biophysics, and biochemistry. You will gain experience working in a wet lab, learn how to handle datasets, and be involved in a very social lab environment. If you are a BEP/MEP/international student and interested to take part in this project, please contact Justas: j.ritmejeris[REMOVETHIS]tudelft.nl

We look forward to hearing from you!


3. Genome-in-a-Box: Bottom-up Reconstitution of Chromosome Organization

The molecular program of every cell is encoded in its genome. The genome size (the total number of DNA bases), varies over several orders of magnitude across organisms [1] (read more here). Despite this variety, all cells face the same critical challenge: to compact their genomes into the confined volume of a cell is a daunting task! Human cells have to compact about 1 m of DNA to 10 µm sized nucleus and bacteria about 1.4 mm of DNA to their micron sized nucleoids. How do cells do that? How do nanoscale proteins organize DNA into structures much larger then themselves? How does this influence the biophysical properties of DNA?

To contribute answers to these questions, we pursue the Genome-in-a-box project, where we isolate megabase-long DNA from live bacterium and combine it with purified proteins in microfluidic compartments which we then probe with fluorescent microscopy tools. This unique approach allows us to study the biophysics of large-scale chromosome organization, by analyzing the effects of individual DNA-organizing elements.

In context of this pursuit we have two open projects for either MEP or BEP students:

  • Characterization of size and dynamical properties of microfluidically confined chromosomes (including radius of gyration, mesh size, coefficient of diffusion, motion correlations and deformability) [2] (read more here).
  • Study of interaction of Structural Maintenance of Chromosome (SMC) proteins with isolated chromosomes [3] (read more here).

Both projects are experimental and will allow you to learn more about chromosome organization, DNA-protein interactions and microfluidics. Previous lab experience is helpful but not required. Do you find this interesting and want to learn more? Great! Please reach out to Martin Holub (m.holub[REMOVETHIS]tudelft.nl) or Alex Joesaar (a.h.joesaar[REMOVETHIS]tudelft.nl) and include a brief statement of motivation and description of your previous research experience in the email!



4. 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. Student projects are available as of April 2023.

The work involves sample preparation (working with lipids and proteins), fluorescence microscopy (spinning disc confocal) and Python-based image data analysis. The focus of a student project can be adapted according to your interests.

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


Figure: Min proteins forming a spiral pattern on a supported lipid bilayer. MinD-Cy3 in magenta, MinE-Cy5 in green.

5. 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.


6. 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

7. The ring of power – Building a biomimetic nuclear pore complex with DNA origami

The nuclear pore complex (NPC) is a huge, ring-shaped protein system inserted into the nuclear membrane that allows only certain macromolecules to translocate into the nucleus. It is an incredibly complex system that we aim to study using a bottom-up approach.

Our goal is to build a NPC from scratch by combining different NPC proteins (nucleoporins) grafted inside a ring-like DNA origami structure. 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 working with us, you will be directly involved in:

            •           Designing, folding and assembling DNA origami rings

            •           Protein functionalization of the DNA origami structure

            •           Analysis of the nanostructure + proteins via gel electrophoresis, mass photometry, fluorescence correlation spectroscopy

            •           Fluorescence microscopy and transmission electron microscopy

We are looking for enthusiastic Bachelor or Master students that are interested in trying to build life from the bottom up.

If you want to help us building the ring to rule them all, please contact Eva (e.bertosin@[REMOVE THIS]tudelft.nl) or Anders (a.barth@[REMOVE THIS]tudelft.nl)!