Towards a Quicker Diagnosis

Students who produce outstanding scholarly work are nominated for a semester award. In this series, we look at a few examples to show what makes an excellent thesis, how it can benefit teaching, what motivates students to produce outstanding work, and how they are supported and guided by teaching staff.

Children with a congenital immune deficiency cannot properly defend themselves against pathogens. In some children, the effects are so severe that they suffer from serious infections within their first months of life. Physicians often have difficulty recognizing these congenital immune deficiencies, as the symptoms often resemble regular infections. To complicate matters further, there are many different types of genetic immune deficiency, with a wide range of clinical symptoms of varying severity.

Medical student Marlene Münger is familiar with this problem. During her studies, she developed a keen interest in the human immune system. “I was amazed by how complex it is and how sensitive it is to genetic errors,” she says. The interactions between immune cells, and why the immune system incorrectly attacks the body’s own cells in the case of defects, is yet to be precisely researched, she noted. “That’s why I wanted to dedicate my Master’s thesis to this topic,” she explains.

Marlene Münger found a suitable supervisor in Jana Pachlopnik Schmid, professor of pediatric immunology at UZH. Her research aims, among other things, to make diagnosing congenital immune deficiencies easier. When Münger contacted Pachlopnik and asked her to supervise her Master’s thesis, her suggestion was well received. 

“I want to encourage my students to be curious, to develop new ideas, and to find solutions independently. Creating a supportive environment is very important to me,” says Pachlopnik. Münger adds, “Thanks to Jana, I felt like a fully-fledged researcher. I completely forgot I’m still a student.” 

During her research at the Children’s Hospital, Marlene Münger got to know the immunology team, while also learning about everyday clinical practice and working with sick children. “These experiences have motivated me a lot,” she says. “I was part of a team that worked every day to help sick children.”

She conducted comprehensive literature research for her Master’s thesis. From more than 1,500 scientific studies, she selected those that describe disease symptoms and identify congenital immune deficiencies. She then grouped the disease symptoms and assigned them to genetic defects. 

In order to review some 1,500 scientific articles on immune deficiencies, Marlene Münger organized a small team of five medical students who were still at the beginning of their studies to support her research. The Master’s student had a special responsibility. She had to introduce her assistants to the work, while also ensuring that the scientific articles were correctly understood and evaluated. “I remember that during summer we sat in a hot room in the Children’s Hospital, discussing the results for several weeks,” says Münger. 

As the person in charge, she supervised the medical students and also had to independently decide which publications were relevant, and which were not. When in doubt, she could always rely on her professor’s expertise. In the end, they chose 700 publications to focus on. “We analyzed these and applied the double verification principle,” reports Münger. The research took about nine months to complete. Thanks to an already established web application, she could then systematically compile the insights gained.

The analysis of the data yielded new insights: children with symptoms such as recurrent infections, skin rashes and autoimmune reactions were found to have genetic defects in the ARPC1B and WAS genes. Meanwhile, in cases of recurring fever and arthritis, mutations in the NOD2 gene are responsible. In her Master’s thesis, the student documented several other examples in which a cluster of symptoms was caused by defects in different, sometimes even functionally unrelated genes.

These findings could make it easier for doctors to reach a targeted diagnosis more quickly in the future, and to identify suitable treatment options, says Jana Pachlopnik. Marlene Münger approached her Master’s thesis with great care and exceptional organizational talent, which earned her a well-deserved semester award. The planned publication of her findings in a scientific journal will bring Münger further recognition for her work. 

Marlene Münger wants to remain in academia and in the immunology team at the Children’s Hospital. She would like to continue her work and has already started her PhD in order to deepen the findings of her Master’s thesis. “Research into congenital immune deficiencies is an ongoing process that still requires a lot of research,” says Münger. But with continuously improving diagnoses, she believes there is now more hope than ever for the children affected.