Marie Sklodowska-Curie PhD student position in Drug Development - Hiring in process/Finished, not possible to apply

The Department of Pharmacy offers an interdisciplinary environment at the center of the pharmaceutical arena. With frontline research, first-rate education and extensive collaborations we constitute a driving force in the development of our academic field. In this inspiring environment our rich diversity of research groups, several of international prominence, develop and conduct work of great scientific importance. Our core competences include in vitro ADME models, enabling formulations, advanced in vivo methods, computational modelling and simulations, patient and societal aspects from optimising the use of drugs in individuals to societal pharmaceutical policies.

Together, we form a unique cluster of academic competences within pharmaceutical science, playing a key role in shaping the future of pharmacy in both Sweden and globally. Our scientific focus areas in selection: Drug Delivery, Clinical Pharmacy, Molecular Pharmaceutics, Pharmaceutical Nanotechnology, Pharmacodynamics, Pharmacokinetics, Pharmacometrics, Pharmacotherapy, Pharmacoepideminology and Social Pharmacy.

The DRUGtrain Marie Sklodowska-Curie Innovative Training Network focuses on the improvement of drug repurposing and development of compound strategies, with Autosomal Dominant Polycystic Kidney Disease (ADPKD) as example. DRUGtrain offers innovative, multidisciplinary and intersectoral training to nine Early Stage Researchers (ESR) introducing them in the field of drug discovery and repurposing to enhance career perspective in an expanding area that underpins innovative technological development across a range of diverse disciplines. The ESR research projects will address the following key challenges: 1) Identify potential drug targets and drug candidates for repurposing using innovative bio-informatics and cheminformatics approaches; 2) Perform drug testing/drug screenings in advanced in vitro and in vivo models, ultimately leading to testing of new treatment strategies; 3) Clarify drug mechanims, and identify and reduce adverse events using state-of-the-art technologies from in silico and wet lab methodologies. The network consists of six European universities that together with five partners from large and small pharma companies and the health care sector will join forces to train a next generation of multidisciplinary researchers in biomedical and biopharmaceutical sciences. For more information, see Drugtrain.

The project: Briefly, you will first investigate our new repurposing candidate molecules at our profiling platform under the supervision of an experienced drug discovery team. Here, you will apply a series human cellular, subcellular and physicochemical (ADME) assays and analyze the results with state-of-the-art mass spectrometry. You will then participate in the selection of the best performing candidate molecules for further studies. Since the target proteins identified by the partners are localized inside the target cells, you will investigate the intracellular compound concentration available for target interaction. The results will be correlated to the pharmacological response in 3D cultured kidney organoids during a secondment at one of our partners. Then, the global proteomes of the target cells will be quantified and subcellular target and off-target engagement will be investigated using total proteome profiling. Here, you will learn state-of-the-art proteomics, bioinformatics and high-resolution mass spectrometry. Finally, results will be merged with those of other DRUGtrain partners, used in PBPK modelling and the best drug candidate(s) for repurposing will be selected.  Expected Results:

• Pharmaceutical profiling of lead candidates that identify the best repurposing candidates for further optimization.
• Relationship between intracellular drug concentration and pharmacological effect for lead PKD-candidates.
• Understanding subcellular target and off target engagement of lead PKD-candidates.

For recent examples how we use global proteomics, intracellular concentrations and systems pharmacology to investigate fundamental and applied scientific problems in our field, see Ölander, Arch Toxicol, 2019, 93, 819-829 (PMID 30560367) and Mateus, Proc Natl Acad Sci 2017, 114, E6231-E6239 (PMID 28701380) and Wegler, Clin Pharmacol Ther, 2021, 109(3):762-771. doi: 10.1002/cpt.2056. For other examples, see: Artursson group.

The research group: You will be working in professor Per Artursson research group. The group provides an international research environment and has about 20 members equally divided between own research and a collaborative pharmaceutical profiling platform (UDOPP) that participates in national and international drug discovery and development programs. This creates a dynamic research environment that offers expert knowledge across disciplines and a state-of-the art equipment. For more information about Artursson's research group in Drug Delivery, see Drug Delivery.

Duties/Project description: The main duties of doctoral students are to devote themselves time to their research studies, which includes participating in research projects and third cycle courses. Work-related administrative duties are a part of the work. Teaching can be a part of the position (max 20 %). The position will be extended with the time devoted to teaching to allow four years of full time graduate studies. Information about education at the postgraduate level, admission requirements and admission decisions can be found at https://mp.uu.se/web/info/forska/forskarutbildning/medicin-och-farmaci

The PhD candidate is expected to:

• conduct research focused on the discovery and repurposing of novel drug candidates
• developing initiative, creativity and judgement in applying appropriate approaches to research activities
• ensure good day-to-day progress of work in development and analysis, and maintaining good records
• actively participate in all relevant research activities organized by the network as advised by the supervisors
• writing up results for publication and attending suitable conferences for their dissemination, attend meetings as required to discuss the project which could involve occasional international travel
• These duties provide a framework for the role and should not be regarded as a definitive list. Other reasonable duties may be required consistent with the grade of the post.

The research will be carried out at Uppsala University with secondments at University of Konstanz, Germany, OcellO, Leiden, the Netherlands and Certara, Sheffield, United Kingdom.

Qualifications:

• MSc degree in Pharmaceutical Sciences, Drug Discovery and Development, Biomedical or Molecular Biotechnology Engineering, Pharmaceutical modelling, or Cell and Molecular Biology or another relevant field is required.
• Ability to work both independently and also as part of a larger team of researchers, including interaction with the research group and the DRUGtrain ITN and engaging in knowledge-transfer activities where appropriate and feasible.
• Self-motivation and good time management and planning skills.
• Good written and verbal communication skills in English.
• Good presentation and communication skills.
• A commitment to your own continuous professional development.
• Previous experience of any of the core subjects are meritorious.

Additional qualifications: Previous experience with experimental setups, the wet-lab, cell culture, ADME assays, mass spectrometry, bioinformatics, programming and computer modelling are beneficial.

Admission requirements:

A person meets the general admission requirements for third-cycle courses and study programs if he or she:

• has been awarded a second-cycle qualification, or
• has satisfied the requirements for courses comprising at least 240 credits of which at least 60 credits were awarded in the second cycle, or
• has acquired substantially equivalent knowledge in some other way in Sweden or abroad.

Rules governing PhD student candidates are set out in the Higher Education Ordinance Chapter 5, §§ 1-7 and in Uppsala university's rules and guidelines Policies and regulations at Uppsala University

The eligibility criteria for this Marie Skodowska-Curie PhD position are as follows:

• The applicant must, at the date of recruitment, be in the first four years (full-time equivalent research experience) of their research careers and have not been awarded a doctoral degree. This is measured from the date when they obtained the undergraduate degree.
• The applicant must not have resided or carried out their main activity (work, studies, etc.) in the country of the recruiting beneficiary for more than 12 months in the 3 years immediately before the recruitment date.

The advertised project will be carried out by a PhD student (“Early-stage Researcher”) over a period of 48 months.

Instructions for Application: Applications should include:

• cover letter, including a brief description of experience relevant to the position and motivation (max. 2 pages)
• CV with list of publications (if any)
• master thesis (or a draft thereof), copies of diplomas, certificates (including a list of courses and grades) and other relevant documents should be included
• contact information to at least two reference persons. Letter(s) of recommendation are encouraged

Salary: According to local agreement for PhD students.
 
Starting date: 01-09-2021 or as otherwise agreed.

Type of employment: Temporary position according to the Higher Education Ordinance chapter 5 § 7.

Scope of employment: 100 %.

For further information about the position please contact: Professor Per Artursson, telefon +46 70 425 08 88, email per.artursson@farmaci.uu.se.

Please submit your application by 22 May, UFV-PA 2021/1524.

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