Osteoarthritis (OA) is the most common degenerative joint disorder worldwide and presents with degradation of articular cartilage, leading to loss of joint mobility and function, accompanied by chronic pain.In OA the cartilage extracellular matrix (ECM) composition is actively changing and the articular chondrocytes acquire an altered phenotype in a dramatically changing microenvironment. Chondrocytes are dedicated secretory cells with a primary task in building and maintaining the cartilage ECM. Maintenance of the cartilage ECM demands high numbers of ribosomes to translate large quantities of specific mRNAs into cartilage ECM proteins, such as type II collagen and aggrecan. The mammalian ribosome is a very large protein-RNA complex (>3 MDa; ~80 protein subunits) containing 4 ribosomal RNAs (18S, 5.8S, 28S, 5S rRNAs) that together make-up more than 80% of the total RNA content in a mammalian cell.

Three of these ribosomal RNAs originate from a single template (47S pre-rRNA) that requires extensive processing. Maturation of the 18S, 5.8S and 28S rRNAs takes place by exo- and endo-ribonucleolytic processing. In addition, rRNAs also undergo critical functional maturation via post-transcriptional 2’O-ribose methylation and pseudouridylation of specific rRNA nucleotides. This is achieved via small Nucleolar RNAs (snoRNAs) that specifically guide post-transcriptional modification of the rRNAs.

 The research will be carried out within the Cartilage Molecular Biology group of Dr. T. Welting in the Laboratory for Experimental Orthopedics, department of Orthopedic Surgery, MUMC+. The group has a strong interest and history in chondrocyte molecular biology and RNA biochemistry and is operating in a fully equipped molecular biology lab. At the same time our fundamental research has an important direct connection with the Orthopedic clinic for enabling translational research.

 The PhD-student candidate will be working on a challenging project in which she/he will be studying how micro-environmental conditions relevant to OA impact the chondrocyte’s exo- and endoribonucleolytic processing of 47S pre-rRNA, the post-transcriptional modification landscape of rRNAs, and how snoRNAs interact with the OA chondrocyte phenotype.

• The PhD student has finished a master in Biochemistry, Molecular Biology, Molecular Life Sciences or a related master.

• The PhD student has well-developed general molecular biology skills (for example RNA isolation, gene expression, immunoblotting, northern blotting), experience with molecular cloning, cell culture and transfection skills, and experience with bioluminescence techniques.

• The PhD student is socially competent to work in a multidisciplinary team with excellent communication skills.

• The PhD student has a good set of organizational skills.

Some of our recent relevant publications on this topic:

1. Steinbusch et al.; Serum snoRNAs as biomarkers for joint ageing and post traumatic osteoarthritis. Scientific Reports. 2017 Mar 2;7-43558.

2. Steinbusch et al.; Expression of RMRP RNA is regulated in chondrocyte hypertrophy and determines chondrogenic differentiation. Scientific Reports. 2017: Jul 25;7-6440.

3. Caron et al.; BAPX1/NKX3.2 acts as a chondrocyte hypertrophy molecular switch in osteoarthritis. Arthritis & Rheumatology 2015 Nov;67(11):2944-56.

Fixed-term contract: 48 months.

We offer a full-time position within Maastricht University at the Department of Orthopedic Surgery at the Faculty of Health, Medicine and Life Sciences, School CAPHRI  

Temporary employment for 4 years.

Your salary would be € 2.222,- gross per month in the first year up to € 2.840,- gross per month in the fourth year according to the PhD-student salary scale.

Each year an evaluation will take place.

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 , Support/UM employees/Employment conditions.

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 16,300 students and 4,300 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 Humanities and Sciences, Faculty of Arts and Social Sciences, Faculty of Psychology and Neuroscience.

http://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.

http://www.caphri.nl