Postdoc on Tumor and Lymph node on chip platform for cancer studies

Cancer is the second cause of death worldwide and it is estimated that metastases are responsible for as many as 90% of cancer deaths. It is believed that up to 70% of metastases occurs through the lymphatic system with lymphatic vessels and lymph nodes (LN) mediating the process, while the rest of them are of hematogenous origin and occur through the blood stream. LN metastasis is an independent indicator of poor prognosis. LNs are responsible for the immune response against external threats as well as the elimination of tumor cells which are considered foreign entities. Tumor cells however, have found ways to escape the immune system and even colonize LNs, which would be considered an otherwise 'hostile' environment. Initially, this is achieved through secreted signals that travel to the lymph node and prepare the field, while later cancer cells migrating and homing the LN actively suppress the local immune response. Nowadays, immune response reactivation is the basis of immunotherapy success in cancer treatment. Understanding how tumors shape the LN environment and how tumor cells metastasizing to the LNs are able to suppress the immune response locally is a breakthrough, and it will help us identify novel biomarkers, and possibly targeted therapies which could be combined with existing anticancer therapies. Studying the metastatic process in real time, and doing so for individual cancer patients in a personalized manner that would also enable parallel preclinical drug testing of multiple drugs and combinations, is not possible with current methodologies.

With a number of research institutes and companies throughout Europe, we will develop and validate a tumor-lymph node-on-chip (Tumor-LN-oC) platform composed of 3D tissue models and microfluidic chips which will connect surgically removed human primary tumors and LN tissue from the same lung cancer patient. This will serve as a 'biological twin' of the patient and will allow us to study the interaction of primary tumors with LNs for individual patients. This will enable the use of existing drugs, or the development of new ones that could reverse this process and inhibit tumor growth and dissemination. It will also allow the identification of novel biomarkers characterizing metastatic cells which could also be exploited therapeutically. Moreover, by employing novel imaging approaches, we will generate a spectral 'finger-print' of migrating/metastasizing cells which could be used for diagnostic purposes in tumor and lymph node biopsies. The proposed technologies will provide added value to the EU cancer diagnostics and pharmaceutical industries and lower the barriers associated with the application of Organ-on-Chip technology in disease diagnosis and therapy.

The goal of this postdoc position is to improve the current chip design, especially regarding biocompatibility. We have an existing prototype (developed during the past three years) being produced in the Microfablab at TU/e and tested by our EU partners for integration and applications. However, there are still some issues remaining regarding the chip, including suitability of long term cell culture, material robustness and fluid flow. Your job is to validate and help improve the chip design by setting up and perform various cell culture experiments, troubleshoot together with the engineering team, and possibly design and perform follow-up research based on the improved chip.

The duration of this postdoc can be between 6 months and 1 year.



Figure: Tumor-LN-oC integrated with artificial cilia. (a) micromoulded magnetic artificial cilia;
(b) a proposed chip design: top part: two compartments for tumor and LN samples collected from patient (COC); middle part: microfluidic circuitry for feeding and facilitating cell migration (glass), connected to top part via porous membranes; bottom: mid-IR transparent substrate (CaF2) with fixed artificial cilia patch; (c) connecting micro-channels.

Embedding

The postdoc will be supervised by Dr. Ye Wang and Prof. Jaap den Toonder from the Microsystems group. The Microsystems group is part of the Institute of Complex Molecular Systems (ICMS). The Microsystems group manages the Microfab/lab, a state-of-the-art micro fabrication facility that houses a range of micro manufacturing technologies - microfluidics technology is one of the main research pillars of the group. The candidate will also work closely with experts from Biomedical department from TU/e, and work in their state-of-the-art cell lab. The activities are part of the European research project Tumor-LN-oC, and there will be many interactions and collaborations with the other project partners.

Requirements:

• ambitious, self-motivated and proactive;
• strong biology/biomedical background, with extensive experience in developing cell culture protocols, preferably in novel in vitro platforms;
• have experience in working in multidisciplinary projects, preferably combining mechanical, physical and/or biological disciplines;
• experience in microfluidics and/or microfabrication is preferable;
• good communication skills in written and spoken English;
• willing to contribute to education activities, such as supervising BSc and MSc projects.

Salary Benefits:

A meaningful job in a dynamic and ambitious university, in an interdisciplinary setting and within an international network. You will work on a beautiful, green campus within walking distance of the central train station. In addition, we offer you:

• Full-time employment for 6 to 12 months.
• Salary in accordance with the Collective Labour Agreement for Dutch Universities, scale 10 (min. €3,877 max. €5,090).
• A year-end bonus of 8.3% and annual vacation pay of 8%.
• High-quality training programs on general skills, didactics and topics related to research and valorization.
• An excellent technical infrastructure, on-campus children's day care and sports facilities.
• Partially paid parental leave and an allowance for commuting, working from home and internet costs.
• A TU/e Postdoc Association that helps you to build a stronger and broader academic and personal network, and offers tailored support, training and workshops.
• A Staff Immigration Team is available for international candidates, as are a tax compensation scheme (the 30% facility) and a compensation for moving expenses.

38 hours per week

De Rondom 70