Exploring the aging process – Daniel Stähli wins award for the best master’s thesis

Daniel Stähli had a great time at Stanford, where he wrote an outstanding master’s thesis.

Daniel Stähli has won the award for the best nanoscience master’s thesis in 2019. He wrote his excellent thesis about aging processes in the blood-brain barrier at Stanford University (Palo Alto, California, USA) in the laboratory run by Professor Tony Wyss-Coray, one of the leading researchers on the subject of aging. In his nine months at Stanford, Daniel not only had the opportunity to work with numerous scientific methods, but also came to appreciate his colleagues’ optimism, enthusiasm and openness. Spending time in California was the perfect way to conclude his studies in nanoscience – a subject he would definitely choose again.

Interested in nanoscience from an early age
Even as a child, Daniel Stähli knew he wanted to be a scientist, and he continued to be fascinated by the sciences at the Kirschgarten high school in Basel. His decision to study nanoscience was prompted by the “Journey Through Worlds” (Weltenreise) event, in which the University of Basel takes visitors on a journey from the cosmos into the nano world. “I went to the “Weltenreise” at the Schauspielhaus theater in Basel with a fellow student. That was when we first heard about the interdisciplinary nano degree program. It sounded exciting and modern,” Daniel recalls. They both went on to study nanoscience in Basel.

Project work and master’s thesis were the highlights
Daniel found the bachelor’s program to be fairly “jam-packed” and challenging, but also extremely educational. Looking back, he sees it as the ideal preparation for the subsequent master’s program, which was much more his style. “It was great that the master’s program allowed us to study three different areas in much more depth through two projects and a master’s thesis. We were free to choose our subject areas and were given the support we needed to gain experience abroad,” he says, summarizing what he believes to be the most positive aspects.
In his first project, which he completed at the Department of Biomedicine in Professor Daniela Finke’s laboratory, he studied the differentiation of stem cells and lymphocytes, which play a key role in tissue immune responses. In his second project, Daniel used an SNI travel grant to spend three months at the International Iberian Nanotechnology Laboratory in Braga (Portugal) with Dr. Pieter de Beule. Here he focused mainly on programming and statistically analyzing fluorescence microscope analyses of membrane proteins.

Success on his own initiative
Daniel knew that he wanted to go abroad for his master’s thesis too. He was particularly interested in research on aging, so he searched the internet for research groups working on this topic. Professor Tony Wyss-Coray of Stanford University (Palo Alto, California, USA) is one of the experts in this field. He proved that transfusing plasma from young mice has a rejuvenating effect on older mice.

Daniel wrote to him and was quickly accepted. “However, spending time abroad like this involves a huge amount of administration, particularly if you want to go to the USA,” he comments. Daniel first made contact in February 2018; he received confirmation from Stanford University in July and travelled to California in October for nine exciting and intensive months.

“We have been thoroughly impressed by Daniel’s passion and dedication to science and his aptitude for experimental research. We would have loved to keep him longer.”

Professor Tony Wyss-Coray, Stanford University (Palo Alto, Kalifornien, USA)

 

Role of the blood-brain barrier in the aging process
Daniel’s master’s thesis concentrated on the blood-brain barrier and its protein permeability. The blood-brain barrier is a selective barrier that shields the brain from the rest of the body and regulates and restricts the absorption of plasma proteins. It is formed of endothelial cells with the aid of pericytes and astrocytes. As a person grows older, and in cases of neurodegenerative diseases such as Alzheimer’s, the barrier’s extreme selectivity decreases and various substances can enter the brain that are not detected in young, healthy brains. It is important to know precisely how the blood-brain barrier works when treating neurodegenerative diseases – if the blood-brain barrier is intact, it also prevents therapeutic antibodies from getting into the brain.

Daniel investigated how the blood-brain barrier changes with age. Together with his supervisor, Andrew Yang, he developed a new method to test the permeability of the blood-brain barrier and examine the normal aging process of the blood-brain barrier in mice. First, they marked all proteins in the blood plasma. Then they studied which of these proteins were detected in the brain cells and in the endothelial cells that make up the blood-brain barrier.

They identified certain genes that support the absorption of plasma in the endothelial cells. The results showed that numerous proteins were able to pass through the blood-brain barrier. In young mice, these proteins are absorbed via specific receptors; in older mice, they do not have a specific route.

On the whole, however, the absorption of plasma proteins does not increase, but actually tends to decrease. Daniel was also able to show that the number of pericytes – one of the cell types that make up the blood-brain barrier – decreases with age.

His work not only proved which processes are triggered by the aging process, but also which proteins can break through the blood-brain barrier. In the future, these proteins could potentially be used as shuttles for therapeutic agents.

Daniel succeeded in detecting calcifications in the brains of ageing mice. (Image: Daniel Stähli)

Unique experience
Daniel’s nine months in Palo Alto were very special, and he wouldn’t have missed them for the world. “I was very lucky to have such a good supervisor in Andrew. We worked a lot and extremely hard, but it was a great and exciting time.” His (now award-winning) master’s thesis wasn’t his only crowning achievement – his data also contributed to a paper by the team that has just been accepted for publication in Nature.

Daniel’s lab colleagues were instrumental in making his experiences so positive. He was impressed by the optimism, energy and openness with which he was received by other doctoral students, postdocs and professors. “The whole Bay Area has a hugely motivating atmosphere. It is densely packed with excellent universities and leading life science companies. They work closely together, have tremendous resources at their disposal and anything seems possible,” he remarks. Daniel wasn’t the only one to be impressed. Tony Wyss-Coray, his supervisor at Stanford, speaks very positively of Daniel’s dedication and performance: “We have been thoroughly impressed by Daniel’s passion and dedication to science and his aptitude for experimental research. We would have loved to keep him longer.”

The next step – a doctorate
However, Daniel will probably stay in Switzerland for the next stage of his scientific career. After six months of civilian service – which he is about to complete – he would like to begin a doctorate, and is looking at various groups at the University of Basel, ETH Zurich and EPF Lausanne. He would like to pursue his interests in various fields of life science.

A good decision
Looking back, he is glad that he opted for nanoscience seven years ago. He still values the wide range of experiences he has been able to gain – not only in various subject areas, but also in different countries thanks to support and funding from the SNI, the University of Basel, the Freiwillige Akademische Gesellschaft and his parents.

And the degree program didn’t just enrich his subject knowledge. “I have made many good friends,” he comments. His work on the executive board of the Association of Nanoscience Students at the University of Basel has certainly helped him to establish numerous contacts and view his time as a student in such a positive light.

We congratulate Daniel on his excellent and fascinating master’s thesis and wish him all the best for the future!

 

Further information

Wyss-Coray research team

Publication in «Nature»