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PhD candidate Department Orthopedic Surgery, School Caphri

Osteoarthritis (OA) is the most common degenerative joint disorder worldwide and presents with degradation of articular cartilage, leading to loss of joint …

4 maanden geleden

Arbeidsvoorwaarden

Standplaats:
Minderbroedersberg, Maastricht, Limburg
Dienstverband:
Tijdelijk contract / Tijdelijke opdracht
Uren per week:
36 - 40 uur
Salarisindicatie:
€ 2222 - € 2840 per maand
Opleidingsniveau:
WO

Functieomschrijving

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. The chondrocyte/cartilage differentiation status is central in the progression or even cause of OA. However, established and experimental treatment of OA is mainly symptomatic by alleviating pain and interfering with the cartilage degenerative processes to postpone total joint replacement and does not properly address the underlying molecular pathology.

Recently our group completed the screening of BMP-7 peptides and we were successful in identifying BMP-7 mimicking peptides that favourably change the osteoarthritic chondrocyte phenotype towards a healthy phenotype. However, from a cell signaling point-of-view we do not know how the identified BMP-7 mimicking peptides evoke this potential OA disease-modifying activity. In order to understand the molecular mechanism-of-action behind the bioactivity of our BMP-7 peptides on OA chondrocytes we will be investigating this aspect in this particular project. Targeted as well as non-targeted cellular, biochemical, proteomic and transcriptomic approaches will be considered to identify the main molecular route involved in the OA chondrocyte disease-modifying BMP-7 peptide bioactivity.

This PhD-student project builds further on our recent successful identification of BMP-7 mimicking peptide sequences. Potential intra-articular therapeutical use of these peptides for the treatment of OA requires a solid research effort of which the identification of the mechanism-of-action is one. This project will be carried out in the context of other parallel research projects that are running within our group and that are all dedicated to implementing our BMP-7 peptides as potential OA disease-modifying drugs.

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 is operating in a fully equipped molecular biology lab. Our fundamental molecular research has an important direct connection with the Orthopedic clinic for enabling translational research..

The PhD student will be encouraged to supervise MSc student internships when such opportunities arise.

Functie-eisen

  • 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, pull-down/immunoprecipitation), cell culture and nuclei acid transfection skills, experience with bioluminescence techniques, experience with handling bioinformatics datasets and statistical skills. Article 9 animal license will be advantageous.

  • 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 relevant publications on this topic:

  1. 1. Ripmeester et al.; Recent insights into the contribution of the changing hypertrophic chondrocyte phenotype in the development and progression of osteoarthritis. Frontiers in Bioengineering and Biotechnology. 2018: Mar 19.
  2. 2. Caron et al.; BAPX-1/NKX3-2 acts as a chondrocyte hypertrophy molecular switch in osteoarthritis. Arthritis and Rheumatology. 2015: Nov;67(11):2944-56.
  3. 3. Caron et al.; Hypertrophic differentiation during chondrogenic differentiation of progenitor cells is stimulated by BMP-2 but suppressed by BMP-7. Osteoarthritis and Cartilage. 2013: Apr;21(4):604-13.

Conditions

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.

Additional information

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