What you are going to do

Background
Psoriasis is an inflammatory skin disease affecting a substantial portion of the population. Current therapies require continuous treatment and pose a substantial burden on healthcare systems. Previous limited work on the treatment of psoriatic lesions of thin skin by pulsed laser therapy, the so-called selective photo thermolysis (SPT), indicates that this can be effective, resulting in a long duration of remission of years rather than the more common weeks or months. However, the working mechanism of this therapy is unknown, and therefore optimization and application in clinical practice is problematic.

This project is part of a TKI research Project in which Principal Investigators from the Biomedical Engineering & Physics department of the Amsterdam UMC (AMC) work closely together with two commercial partners. We hypothesize that SPT reduces the dermal inflammation by destruction of the increased perivascular nerve endings that are observed in psoriatic skin lesions, via heating of the blood vessels. Two PhD students will work together to elucidate the mechanism of action by which photothermal therapy is able to downregulate the immunological overexpression typical of psoriasis and to develop a model to predict laser settings for individualized optimal treatment.

Goals and description
The physical effect of photothermal therapies is a complex interplay between the number of photons present in the tissue and their local absorption. Their product generates the heat that diffuses towards the nerve endings, resulting in the final effect. All these processes are time dependent and are further complicated by the effect of cooling by the presence of blood flow (convection) and the time dependent Arrhenius relation for damage. In addition, the local heating causes a series of biological events related to the vasculature, innervation and inflammation. PhD 1 will work on the physical aspects, while PhD 2 will address the biology.

The task of PhD 1 in the project is to work on the precise physical mechanism and effects of photothermal therapy. Therefore, a new computer model that includes optical and structural properties of the skin and dynamic properties like blood flow and heat diffusion/convection has to be developed. Using this model, a new method to determine the optical properties of tissue will be developed and validated. You will also optimize efficient and cost-effective imaging such as laser speckle contrast, hyperspectral and high-speed thermal imaging methods in order to determine the physical and physiological effects of the treatment. The acquired data is finally analysed using the developed computer models as to relate skin composition with thermal effects.

As PhD 2, you will study the role of perivascular nerves in leukocyte transmigration over the vascular wall. Our working hypothesis is that these nerves interact with both the leukocytes and vascular endothelial cells to facilitate this process, and that suppression of nerve function therefore blocks the local inflammation seen in psoriasis and many other inflammatory diseases. You will study these interactions using e.g. blockers of neurotransmitters and will unravel the effects of heating on function of perivascular neurons. You will work with model systems, including co-cultured cells, isolated blood vessels, in vivo approaches, as well as with tissue samples obtained from psoriasis patients. Your methods further include advanced microscopy, immunohistochemistry and other molecular diagnostic techniques.

By validation of these models with the experimental results, this work will provide a solid base for further development of optimal SPT in psoriasis.

What we expect from you

For PhD 1 (physics):

• A MSc degree in physics, biomedical engineering or a related field;
• An affinity for optics;
• Interested in performing simulations to develop and validate the measurement setup;
• Knowledge of MATLAB and/or computing languages is a clear advantage.

For PhD 2 (biology):

• A MSc degree in biology, biomedical sciences or related;
• Eagerness to address the biology of complex clinical problems;
• An interest in vascular biology and inflammation;
• Experience in wet lab work.

For both PhD students:

• Ability to combine practical skills with analytical insight;
• Ability to function in a highly interdisciplinary team, with mutual interest in the physical and biological aspects of the work.

What we offer you
We offer you ample opportunity for development, deepening and broadening, additional training and a place to grow! Working at AMR means working in an inspiring and professional environment where development is encouraged in every respect.

• The maximum gross monthly salary based on a 36-hour work week is € 3.103,- (scale UMS CAO UMC).
• The base salary does not include holiday pay (8%) and a year-end bonus (8.3%).
• We offer a contract for 48 months.
• In addition to excellent accessibility by public transport, AMC also has a sufficient number of parking spaces for employees.
• Pension is accrued at Be Frank.
• The opportunity to attend international progress meetings, scientific conferences and summer schools.
• An opportunity to build your own network in biomedical research.
• A PhD degree at the University of Amsterdam, after successful completion of your research.

For an overview of all our other terms of employment, see https://werkenbijamc.nl/arbeidsvoorwaarden-amr/

Where you are going to work
This project is a collaboration of Prof Ton van Leeuwen, Prof Maurice Aalders and Prof Ed van Bavel at the AMC Department of Biomedical Engineering & Physics, Forensic technical Solutions BV and ZBC MultiCare BV.

The department of Biomedical Engineering & Physics in the AMC has ample experience with the simulation and measurement of effects of laser treatments of skin malformations, developing and validating new diagnostic methods, and light distribution modelling. Moreover we have a long track record on vascular research, including microvascular endothelial biology, employing a range of unique and innovative technologies.