Osteoarthritis (OA) is the most common degenerative joint disorder worldwide. Incidencewise it is the fastest growing chronic disease and estimated to grow in the Netherlands from 1.2 million patients in 2015 to 2.2 million patients in the next 20 years. In 2013 it was estimated that worldwide more than 240 million people were suffering from activity-limiting OA of the hip and knee. This is associated with an ever-increasing economic burden due to medical expenditures, lost earnings and loss of job productivity with a total cost of >$50 billion per year in the USA alone. Current treatment of OA is only symptomatic by alleviating pain to postpone end-stage total joint replacement by invasive orthopedic surgery. The lack of pharmacological treatment strategies that effectively tackle the underlying molecular pathobiology of OA leaves an important window for improvement of the molecular treatment of OA and has the promise to revolutionize the treatment of OA or even prevent its occurrence.

Several key growth factors and druggable pathways have been identified in the past decades that are capable of regenerating cartilage and attenuating OA development. However, drugbased treatment of cartilage pathologies comes with critical challenges that are quite unique for the joint: the synovial space is a harsh environment for biologics and treatment of a single joint with biological agents must be applied locally (intra-articular). Due these challenges the targeting of key druggable pathways for cartilage regeneration and OA treatment with biological agents is hampered. Local intra-articular treatment using growth factors is largely incompatible with the synovial space due to their molecular instability. To overcome this important limitation, our group pursues a fundamental research program on the discovery and mechanism-of-action of bioactive peptides for cartilage regeneration and OA treatment. Based on this research we are currently further developing our previously identified lead peptide compounds towards intra-articular application.

In order to take peptide-based OA therapies to the next level, we need to develop advanced technologies to be able to target specific intracellular factors essential in OA pathology. In this OSTASKILLS project we aim to develop a combinatory approach by identifying novel therapeutic peptides that target intracellular OA-pathological processes and optimize peptides for delivery and cell penetration of cell types relevant to the articular joint. The PhDstudent will be designing and testing the effectiveness of different cell penetrating peptides in cell types relevant to the articular joint (such as cartilage and chondrocytes) to target different subcellular compartments, such as the cytoplasm and nucleus. As proof of concept to target intracellular processes relevant to OA, the PhD-student will start with a cell-penetrating peptide that inhibits the inflammatory NF-κB pathway. This peptide will be tested for its inhibitory effect on inflammatory processes related to OA pathogenesis. Furthermore, the PhD-student will be involved in designing and testing additional cell-penetrating peptides that target a variety of intracellular processes relevant to OA, as well as testing combinations with advanced molecular delivery systems. The research will be carried out within the Molecular Cartilage Biology research group of Prof. Dr. T. Welting in the Laboratory for Experimental Orthopedics, department of Orthopedic Surgery, MUMC+, the Netherlands. Part of the research will be done in collaboration with the University of Twente and the University Hospital of Regensburg.

The successful candidate will have a MSc degree in the field of Molecular Life Sciences with a specialization in Biochemistry or Molecular Cell Biology or similar, with experience in general molecular biology, cell/tissue culture, promoter reporter assays, gene expression, immune-based detection techniques and microscopic imaging techniques. The candidate will be open and communicative, proficient in the English language and have good statistical skills. Experience in peptide biochemistry will be highly advantageous. We are looking for a candidate who can work in a multidisciplinary team in a collaborative spirit and with an intrinsic dedication and motivation for Molecular Cell Biology in the field of OA. The PhD student will be participating in Maastricht University educational activities.

Due to the specific requirements of the Marie Sklodowska-Curie co-Fund Innovative Training Network Dutch residents can not apply for a PhD position at Maastricht University but they can apply for a PhD position at other participating Research Institutes in the Ostaskills training network (www.osteoskills.eu).

Fixed-term contract: 4 years.

Temporary employment for 4 years. The first year will be a probation period, after a positive assessment the position will be extended for another 3 years, which happens in the vast majority of cases.

Your salary would be € 2.434,- gross per month in the first year up to € 3.111,- gross per month in the fourth year according to the PhD-candidate salary scale. An 8% holiday and an 8.3% year-end allowance is also provided. Each year an evaluation will take place.

In the final phase of the selection procedure, an assessment takes place.
The idea here is that both, the selection Committee as well as the applicant, can make an informed consideration of it to the PhD programme.

The terms of employment of Maastricht University are set out in the Collective Labour Agreement of Dutch Universities (CAO). Furthermore, local UM provisions also apply. For more information look at the website www.maastrichtuniversity.nl > About UM > Working at UM.

Maastricht University

Maastricht University is renowned for its unique, innovative, problem-based learning system, which is characterized by a small-scale and student-oriented approach. Research at UM is characterized by a multidisciplinary and thematic approach, and is concentrated in research institutes and schools. Maastricht University has around 20,000 students and 4,700 employees. Reflecting the university's strong international profile, a fair amount of both students and staff are from abroad. The university hosts 6 faculties: Faculty of Health, Medicine and Life Sciences, Faculty of Law, School of Business and Economics, Faculty of Science and Engineering, Faculty of Arts and Social Sciences, Faculty of Psychology and Neuroscience. For more information, visit www.maastrichtuniversity.nl.

Department Orthopaedic Surgery, School Caphri

The Department of Orthopaedic Surgery of the Faculty of Health, Medicine and Life Sciences (FHML) of the Maastricht University Medical Center, in Maastricht, the Netherlands has a long-standing clinical expertise in prosthethic treatment of osteoarthritis and regeneration of cartilage defects. The Laboratory for Experimental Orthopedics is a young, enthusiastic and multidisciplinary team with an established specialization in chondrocyte cell biological and –molecular research for the fields of osteoarthritis and skeletal development.