Praktikumsbericht – Jakob Klinger

Work as Member of Levings Research Team at UBC

School of Biomedical Engineering

Introduction

Gene editing of living cells is a cornerstone of present-day medical research that has enabled scientists to address fundamental biologic questions and identify novel strategies to treat diseases. The ability to manipulate adoptive cell therapy products has revolutionized cancer immunotherapy and promises similar results for the treatment of autoimmune diseases, inflammatory disorders, and transplant rejection. Clinical trials have recently deemed polyclonal regulatory T (Treg) cell therapy to be a safe therapeutic option, but questions remain regarding the efficacy of this approach.[1]

During my internship mid-July 2023, I worked as part of Megan Levings research team in order gain scientific work experience of a mostly unknown but very interesting subject. Over the time of two weeks in Vancouver I was allowed to work in the Lab with various specialists, attended multiple group meetings and got to hear two master defensives, as well as a symposium at the main UBC campus.

UBC

Cooperation with BC Children’s Hospital

The BC Children’s Hospital, located in Vancouver, British Columbia, is a beacon of hope and healing for children and families in the region and beyond. Since its inception, this world-class pediatric facility has been dedicated to providing exceptional medical care, research, and education to address the unique healthcare needs of children.

A significant aspect of the BC Children’s Hospital’s success lies in its collaborative partnership with the University of British Columbia (UBC). This partnership exemplifies the synergy between cutting-edge medical research and practical, compassionate healthcare. UBC’s Faculty of Medicine and the hospital work hand in hand to advance medical knowledge, develop innovative treatments, and train the next generation of healthcare professionals.

Megan Levings research team

Dr. Megan Levings is an internationally recognised Professor in the Department of Surgery and School of Biomedical Engineering at the University of British Columbia and BC Children’s Hospital Research Institute. Her lab studies how a special kind of white blood cell, known as a T regulatory cell, could be used as a cellular therapy to stop harmful immune responses.

Personal Experience

During my internship, I learned in small bits how gene editing technologies are being applied to transform the future of Treg cell therapy, focusing on the preclinical strategies that are currently being investigated to enhance the efficacy, function, and survival of human Treg cells. We explored approaches that may be used to generate immunoregulatory cells ex vivo, detail emerging strategies that are being used to modify these cells (such as using chimeric antigen receptors to confer antigen specificity), and outline concepts that have been explored to repurpose conventional T cells to target and destroy autoreactive and alloreactive lymphocytes.

Besides all the theoretical approaches, I was introduced by Lorna, a new technician of Megans Team, to the everyday work of the lab and was told how to work safely in different environments. After completing a mandatory online safety course, I was encouraged to prepare MaxiPreps in order to grow bacteria in the incubator at 37°C. It takes about 12 to 16 hours, mostly done over-night. Further on, separating individual cells from clusters, counting, and testing their viability was a key step. Being cautious about contamination I was introduced to work under the fume hood – a ventilation device to keep bacteria and virus from intoxicating the room. Preparing the right cells was essential but finding the right enzyme to extract the needed DNA was even more crucial. A variety of computer-programs help you find the right models, but as you test them, you’ll quickly find out, that theory is very limited. By placing the DNA in a so-called Run-Gel, we were able to specify which enzyme actually cuts the DNA at the needed place. I also learned about the key hurdles that currently hinder the clinical adoption of Treg cell therapy and thought of potential future avenues of research for this field. Regulatory T cells are now being tested on humans but only produced in advised labs around the world. Mass production, but especially transportation of more than 500ml of cells with media (nutrition) poses a problem. Not only do you have to freeze big batches of cells slowly, but also have to find a mode of transportation where no cells will die due to temperature shocks or other damage.

Working times were dependant on the workload and tasks to do. They could vary from five to nine hours a day. Afterwards I had dinner either at home or went out for amazing food one of many cultures that Vancouver has to offer. Especially fish is not comparable to what can be found in local german supermarkets and restaurants. Cinnamon-rolls are also the best here. A sunset canoe-trip in front of the YVR skyline, a trip to Granville Island, to downtown and east and south Vancouver were the activities on weekend days. Granville Island is a small island located southwest of downtown and provides playing areas but is mostly known for its food markets and amusement centre. Also, navigating through downtown and meeting lots of new people helped me relearn simple english phrases and improve my english. It‘s especially easy here because people are really relaxed, friendly and spontaneous!

In the end I‘d like to thank Megan Levings, the whole family, the TUMKolleg, but most importantly the whole Lab for making my internship at UBC and the stay in Vancouver an unforgettable, vivid and somewhat relaxing experience. Canadian lifestyle is just different! You should try!

Travel Advice

While booking your trip to Canada, make sure to first complete your electronic Travel Authorisation (eTA). You are always visiting as a tourist – unless you get paid but don’t make things complicated! Please be aware of your age at the time of traveling and bring all requested documents. All flights from Europe arrive at the same time as flights from Turkey and India – border control are therefore no jokes.

Lufthansa doesn’t provide power-outlets on the flight from Munich – only USB-A. Charge your device accordingly to work plans to avoid running low on battery at customs.

I didn’t find myself in the need of mobile network or data as almost every bus has wifi. For getting around I highly recommend acquiring a compass card or just use your credit card to pay for public transport.

Pictures

More high-quality impressions of the Lab and Vancouver, such as Downtown, Steveston and Granville Island can be found here. Feel free to have a look!

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[1]  (J Allergy Clin Immunol 2022;149:1-11.)