Project Examples, StemPhys & Optical Tweezers

The following are master's project examples, meant to be inspirational. Inquire directly with the supervisor to find a project of interest to you and of use to the project.

Some of the projects may also be suited to bachelor projects. 

Exploring the physical connection between membranes

The goal of this master’s project is to study the physical interaction between the endoplasmic reticulum (ER) and the plasma membrane (PM) and interaction which is critical for calcium uptake in cells and hence their viability. This occurs through the two membrane proteins STIM1 and ORAI1.

Exploring the physical connection between membranesWe are interested in how the ER-PM interaction is formed and which conditions can stimulate it. We will explore the role of STIM1/ORAI1 redistribution and complex formation under conditions of stress, such as calcium depletion of the Endoplasmic Reticulum and by extraction of the cell membrane with an optical tweezer. We are in the Optical Tweezers lab working with local heating as cancer treatment and we seek to understand molecular responses in cells exposed to localized heating. This approach will therefore tie this project to some of the overall interests of the lab.

Key Questions:

  1. Will the endoplasmic reticulum follow the plasma membrane into the membrane tube which forms when pulling the plasma membrane with optical tweezers?
  2. Does #1 change with induction of ER-PM interaction by ER calcium depletion or other stimuli? Can we modify the intermembrane interaction by calcium depletion or other stimuli?
  3. Does the distribution of STIM1 protein respond to local heating of the cell?

Main Techniques: Confocal microscopy, Laser trapping of beads with Optical Tweezers, plasmonic heating, Cell cultures and transfections and membrane related techniques, cell accelerator. Data analysis using e.g. ImageJ or Matlab.

Supervisors: Poul Martin Bendix,
Benedicte M. Pers,

Membrane properties of lean and obese hepatocytes

Membrane properties of lean and obese hepatocytesIn progressive obesity, excess energy is stored in organs and cells not made for lipid storage, such as muscle and liver. This accumulation of lipids presents the cells with a huge burden, which in many cases has been associated with insulin resistance and type-2-diabetes. Lipid droplet in liver cells take up physical space in the cells and comprise cellular function.

In this project, the goal is to understand the biophysical properties of liver cells, especially in the physiological condition of obesity. Thousands of cells can be analyzed in minutes to reveal physical differences between cells from lean or obese animals by using a newly developed tool called the Cell Accelerator. Additionally, single cells can be chosen for microscopic investigation of the physical environment of the cell using optical tools.

We will assess different cellular parameters and ultimately compare these observations between liver cells from lean and obese animals. This type of measurements has not yet been performed and established for liver cells, and can contain information critical for our understanding of cellular dysfunction in disease. 

Key Questions:

  1. What is the strength of the actin cortex in liver cells?
  2. The biophysical properties we will explore are: strength of the actin cortex. membrane stiffness, tracking of granulus inside the cells. 
  3. We will simulate obesity by loading cell lines (hepa1-6 or Hek293t cells) with a lipid mixture, which will induce a large amount of lipid uptake in short time.
  4. To work with the physiological condition of obesity, we will isolate primary hepatocytes and perform the above experiments on these cells.

Main Techniques: Confocal microscopy, Laser trapping of beads with Optical Tweezers, Cell accelerator, Cell cultures and transfections and membrane related techniques. Data analysis using e.g. ImageJ or Matlab. Animal experiments will be performed at Panum.

Supervisors: Poul Martin Bendix,
Benedicte M. Pers,

Membrane Dynamics: Isolation of plasma membranes for studying the dynamics of proteins

Are you interested in understanding the mechanisms behind:

  •  diffusion of proteins and lipids in membranes
  •  how membranes are shaped by proteins
  •  how membrane curvature affects distribution of proteins
  •  how cancer cells repair their membranes to facilitate invasion
  •  how cancer cells and stem cells interact with their surroundings via filopodia

then you are welcome to contact me for discussing a master's project within these topics.

Membrane Dynamics: Isolation of plasma membranes for studying the dynamics of proteins

Main Instruments: Confocal microscopy, Micromanipulation, Optical Tweezers, Plasmonic heating of nanoparticles, Cell cultures and transfections and membrane related techniques. Data analysis using e.g. ImageJ or Matlab.

Projects will involve collaborations with: Danish Cancer Research Society Center (DCRSC) and Stockholm University

Supervisor: Poul Martin Bendix,

Alternative insulin delivery

Alternative insulin deliveryThis project takes place mainly at Novo Nordisk, Hillerød at the Alternative Delivery department which lies in the intersection between medical device engineering and drug discovery and research. A core focus lies within alternative drug delivery technologies that can alleviate the need for frequent injections for diabetic patients. Examples of technologies in scope include oral devices, implants, and transdermal patches. Beyond drug delivery, the group explores implant devices to enable novel stem cell-based therapeutics. Concerning type 1 diabetes, a special focus is on pursuing a cure based on stem cells with the goal of developing an implantable device that can encapsulate these cells and ensure their functionality, while protecting them from the patient’s immune system.

Supervisors: Peter Herskind (Novo Nordisk) / Lene Oddershede (NBI),

Analytical rheology of viscoelastic materials for insulin delivery

This project takes place mainly at Novo Nordisk, Hillerød, with the overall goal of investigating the biophysical characteristics of the polymer materials inside the Novo Nordisk pen devices. The project can be either experimental or theoretical of nature, depending on the background and interests of the candidate and may involve the following:

  • Development of experimental methods for Dynamic Mechanical Analysis (DMA) of polymer materials.
  • Use of DMA in studies of polymer materials currently used in medical devices e.g. crosslinked and thermoplastic elastomers.
  • Rheology and micro-rheological measurements.
  • Development of mathematical models to aid the interpretation of DMA data in order to elucidate structure-property relations.

Methods: DMA, possibly optical tweezers, modeling.

Supervisors: Jesper Bøgelund (Novo Nordisk), Lene Oddershede (NBI),

War of species

Picture of topoligical defectsSpatial spreading is the most important mechanism for species to become very abundant, whether we are considering bird flocks, fungi, plants, or bacterial colonies on agar. On a surface, bacteria will align along the surface and, most often along the same axis, i.e., like rods in a box. The parallel alignment of cells is explained by cells competing for space that push against each other, and this mechanical instability leads to buckling and folding of the cell line along the surface. Hence, cell divisions in compact monolayers gives rise to topological defects as known from, e.g., liquid crystals or fingerprints.

You will investigate how different species meet and compete on a surface and, in particular, how this affects the patterning of the interface. The main aim of the project is to give a precise description of the topology of meeting fronts and the exploration of a stochastic model that includes both growth and motility. Hence, with this simple bacterial model, we can point out general features and draw parallels to mammalian cells, where migration of multicellular groups is indispensable for wound healing, embryonic development, and the infiltrative histopathology of cancer.

This project is the result of a collaboration with the University of Oxford and includes bacterial cell culture, fluorescence microscopy, and image analysis. 

Supervisor: Liselotte Jauffred,

Brain tumors in a jar

Glioblastoma multiforme tumors form in brains’ white matter and remains one of the most lethal cancers, despite intensive therapy and surgery. The poor prognosis is the result of therapeutic resistance and infiltrative growth into the surrounding brain matter. Thus, there is an urgent need for exploring new treatment strategies as, e.g., nanoparticle-based photothermal therapy (see Tumor elimination).

Brain tumorWe offer various projects to explore possible therapeutic strategies:

  • Development of miniature brain tumors models in petri dishes.
  • Quantification of therapeutic effect on motility, proliferation, and necrosis/apoptosis and of (side) effect on normal human astrocytes.
  • Coating of nanoparticles for homing/targeting of tumors.

You will treat miniature brain tumors in petri dishes to measure the therapeutic effect on motility, proliferation, and necrosis/apoptosis and compare to the (side) effect on normal human astrocytes.

This project is the result of a collaboration with the Danish Cancer Research Institute and can include mammalian cell culture, advanced fluorescence microscopy, and image analysis. 

Supervisors: Liselotte Jauffred, Henrik Klingberg, and Lene Oddershede,

Patterning in large cell communities

We have most of our knowledge about microbes from liquid cultures, where bacteria
are freely swimming entities in a flask. However, in nature bacteria actively
search for a surface to form larger communities, i.e., biofilm, with extended
cooperativity and defense. When such newly-founded populations expand, the
first individuals to arrive in a new territory are likely to be the ancestors
of the later populations in this area. Hence, sectors with low genetic diversity
are formed within the colony, even among cells of similar fitness. This
self-organization of microbial cell communities is the result of genetic drift
in complex interplay with evolution, competition, and cooperation.

We offer various projects to explore pattern formation by growing bacteria both in vivo and in silico. We believe the close interplay between theory and experiments will provide a more complete understanding of cooperation and competition among cells in larger communities.  We aim to point out general features of growth pattern, which can be generalized in wider class of systems. In the long term, we may draw parallels to mammalian cell systems, where patterning is crucial for example in embryonic development.

Possible subprojects include:

  • Understanding the chirality of the sector boundaries observed in experiments
  • Colony growth in quasi-2-dimension vs. 3-dimension
  • The relation between the cell shape of individual cells and the colony shape

This project combines theory and experiments depending on your interests. Experimentally, the project can include bacterial cell culture, colony growth, and advanced fluorescence microscopy. Theoretically, we plan to first simulate an individual cell-based model where the particles grow, divide, and interact through mechanical force. Depending on the development of the project, simplified lattice models or partial differential equation-based models can also be used.

Supervisors: Liselotte Jauffred & Namiko Mitarai,