Students Experience Research Firsthand With Research Cycle In Genomics

How do students develop self-motivation? What is my own motivation for teaching molecular biology? During his CAS in University Teaching and Learning, molecular biologist and bioinformatics specialist Jonas Grossmann found himself preoccupied with these questions. Then he came across the research-based teaching and learning method, in which students take on the role of researchers and investigate questions they have come up with themselves. “My former colleague Lucy Poveda and I both loved the idea. We drew up a teaching concept and applied for a grant from the Teaching Fund,” recalls Grossmann.

Evolution of staphylococci
Grossmann works at the Functional Genomics Center Zurich (FGCZ), a joint facility of UZH and ETH Zurich that performs molecular biology analyses for research groups. “We have the latest technology at the FGCZ, but we don’t get to do our own experiments,” he explains. In SNSF professor and evolutionary microbiologist Rolf Kümmerli, they found their ideal partner to develop the Research Cycle in Genomics block course. The three researchers together designed an experiment to study how staphylococcal pathogens adapt to their environment. They exposed three bacterial strains of staphylococci to an extract in which their antagonists, the pseudomona bacteria, had lived and which contained their secretions. “The extract causes stress to the staphylococci. At first, they don’t grow as well as normal, but later they adapt,” explains Grossmann. The DNA of the stressed staphylococci and of the control groups that had had no contact with the extract were sequenced at the FGCZ twice: once at the start of the experiment and again after 15 growth cycles – approximately 250 generations later. This data set, which Grossmann and Poveda were able to create thanks to financial support from the UZH Teaching Fund, forms the basis of their research-based course. Students can use the data to study how the DNA of the staphylococci adapts in order to survive in the extract.

Painstaking detective work
“The unique thing about our course is that the students are the first to analyze this data,” says Grossmann. “That makes it even more motivating.” In the block course, advanced Bachelor’s students from UZH and ETH get first-hand insights into how research works. Over the course of three and a half weeks, they complete each stage of a classic research cycle: from developing a question, reviewing the literature and analyzing the data to presenting their results. “I didn’t really know about the research process before,” says biomedical student Aleksandra Misiek. She chose to enroll in the course because of her interest in genetics and looked forward to gaining practical insights from the block courses, having previously completed theory-based core modules.

During the first week, after an introduction to the topic, the students read up on the subject and work in pairs to formulate an initial research question. In the second week, they are given access to the data of the 150 analyzed genomes. They then need to try to narrow down and answer their question by analyzing the data alongside the literature in an iterative process of repetition and refinement. They use computer programs to compare the genomes and identify relevant changes. With the help of literature and specialist websites, they can then find out which protein is encoded at a transcribed DNA site and what its function is. “The students have to skim read a lot of scientific papers in a short period of time, and learn to pick out the most important information,” Grossmann explains. Misiek particularly enjoyed the research work: “It was interesting to experience research away from the lab for once,” she says. However, she found coming up with a research question on her own a challenge, as was processing the large amount of new information. “In lectures, we are simply told what happens if a specific protein doesn’t work. But finding this out for yourself is no mean feat,” says the budding researcher.

Diving in together
Jumping in at the deep end is part of Grossmann and Poveda’s teaching philosophy. “We believe that students learn more when they have to figure out the route for themselves, and that includes making mistakes along the way,” says Grossmann. He sees himself as a coach who motivates the students and shows them that there’s always another way, even if they hit a dead end. At strategically important points in the process requiring particular skill, he and his teaching partner Natalia Zajac provide expert tips to support the students’ own learning. They also meet each group regularly for progress reports, in which the students present the status of their work and get to ask questions.

One aspect that has proven difficult for students is learning new programs such as the Interactive Genome Viewer, which is used to evaluate DNA changes. “We tried to help each other with this,” recalls Misiek. Grossmann and Zajac also created a WhatsApp group for the students and teaching staff to communicate, highlight interesting papers or share useful tips and tricks. “Research today is interactive and collaborative,” says Grossmann.

Flexible work with concrete results
The way the course is managed also gives students a lot of leeway in how they organize their work: there are few fixed deadlines and the groups mostly work at times that suit them, either at home, on campus or on the FGCZ premises. Misiek particularly liked this aspect: “I learned about how I work best.” Meetings can be done in-person or via Zoom. “We developed the course during the pandemic, so this hybrid mix works well,” says Grossmann.

Despite the flexibility, he does expect concrete results by the end of the block: the students write an abstract and present their findings in a poster session at a mini-symposium where Kümmerli and his doctoral student ask critical questions. The idea for this setting also came from the real world of research, where it is customary to present research topics at conferences using abstracts and posters. “It feels like being in a research group with different graduate students working on one overarching question,” says Grossmann.

Possible survival strategies of staphylococci
Grossmann has delivered the block course three times so far. “It’s fascinating, each cohort has found new questions to research,” he says. There have also been some groundbreaking discoveries: one group discovered that some staphylococci in contact with the extract cease production of a protein which imports amino acids into the cell. “We assume that the pseudomonas released the amino acid called selenocysteine into the extract, and that this is toxic to staphylococci,” Grossmann explains. If staphyolococci switch off the amino acid importer, the toxic substance cannot get into their cells. To test this thesis, the course leaders are now conducting follow-up experiments. “With the new data, we can make the course even more interesting,” he says. The chance that these findings could one day contribute to a specific treatment for staphylococcal infections is low, according to Grossmann. “However, wonderful parallels can be drawn between the evolution of staphylococci and coronavirus mutations,” he says. On the final day of a previous course, he therefore set up a hackathon in which students had to find out as much as they could about the then-new Omicron variant. As for Grossmann’s own motivation? When he talks it is clear: it comes from seeing students independently immerse themselves in a subject matter and then knowledgeably and skillfully conduct their own research.