The use of immune modulating agents to “wake up” the immune system in patients is a remarkable breakthrough in cancer treatment. But despite their sophistication, only a minority of patients (e.g. 20% of melanoma and lung cancer) benefit from these new drugs. The causes of treatment failures are immensely complicated and multifactorial. Effective treatment depends on delivery of the correct combination of therapeutic agents at the malignant site, with minimal effect at healthy sites in the body. The proposed project aims to build on the proof-of-principle we established in earlier research: that tumor-colonizing Clostridium bacteria can continuously secrete high doses of biologically active therapeutics exclusively at the tumor site (Kubiak et al, Front Microbiol 2021). We hypothesise that the full potential of current immunotherapies can be realised through a more intelligent method of delivery to the tumour. Recombinant Clostridium, engineered to express genetically encoded therapeutics, will colonize solid tumors from where they will secrete cytokines and antibodies directly into the tumor micro-environment. Due to the precise nature of this “delivery vehicle”, the systemic toxic effects observed in all current immunotherapies will be prevented.

Using a translational approach, anti-tumor effects and activity and responsiveness of the immune system will be determined and modulated in relevant preclinical cancer models, upon systemic administration of recombinant non-pathogenic clostridial spores expressing a variety of therapeutic agents, alone and in combination with other treatment modalities. Through our results, we expect to demonstrate the superior therapeutic effect of delivering established immunotherapeutic agents to solid tumors with no negative effects on healthy tissues using recombinant Clostridium.

The research will be carried out within The M-lab, Department of Precision Medicine (GROW Research School, University Maastricht). The proposed work will be performed under the responsibility of Prof. Lambin, PI’s Dr. Theys and Dr. Dubois and senior researcher Dr. Bailey.

The team has extensive expertise in the field of oncology, radiotherapy, immunotherapy and

Clostridium with a proven track record. The experimental design, further execution of the proposed work and scientific reporting will be the responsibility of the candidate. He/she will directly supervise the animal technician and plan these experiments in close collaboration with him/her. Tight collaboration and scientific networking will enable to keep the community updated about our latest developments, to trigger interest in the novel combination approach, and to reach a global scientific audience.

We seek a talented PhD candidate to join our interdisciplinary team. You will be performing translational oncology studies involving in vivo experiments as well as immunological and tumor-specific analyses will be performed to evaluate the effect of the recombinant clostridia directed specifically towards the tumor and its micro-environment. These analyses include tumor growth follow-up and quantification of tumor micro-environmental and flowcytometric-based immunological parameters. In a next step, you will quantify the therapeutic ratio of the Clostridium-mediated immunotherapy approach in various combinatorial treatment settings.

Under dedicated supervision, you will be responsible to successfully complete your PhD training program, present at (inter)national scientific conferences and report in scientific renowned journals.

Requirements:

• The candidate finished a Master in Biomedical Sciences, Medical Biology, Life Sciences or a related Master;
• The candidate has a strong and enthusiastic motivation for a PhD track in translational public health research;
• The candidate has affinity with the fields of microbiology, oncology and immunology;
• The candidate has well-developed general molecular biology skills (RNA/DNA isolation, gene expression, qPCR, immunoblotting,..), experience with cell culture, flow cytometry, staining procedures and microscopy;
• A license to and has experience with work with experimental animals is a strong plus;
• The candidate has excellent writing skills;
• The candidate has an analytical mind-set and an independent work attitude;
• The candidate has the profile of a team player with good communication skills (in English) and a respectful attitude towards colleagues and collaborators.

Fixed-term contract: 4 years.

Temporary (full-time) 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 € 2.395,- gross per month in the first year up to € 3.061,- 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.

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 http://www.maastrichtuniversity.nl > Support > UM employees.

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 of Precision Medicine

The Precision Medicine department at FHML consists of two laboratories, each with its own type of research:

• The "dry lab" (The D-Lab) is focused on building multi-factorial decision support systems with a focus on quantitative image analysis (view the animation: https://vimeo.com/241154708) and data management.
• The "wet lab", (The M-Lab) is focused on translational research aiming at targeting the tumor microenvironment, metabolism and the immune system of tumors.

The department has a longstanding expertise in preclinical oncology research and has extensive experience with big data analysis. We are a young, enthusiastic and multidisciplinary team with wide expertise covering research with (pre)clinical data, clinical studies and "virtual clinical trials". 

This together with internal and external collaborations (both on national and international level) with fundamental scientists and clinicians ensures top-notch research with high scientific and social impact.