PhD-student Department Orthopedic Surgery, School Caphri

PhD-student The Department Orthopedic Surgery, School Caphri at Maastricht University/MUMC+ has a vacancy for a PhD-student.

Job Specifications - (uitleg)

Solliciteer binnen 23 dagen op deze vacature

Job Description

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. Biochemically, OA is characterized by synthesis of extracellular matrix-degrading enzymes (ECM), such as aggrecanases (a disintegrin and metalloproteinase with trombospondine motifs (ADAMTSs)) and matrix metalloproteinases (MMPs), resulting in the active breakdown of the cartilage tissue matrix. The analogy between endochondral ossification and OA progression has been widely recognized and many of the cartilage degrading and mineralization enzymes that are secreted by hypertrophic chondrocytes in the growth plate are also crucially involved in OA. This may place, next to the local inflammatory condition (amongst others caused by synovitis), the chondrocyte/cartilage differentiation status central in the progression or even cause of OA. Established and experimental treatment of OA is mainly symptomatic by alleviating pain and interfering with the cartilage degenerative processes to postpone total joint replacement.

An exciting treatment option that may uniquely address the chondrocyte and cartilage differentiation status/phenotype is bone morphogenetic protein 7 (BMP-7, also called OP-1). A phase-1 clinical trial has been completed in OA patients and reported no serious adverse events after intra-articular injection of BMP-7. In congruency with this, our previous work unveiled exciting and previously unrecognized features of BMP-7. It actively suppresses the (OA) chondrocyte hypertrophic phenotype and may provide a cell biological basis to target the chondrocyte phenotype in OA.

Recently we completed the screening of BMP-7 peptides and were successful in identifying BMP-7 mimicking peptides. In order to prepare these peptide sequences for efficacy studies, we need to further optimize these BMP-7 mimicking peptides. Optimization will include the isolation of their core amino acid moiety prerequisites to achieve a minimal and highly specific peptide that includes all crucial and supporting amino acid residues for carrying out their bioactivity. The proteolytic stability of the most promising minimal consensus peptides will be addressed by amino acid isomerization and targeting the peptide backbone, as well as conformationally constraining the peptides. In vitro, ex vivo and in vivo experiments are planned to investigate the molecular working mechanism of these peptides and to test their OA disease modifying efficacy.

Requirements

This PhD-student project builds further on our recent successful identification of BMP-7 mimicking peptide sequences. Potential intra-articular therapeutical use requires further fine-tuning of these sequences and their biochemistry. We expect that we will be able to address the process of fine-tuning and end up with optimized peptides that we will be testing in accepted models for OA as well as determining their molecular mechanism of action. The end product of this research is expected to result in unique peptide biochemistry and peptide sequences and pave the way for near-future pre-clinical testing of OA disease modifying efficacy.

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, (immuno)histochemistry and microscopic techniques. The candidate will be open and communicative, proficient in the English language and have good statistical skills. Art. 9 animal certification and experience in molecular cloning will be 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. The PhD student will be encouraged to supervise MSc thesis students when such opportunities arise.

Conditions

We offer a full-time position (38 hours/week) 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. 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, employees, A-Z.

Employment: Temporary, 48 months

Organisation

http://www.maastrichtuniversity.nl/

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 16,000 students and 4,000 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.

Department

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.

Additional Information

Dr. Tim JM Welting, Department of Orthopedic Surgery
Tel. +31433884157, Email: t.welting@maastrichtuniversity.nl