Three PhD Fellowships at the Center for Single (micro- and nano-) Particle Science and Engineering (SPSE), Department of Physics, Chemistry and Pharmacy in:
• Advanced Drug Formulation of Hydrophobic Nanoparticles
• Live Cell Imaging, Pathways and Cytotoxicity
• Micro-Pipette Manipulation of Micro-Droplets, Micro-Particles and Interfaces.

The PhD fellowships support our current focus on Anti-Cancer Drug Delivery. The positions are to be filled by 1 September 2014 or soon thereafter.

Job Description
We are looking for highly talented, creative, and motivated candidates to join an interdisciplinary research centre concerned with experimental and theoretical research within the broad fields of Colloid and Surface Science, Micro-Nano-Science, and Cell Biology, with special applications in Anti-Cancer Drug Delivery.

Our main approach in these positions is to reverse engineering nature’s own hydrophobic delivery system - the Low Density lipoprotein (LDL) - and use that knowledge to help develop, characterize, and test new advanced drug formulations for anti-cancer treatment, especially ones targeting metastatic disease.

The rational for using the LDL as an inspiration to deliver anticancer drugs is motivated by two main factors: 1) most of the new cytotoxic and cytostatic drugs that target growth and metabolic pathways have very low aqueous solubility, are usually formulated as oral tablets, and this limits their efficacy which in many cases causes the withdrawal of the drug; and 2) most cancer cells rely on the uptake of LDL to proliferate and survive and numerous malignancies are known to over-express the LDL receptor, including brain, colon, prostate, adrenal, breast, lung, leukemias, and kidney tumours. As a result, cancers are known to take in more LDL than normal cells. In addition, an abundance of LDLR is also a prognostic indicator of metastatic potential.

Position 1. Advanced Drug Formulation of Hydrophobic Nanoparticles
Hydrophobic nanoparticles can be made by using a range of methods, from simple homogenization or solvent injection, to the use of micellar surfactant systems. Especially for hydrophobic anti-cancer drugs, each of these methods has its own advantages and disadvantages, including, available size ranges, and solubility limits and solvency issues. The overall goal of this advanced drug formulation of hydrophobic nanoparticles project is to understand the underlying physical chemistry and materials science in each of these processes, and use this knowledge in the design, fabrication, and characterization of nanoparticles that will eventually find application in anti-cancer therapeutics and diagnostics.

The selected candidate should be familiar with techniques commonly used in colloid and surface chemistry and preferably ones that are used to make and characterize nano-particles, including, Dynamic Light Scattering (DLS), Differential Scanning Calorimetry (DSC), High Pressure Liquid Chromatography (HPLC), Optical Microscopy, Spectroscopy (UV-Vis, Fluorescence), Nuclear Magnetic Resonance.

The PhD research will include:
• Testing a range of physical process-parameters and materials-properties (rates of mixing, solvents, temperature, material solubility, transition temperatures, and crystallinity) on the size and composition of the formed nanoparticles
• Theoretical modelling on nanoparticle nucleation and growth under these various conditions for test materials such as cholesteryl ester and triglycerides, as well as specific hydrophobic drugs and drug derivatives
• Characterizing the nanoparticles for stability (against dissolution and aggregation) in the presence of lipid and other organic sinks
• Incorporation and characterization of hydrophobic-anchored peptides that could ultimately target the LDL receptors on cancer cells.

The selected candidate will be trained in the most advanced techniques in the field of drug-nanoparticle fabrication and synthesis, working in a multidisciplinary project that when coupled to the other two projects will be translated into clinical applications.

Applications for this position should have excellent training in one or more of the following disciplines, preferably at the MSc level:
• Physical chemistr
• Colloid and surface chemistry
• Chemical and Materials processing
• Nano- and bio-technologies, or
• Advanced pharmaceutics.

Position 2. Live Cell Imaging, Pathways and Cytotoxicity
Nanomaterials can enter cell through different intracellular pathways including phagocytosis, clathrin-dependent endocytosis and clathrin-independent pinocytosis. All of above mechanisms follow a similar pattern which involves formation of the membrane-bound endocytic or pinocytic vesicle; maturation of this vesicle into specialized vesicular structures in order to direct the entrapped nanomaterial into specific intracellular compartments; and a final release of the nano-cargo into its final destination (i.e. lysosomes, nucleus, Golgi, or expelled out to the extracellular matrix or another cell). The overall goal of these live cell imaging, pathways and cytotoxicity studies is to obtain a fundamental understanding of the intracellular processes involved in the transport of the synthetic fluorescent nano-particles as well as nano-particlulate drugs.

The selected candidate should be familiar with one or more techniques commonly used in live cell and fixed cell imaging including Spinning Disc Microscopy, Total Internal Reflection Fluorescence (TIRF), Fluorescence Correlation Spectroscopy (FCS), Fluorescence Recovery After Photobleaching (FRAP), Single Particle Tracking. Experience in the techniques of cell and molecular biology is also required. The PhD research will include:

• Measurements of the dynamics of fluorescent nanoparticle uptake in different normal and cancer cell lines using various fluorescence microscopy approaches
• Manipulation and characterization of cells in terms of LDL-receptor knock down and upregulation including RNA and protein analyses.
• Testing novel photostable fluorescent intracellular probes for labelling different cellular compartments (i.e. lysosomes, mitochondria, Golgi).

The selected candidate will be trained in the most advanced techniques in the field of cell imaging, genetic manipulation and cytotoxicity evaluations, specifically in cancer, working in a multidisciplinary project that when coupled to the other two projects will be translated into clinical applications.

Applications for this position should have excellent training in one or more of the following disciplines, preferably at the MSc level:
• Cell Biology
• Molecular Biology
• Biochemistry or Bioengineering
• Optical (fluorescence) Microscopy.

Position 3. Micropipette Manipulation of Micro-droplets, Microparticles and Interfaces
The fundamental technique in SPSE is micropipette manipulation of single and pairs of microparticles, This technique is a highly versatile experimental setup that allows us to carry out multiple studies involving micro-particles of all three states of matter and their five interfaces. For example we have previously evaluated the way gas or liquid microdroplets dissolve in a second solvent, and the microcrystalization or microglassification from liquid microdroplets containing different solutes, polymers or proteins. In addition, it is possible to perform a mechanical characterization of interfacial and membrane-based materials by employing micropipette aspiration, obtaining material properties like elasticity, bending moduli, mechanical strength or shear yield and viscosity. These fundamental studies characterize diffusion coefficients, solubilities, phase behaviour, and interfacial tension that underlie many potential industrial and pharmaceutical applications.

The overall goal of this project is to explore new uses and methodologies of the micropipette technique and use it to inform our nanoparticle formulations, characterizing composition-structure-property relationships at the micro level that translate to nanoparticles.

The selected candidate will be trained in the most advanced techniques in the field of micropipette manipulation and associated micro and nanoscale characterization techniques, working in a multidisciplinary project that will be both fundamental and ,when coupled to the other two projects, translated into clinical applications.

The PhD candidates should therefore have strong interests in both basic and applied research, experiment, and theory. Prior experience with optical microscopy techniques, especially the application of micropipette techniques to colloidal, surface and biologically relevant systems will be a distinct advantage.

Applications for this position should have excellent training in one or more of the following disciplines, preferably at the MSc level:
• Physical chemistry
• Colloid and surface chemistry
• Chemical and Materials processing
• Nano- and bio-technologies

A list of projects aligned with the mission of the centre can be found at our centre website and more details about each PhD position can be found here .

The candidates should be proficient in English, proactive, and possess good interpersonal skills.

For further information please contact Professor David Needham, e-mail: needham@sdu.dk .

Application, salary etc.
Appointment as a PhD Research Fellow is for three years. Employment stops automatically at the end of the period. The holder of the scholarship is not allowed to have other paid employment during the three-year period.

The successful applicant will be employed in accordance with the agreement of 1 July 2013 on salaried PhD scholars between the Ministry of Finance and AC (the Danish Confederation of Professional Associations).

The successful candidate will be enrolled at this university in accordance with faculty regulations and the Danish Ministerial Order on the PhD Programme at the Universities (PhD order).

The university encourages all persons interested in the position to apply, regardless of their age, gender, religious affiliation or ethnic background.

Application must be made in the form of a Declaration of Interest including the following:
• A research proposal/description of your approach to the above project (max one page excluding references)
• A letter stating your specific interest, motivation and qualifications for the project in question (max. two pages) (please attach this under box "Application form")
• Detailed CV, including personal contact information
• Copies of diplomas, Bachelor as well as Master’s degree, including transcript of notes
• At least two signed reference letters.

Further information about the PhD-study can be found at the homepage of the University .

Applications must be submitted electronically using the link below. Attached files must be in Adobe PDF or Word format. Each box can only contain a single file of max. 10 Mb. Please read How to apply before you apply.

Incomplete applications and applications received after the deadline will neither be considered nor evaluated. This also applies to reference letters.

Further information for international applicants about entering and working in Denmark.