Aspidelaps lubricus snake crawling in front of a fluorescent microscopy image of snake venom gland organoids. Credit: Ravian van Ineveld, copyright Princess Maxima Center for Pediatric Oncology. 9 March 2021 Thesis defense Jens Puschhof: “Investigations on epithelial biology using organoid differentiation and co-cultures” Back to news Jens Puschhof, from the group of Hans Clevers, successfully defended his thesis titled “Investigations on epithelial biology using organoid differentiation and co-cultures: Building representative models of the snake venom gland and complex tissue interactions in cancer and metabolic diseases” on the 9th of March. His thesis was awarded the rare qualification cum laude. Using organoid technology, he discovered that a certain strain of bacteria can cause mutations that contribute to the development of colorectal cancer in humans. “Understanding what causes cancer is an important step towards prevention.” Puschhof labels his PhD trajectory “diverse”, but organoid technology is definitely the unifying factor. Organoids are miniature 3D structures that mimic the function of actual organs. During his PhD, he used various kinds of organoids for different purposes and thereby demonstrates the enormous range of possibilities that the relatively new technology has to offer. Bacteria leave their mark in cancer First, Puschhof and colleagues grew organoids from the tissue of healthy human intestines and injected them with bacteria. They discovered that the bacteria caused a pattern of mutations in the DNA of the gut-organoids that is also present in the DNA of patients with colorectal cancer. Puschhof explains: “It is really difficult to pinpoint the causation of mutations, and ultimately cancer, to individual factors. That is why organoids are so helpful; we can really rebuild the entire system step-by-step in the lab and compare it to data from patients.” The next step is to find out when the bacteria start causing the mutations and how this process can be interfered with. “Understanding how bacteria contribute to the development of cancer is important for eventually reaching our ultimate goal: prevention.” Aspidelaps lubricus snake crawling in front of a fluorescent microscopy image of snake venom gland organoids. Credit: Ravian van Ineveld, copyright Princess Maxima Center for Pediatric Oncology. Venom-producing mini-organs Additionally, Puschhof and his colleagues developed snake venom gland organoids. These miniature organs are fully functional, meaning that they produce venom. The long-term goal is to use these organoids to produce antivenom and venom-based therapeutics. And if that was not enough for a successful PhD, he and his colleagues produced an atlas characterizing the different hormone-producing cells in the gut, which had never been done so thoroughly before. Best friends All projects undertaken by Puschhof are characterized by collaboration. “Collaborating in great teams and working with my best friends, those were the real highlights of my PhD. I have enjoyed the late nights in the office a lot, sitting together and thinking about the next cool experiment we could do.” Luckily, most of the lab work for his thesis was done before the pandemic hit. “Due to the corona-measures, I had much more time for writing my thesis than I anticipated.” Defense The ceremony took place in a digital form, meaning that Puschoff defended his thesis from behind his computer with only his paranymphs present. Others could follow the event via a livestream. That also had its advantages for Puschhof. “I have worked in labs all over the world and my family lives in Germany. With the livestream, I was able to share this special moment with all these people, who normally may not have been able to be there.” Now that Jens Puschhof obtained his doctorate, he will follow up on his discoveries in an academic or start-up setting.
