Interview with Antigoni Gogolou, PhD student in CONNECT Nervous-system-on-Chip

Miss Antigoni Gogolou is a PhD student in the Tsakiridis Lab at University of Sheffield working on cell fate specification using human pluripotent stem cell- derived neural crest cells with a focus on the development of the enteric nervous system.Her scientific academic career started with her 5-year Degree (integrated Masters) in Applied Biology from the University of Ioannina in Greece, where she graduated in the top 3% of the entire course. During the final year of her studies, she carried out her diploma thesis project in the laboratory of Androniki Kretsovali at the Institute of Molecular Biology and Biotechnology in Greece, where she worked on the study of early embryonic development using mouse embryonic stem cells. In 2018, Antigoni decided to expand her knowledge on human embryonic stem cell biology through a 5 months internship in the Tsakiridis laboratory at the University of Sheffield, after receiving an Erasmus+ grant. Her interest in developmental biology, led her to pursue a PhD in the same group and her current work focuses on enteric nervous system development through the use of human pluripotent stem cells (hPSCs).

What is the objective of your project? What outcomes do you expect after completing your second year of your PhD studies?

The aim of the project is to construct a physiologically relevant enteric nervous system on a dish, that contains the appropriate enteric neural and glial components in content and at the correct numbers. By integrating our knowledge in hPSC differentiation with developmental biology, we aim to deliver an easy to follow and reproducible protocol to generate enteric neurons and glia, that can be used to study enteric nervous system (ENS) development and disease. Our ultimate goal, in the framework of CONNECT, is to combine hPSC-derived peripheral nervous system elements such as peripheral nerves and enteric neurons with brain organoids, developed by our partners, on a single smart chip to study the connectivity between different parts of the nervous system, a factor which has been found to play a profound role in neurodegenerative disorders such as Parkinson’s disease. We are currently in the process of characterising the hPSC-derived ENS components and towards the end of the second year of my PhD, I set my sights on having an optimised protocol developed.

What comes to your mind when you hear chip technology and why do you think it makes a difference to apply chip technology to enteric neuron biology?

As everyone else who is not an expert in microelectronics, the first thing that crosses my mind when I hear chip technology is the conventional computer chip with all the integrated microcircuits. However, in our case we are talking about sophisticated and elegantly designed micro-fluidic cell culture devices, that support cell growth and allow experiments to be done on living cells by providing stable conditions that mimic the natural environment. Luckily, chip technology and more specifically organ-on-chip technology, has attracted a great amount of interest nowadays, so that more and more people have become familiar with it. Combining chip technology with our living cells will not only add complexity and the required three-dimensional aspect to our system but will facilitate controlling and monitoring the cellular microenvironment, the major source of variability in cell culture. The application of chip technology to enteric neuron biology is likely to provide a more accurate model of human ENS development, surpassing the need of traditional animal models and the ethical issues associated with their use.

Are you planning to attend a conference presenting your research results soon? If yes, please tell us a bit more about the type of conference and who the main attendees are? Are there also participants from industry, representatives of patient groups or medical specialists?

I was planning to attend and give a poster presentation in Gastronauts, a symposium taking place in Nantes in May 2020, however, due to COVID-19 pandemic, unfortunately the organisers decided to postpone it for May 2021. Gastronauts Nantes is a symposium on gut-brain axis matters with a full agenda of exciting and multidisciplinary research from gut neurobiology to synthetic biology and bioengineering, primarily led by scientists from an academic environment. The attendee list includes students, post-docs, PIs, people from industry and in general, anyone who is interested in gut biology of a broader scope and is keen to share their enthusiasm with peers in the field.

In your own words, how do you think does CONNECT make a difference to society?

CONNECT’s holistic approach by integrating fully connected cultured organ systems such as central, peripheral and enteric nervous system provides a better insight into human physiology and offers a highly interconnected complex system that precisely emulates in vivo function from cell to organ level. Developing an in vitro full organ system like the CONNECT platform, will be highly beneficial to society for ethical and practical reasons. The CONNECT project will not only provide a tractable and reproducible system to model disease development and progression, but will also advance drug discovery by enabling high-throughput screening. Moreover, I believe that CONNECT’s novel approach will open up new venues for personalised medicine and the development of treatments tailored to patient’s health needs by using drug candidates on patient derived cells. 

Interview with Yagmur Demircan Yalçin, Postdoc in CONNECT Nervous-system-on-Chip

Dr. Demircan Yalcin is a postdoctoral fellow of Neuro-Nanoscale Engineering at the Microsystems section in the Department of Mechanical Engineering, Eindhoven University of Technology, The Netherlands. She is working on the design and implementation of novel micro physiological sensors, which combine electrical and mechanical modalities. By using her hands-on experience with 3D electrodes in analyzing the biological cells in microfluidics applications, she focuses with her current research on “robustly re-using 3D MEAs in nervous-systems-on-a-chip: novel platforms and best practices”

Dr. Demircan Yalcin received her, B.Sc., MSc, PhD in Electrical and Electronics Engineering from the Middle East Technical University, Ankara, Turkey in 2010, 2013 and 2018, respectively and she also has a Minor Degree in Biology from the same university. She received her PhD. on the topic: A Lab-on-a-chip System Integrating Dielectrophoretic Detection and Impedance Counting Units for Chemotherapy Guidance in Leukemia. Before joining Neuro-Nanoscale Engineering at TU/e in January 2020, she worked at Mikro Biyosistemler, Ankara, Turkey as an R&D Engineer from 2015 to 2019.

What is the objective of your postdoctoral studies in CONNECT?

I am enthusiastic in combining engineering with biology. I already had the opportunity to be included in the development of a pioneering Lab-on-a-Chip diagnostic platform to provide better healthcare for people since I started my research life as a Master student 10 years ago. I observed that the creation of engineering tools to discover and understand biological mechanisms takes place at the interface of disciplines. In the CONNECT project, I believe this knowledge can make a difference because my scientific objective for CONNECT is the design and fabrication of an electrophysiological readout method being integrated with the microfluidic 3D cell culture environment of the novel Nervous-system-on-Chip. The CONNECT platform incorporates knowledge from lots of scientists from different areas. My personal objective for CONNECT is to act as a bridge between engineers and biologists by using my interdisciplinary background, including theoretical and practical experiences.

What do you think (from the viewpoint of your respective scientific discipline) is the biggest challenge in combining chip technology with neurobiology?

Real-time and label-free monitoring is the main challenge in my opinion because finding of a cost-effective material which has suitable properties to provide a proper environment for living cells and to make high resolution monitoring possible is difficult.

If you were meeting an investor in an elevator, what would be your 15 seconds Message Map to pitch to this CONNECT stakeholder the importance of putting the next level in vitro model systems for the nervous system firmly on the map?

Research in CONNECT links the nervous system of the brain and the gut in one single chip to understand mechanisms behind neurodegenerative diseases like Parkinson. CONNECT is an organ on a chip platform based on novel findings in stem cell technology and advances in microfluidics. It aims to increase the success of drug discovery studies and reduce the need of animal tests.

Is there something else you want to add?

Especially for the development of novel healthcare technology, working together across different scientific disciplines and types of technology is key. The different approaches and terminologies used in these diverse fields of research make effective collaboration a real challenge.  However, it becomes really interesting and enjoyable after starting to understand the language of others. CONNECT literally connects us to be open minded in evaluating our findings not only from our own but also from the perspective of other disciplines including the neurosciences, which urgently seeks to apply nervous-systems-on-chip technology to advance their frontiers.

Interview with Gemma Gomez Giro, Postdoc in CONNECT Nervous-system-on-Chip

Dr. Gemma Gomez-Giro is a postdoctoral researcher at the Luxembourg Centre for Systems Biomedicine of the University of Luxembourg in the Developmental & Cellular Biology group (Schwamborn Lab).

Dr. Gemma Gomez-Giro received her B.Sc. in Biomedicine from the Autònoma University in Barcelona, Spain, in 2013 and continued with her master studies at the Pompeu Fabra University in the same region. After completing her MSc degree she moved to Munich, Germany, with an Erasmus+ grant pursuing her wish to investigate neurodegenerative diseases. Following her interest in neurodegenerative disorders, in 2015 she started her PhD in Biology at the Westfälische Wilhelms-Universität in Münster, Germany. She received her degree in 2019 on the topic: Modelling Juvenile Neuronal Ceroid Lipofuscinosis by genome editing in human induced pluripotent stem cells and cerebral organoids.

What is the objective of your postdoctoral studies in CONNECT?

The objective of my postdoctoral studies in CONNECT is to help integrate the knowledge we have gathered in the Schwamborn lab concerning neurodevelopment and 3D organoid culture technology in order to achieve a functional connection between different elements of the nervous system. It is my goal to participate in the production and up-scaling of the central nervous system compartment, which should contain all the necessary elements to establish a network with the other elements on the chip. It is also my objective to work on the application of the system to study Parkinson’s disease.

What do you think (from the viewpoint of your respective scientific discipline) is the biggest challenge in combining chip technology with neurobiology?

In my opinion, the random configuration of organoid 3D cultures makes it difficult to precisely control their growth and directionality. However, on-chip platforms are already developing better tools to achieve more guidance and monitoring of the microenvironment, overcoming at the same time concerns regarding reproducibility. I believe the biggest challenge when bringing both aspects together is the need to incorporate multi-omics readouts and advanced imaging techniques to be able to capture interactions and physiological responses at the systemic level and gather high-throughput data from the microfluidic system. Necessarily, this has to be paired with advances in computational models that can support such data analysis in order to achieve faster and reliable outcomes.

If you were meeting an investor in an elevator, what would be your 15 seconds Message Map to pitch to this CONNECT stakeholder the importance of putting the next level in vitro model systems for the nervous system firmly on the map?

In the CONNECT project we believe that it is not possible to explain complex neurodegenerative diseases by looking at the different systems affected separately. Therefore, we aim to increase the complexity level of in vitro systems to establish a functional connection between different elements of the nervous system. In order to do that, the advances in on-chip technologies are crucial in helping us establish, examine and measure this interaction. CONNECT represents an important bridge from the bench to translational medicine, allowing us to gain insight in Parkinson’s disease pathology mechanisms. Moreover, CONNECT is an innovative, improved and attractive in vitro screening platform that could reduce time and cost of drug development and testing, replacing animal experimentation.