Sunday, July 2nd
For most of us, our trip started on Sunday at Utrecht Central Station at 12.30 in the afternoon. We all managed to catch the train and after some struggles to find and to claim our seats (not all travellers can read their tickets as well as we can, apparently), everything went well. When we arrived in Heidelberg about six hours later, our first sight of the city was a little bit disappointing. Our hostel appeared to be located in an industrial area near the station. However, the rooms were big and comfortable. After a short time to settle down, we went out for dinner. The half an hour walk was definitely worth it. An ‘all you can eat Flammkuchen dinner’ was waiting for us and together we shared several kinds of Flammkuchen, a typical German dish that looks like a combination of a pancake and a pizza. Afterwards, we went back to our hostel for a good night’s sleep to get ready for the next day. Written by Jacqueline van Eck.

Flammkuchen: all you can eat – making some hard decisions!

Monday, July 3th
We woke around 7.45 AM and we had decided to eat our breakfast in a bakery next door. Some enjoyed a sandwich and others a croissant accompanied with some coffee or tea. Slowly conversations started and it was enjoyable to sit in the bakery with many locals around us. However, the bakery was quite expensive, so, unfortunately, we could not go there every morning. We took the bus to the campus of Heidelberg. On campus, we would meet Victor Winter, the masters’ coordinator of the Life Science faculty, and we would also meet some of the master’s students. They introduced us to Heidelberg University and the student life in Heidelberg. The students took us on a tour of the beautiful campus of Heidelberg. We saw the new Mathematikon building, the hospital, the various DKFZ buildings, different faculty buildings and the Botanical Gardens. The tour ended at the Mensa, where we had a lunch with the students and masters’ coordinator. During our informal lunch, they taught us which bars we needed to visit in the evenings, but we also spoke about women-men percentages in science and the differences between the Netherlands and Germany.

In the afternoon we took the bus to EMBL, the European Molecular Biological Laboratory. After a few minutes, the bus started to make some hairpin turns. The EMBL is located in the hills near Heidelberg, a beautiful location, definitely worth the bus trip! At the EMBL, the project of Dr. Anne-Claude Gavin was presented to us. In this project, they aimed to find proteins that are expressed differently in hematopoietic stem cells during different stages during ageing. Marco Henrich explained how they try to create knowledge about the effect of ageing on stem cells. For this different techniques are used. After a presentation and a question session, it was time for a tour through the core facilities of the EMBL. The sequencing core facility had a very enthusiastic professor who explained the history, methods and mechanism of sequencing. We learned that Sanger is one of the few people that has received two Nobel Prizes. Only after he handed us all an Illumina flow cell and the PhD student told him we really needed to move on he would let us go. The core facility of mass spectrometry was waiting for us.

The mass-spec supervisor showed us around and explained the techniques. Fun fact: the spectrometers were named after Bert and Ernie from Sesame Street. The core facilities were quite beautiful and extensive. All the labs and research groups of the EMBL could use these facilities. Afterwards, we went to the ATC-building on the EMBL Institute. A beautiful building that looks like a DNA-helix. Outside there was a large G built; the missing G of the ATC-building to complete the genetic code. On the rooftop of this building, we enjoyed some Kaffe und Kuche and the view over the surroundings of Heidelberg. Then we took the bus back to the city and we had dinner at Urban Kitchen. Written by Geke Poolen.


Walking the stairs in EMBL

Tuesday, July 4th
The day started with an outdoor breakfast in the parking lot of the hostel around 9.00 AM. Afterwards, we made our way to the company BioRN, a networking company that connects startups with investors. In a creatively designed room, we listened to a presentation by Brigit Rogell. She told us about the history and the goals of BioRN. The company is involved in many networks of companies, cities and universities and aims to connect startups with the right investors and to create a short link between the academic and the corporate life. After the presentation, we had an open discussion, which also included Brigit telling us about her person life-path and choices she made to get where she is now.

After lunch, we visited the first DKFZ (Deutsches Krebsforschungszentrum) location of our trip. The DKFZ is an organisation that focuses on cancer research and has multiple locations and laboratories throughout Heidelberg. Here, we were welcomed by prof. dr. Stefan Eichmüller, who introduced us to three of his PhD students. David Eisel was the first to present his research to us on adaptive T-cell therapy to treat cancer. Macrophages can be divided into two subtypes, M1 and M2. M1-like macrophages stimulate the immunoreaction and suppress tumour growth. M2-like macrophages, on the other hand, have immunosuppressive properties.  The aim of this study was to activate CD4+ cells, to induce IFN-γ production. The IFN-γ would induce a shift from M2-like macrophages to M1-like macrophages, leading to immune stimulation and tumour suppression. Antonie Pone was the second PhD student to present on his study, his work focused on identifying miRNAs that influence if melanoma cells are recognised by tumour antigen specific CD8+ T cells. He transfected melanoma cells that express the antigen TRP-2 with a library of miRNAs and researched if the TRP-2 expression changed due to the miRNA expression. He also investigated antigen recognition and tumour cell killing by using TRP-2-sensitive immune cells. He explained multiple techniques that can be used to study this, including the IFN-γ ELISA spot assay, the CELLigence assay and the luciferase high-throughput assay. So far, he has managed to develop a method to test the library of miRNA in the first screening round.

Afterwards, Theresa Kordaß led a computer practical, designed especially for our visit. This exercise taught us the basic principle of in silico miRNA research tools that can be used to select for miRNAs as biomarkers. It was very instructive, well made and the instructions were clear. We were overwhelmed that she had made this instruction especially for us and we enjoyed it very much.

When the last visit for that day had ended, we could finally enjoy the beautiful weather outside as we walked our self-guided tour of the Heidelberg old town. Some students had prepared a small piece of interesting sights in Heidelberg old town and this way we also got to know Heidelberg a little bit better. This way we learned that Heidelberg had a student prison where students who misbehaved, mostly meaning that they were too intimate when they were not married or when this was not allowed, were locked up. But over the years this became a place to go when you needed a good reason to skip class and you were even allowed to invite your friends there. We also walked past the Old Bridge, the corn market, the Jesuitenkirche and many more sights. In our city walk, we also included Heidelberg Castle, which we had often seen during our travels through Heidelberg, as it lays well above Heidelberg and oversees the city.

That evening we had dinner at Palmbräu Gassa in the centre of the old town. This restaurant serves typical local German dishes and good German beer. Written by Alice Driessen.


The students working hard during computer seminor given during the visit to the group of Stefan Eichmüller

Wednesday, July 5th
We started the day with a visit to the Department für Infektiologie of the Universitätsklinikum Heidelberg, where we visited a research group concerned with malaria. Their group leader, Professor Michael Lanzer, kicked off the day by giving us a small overview and introduction into parasitology. Thereafter, three PhD students working at the lab shortly presented the aim of their research. Britta Nyboer started by giving an introduction in malaria and its causative agents, before delving into her research about the use of mouse models for malaria. Subsequently, Monika Jankowska presented her research which was aimed at the mechanisms by which the malaria parasite increasingly achieves resistance against anti-malarial drugs. Finally, Maëlle Duffey gave us a general presentation about the process of developing new drugs, which she further elaborated on through an example of the drugs they designed for malaria (which are still in development). Our visit to the Malaria research group was finished by a tour through their research facilities, which included a talk about the diagnostics department entirely in German.

In the afternoon we visited the Proteomics of Stem Cells and Cancer group located in the German Cancer Research Center (DKFZ). The group leader, Professor Jeroen Krijgsveld, started by going through the main challenges associated with the use of proteomics in research. Next, we received a tour through the lab facilities. This was followed by presentations by Vanessa Todorow, Jakob Trendel and Gianluca Sigismondo, who are are a bachelor-student, PhD-student and Post-Doc working for the research group, respectively. Their research was mostly marked by the use of proteomics techniques for different purposes. Vanessa, for example, uses proteomics to research and compare the protein profiles of pluripotent stem cells differentiating into neural cells to neural cells switching back to stem cells. On the other hand, the research of Gianluca was aimed at the protein-protein interactions of transcription factors in the event of DNA damage. Finally, Jakob identifies proteins that bind to RNA during oxidative stress.

After a day full of lab visits and interesting presentations, it was time for some relaxation. With the beautiful Heidelberg weather, some chose to go to a terrace, whereas another group went to a park next to the Neckar where a couple of people even decided to go for a refreshing swim. We met up again with the entire group at the Vetter’s Alt Heidelberger Brauhaus for dinner. At this beer brewery, the beer formerly known as the worlds’ strongest beer was enjoyed. Written by David Binyam.


One of the many unsuccessful attempts to create a complete group picture. Neckar view.


Thursday, July 6th

At 8 AM, we had breakfast at the hostel. After that, we went to Bioquant at the University of Heidelberg. First, we had a lab tour by a PhD student and a postdoc. Next, we had an introductory lecture by Dr. Dirk Grimm on the use of viruses in therapy. His group focuses on adenovirus-associated viruses (AAV), the CRISPR-CAS9 system and RNAi, in order to use AAVs for gene therapy. AAVs are non-toxic and very small viruses that are carried most people. It falls under the category of dependoviridea and needs the presence of an adenovirus for its own replication. AAV is used for therapy for different targets, like HIV and HBV. Special characteristics of AAVs are its wide tropism, as it can infect many tissues, and its site-specific DNA integration, which makes it an interesting vehicle for gene therapy. The research of this group is focused on the improvement of this vector. They hope to lower the immunogenicity of the virus, to prevent the human body from eradicating the virus before its goal has been achieved, and to increase the efficiency of infection and DNA integration for the improvement of the efficacy of the therapy. To this end, they combine several genetic techniques such as DNA shuffling, randomized PCR for the introduction of mutations and capsid evolution. After the talk from Dr. Grimm, Janina Haar (PostDoc) told us something about her career and her own experiences. One remarkable thing she said about studying and doing a PhD is: ‘The statement ‘don’t have gaps in your CV’ is bullshit. Take your time to decide what you want.’ According to Janine Haar, you have to be able to justify your decisions and think about why you want to do certain things. After the talk, we had some drinks and snacks with the group members and we started our tradition of asking the PhD students whether they were a happy or a sad PhD student. Furthermore, they told us to always talk to lab members without the presence of the group leader to really get a feel of the atmosphere in the group. Then, we had lunch at a bakery on the campus and we walked to the DKFZ.

At 2.00 PM we started with a talk from Marieke Essers. She is group leader from the Junior group ‘Stress-induced activation of hematopoietic stem cells’ from HI-STEM (and interestingly, she used to be a board member of our very own study association, Mebiose). Tumors contain stem cell-like cells that can cause a relapse if some of them remain after treatment. By targeting those cancer stem cells (CSCs), you can eliminate the whole tumor. Essers group looks at hematopoietic stem cells (HSCs) in the context of inflammation (stress). The environment of the HSC is very important for its function. Under inflammation, mature cells are activated and the proliferation of progenitor cells is blocked. IFNa is produced upon inflammation. This has an antiproliferative effect on hematopoietic cells. Essers’ group examines the effect of IFNa on HSCs. Stem cells become activated after treatment with IFNa. HSCs sometimes form colonies that already have made a commitment. Without a niche, HSCs do not respond to IFNa. IFNa leads to more blood vessels that are more permeable in the bone marrow. HSCs produce VEGF in response to IFNa. VEGF leads to the activation of endothelial cells. The research of HI-STEM is also focused on the development of therapies. Stem cells are often resistant to chemotherapy. Essers’ group examines whether IFNa is a possible ‘drug’ to target CSCs. In Chronic Myeloid Leukemia (CML), the BCR-ABL fusion gene can be targeted specifically. But CML patients often have a fast relapse due to remaining CSCs. With IFNa, you can activate CSCs in CML, and then the CSCs can be targeted with the specific drugs as well.

After the talk of Marieke Essers, we had a discussion with PhD and master students from the group of Essers and Sprick (another group leader from HI-STEM). A tip from the students is to talk with people in the lab when you are choosing a PhD position. A question you can ask the people in the lab is whether they lunch together. This gives an impression of the ambiance in the group.

Then we had a talk from Martin Sprick, group leader of the group Stem Cells and Metastases. His presentation was on the transition from Bench to Bedside. The talk was focused on pancreatic adenocarcinoma (PDAC), a disease for which only a single treatment is available even though it is a heterogeneous disease. Martin Sprick explained how their research, based on the three known subtypes of PDAC based on gene expression, could link these subtypes to pathological stainings of tissue biopsies. His hope is that the knowledge of the various subtypes in patients can aid in optimizing the treatment for each specific patient.

After the talks the DKFZ, we had some free time in which some of us went to the Neckar and others stayed at the campus. We had dinner at the campus at 7 PM at the BräuStadel, where the employees wear traditional clothing. Then we went to the old city to eat a McFlurry and drink some cocktails, joined by one of the students that we met on our first day. Written by Anne Borst.

Discussing master programs, internships, and PhD tracks with some students currently working in the labs of Marieke Essers and Martin Sprick. Every one of us learnt some tips for making decisions on our future! And, most importantly, this visit included some excellent snacks.


Friday, July 7th

The last day of our foreign excursion would turn out to be a long one. Before I’ll talk about the not so perfect journey home, I will summarize the two lab trips of this day. In the morning, a bus trip up the hill took us to EMBL again; this time to the group of Rainer Pepperkok. We started off with a short talk about fancy microscopy techniques including super resolution microscopy, after which we were shown around the microscopy lab. Fun fact: the most expensive microscope costs over a million euros. A nice feature of some of their microscopes is automated analysis: for example, the microscope can be instructed to automatically zoom in on and monitor dividing cells. The group of Pepperkok works a lot with such imaging techniques, mainly with fluorescence microscopy. Although Pepperkok himself was not able to join us, two of his group members gave some interesting talks about their research in a lecture room with extremely comfortable seats and air-conditioning (very welcome in the hot summer weather).

The first lecture was about cholesterol and cardiovascular disease. Part of their research focuses on identifying new components of the cholesterol endocytosis pathway. Furthermore, the effect of several genes associated with cardiovascular disease on cholesterol regulation is being tested. In the second lecture, we learned about their investigations into Golgi biogenesis. Evidence suggests that the Golgi apparatus is synthesized de novo, contrary to earlier beliefs that the Golgi cisternae are fixed structures. A cool technique named laser nanosurgery is used to deplete the Golgi from cells, after which de novo Golgi biogenesis can be detected with time lapse imaging. We ended our visit with a discussion on doing a PhD or going into industry. After joking that happy PhD students do not exist, it was concluded that it depends on your personality whether you should work in academia or in the industry.

 We spent the afternoon with the group of Jan Siemens on thermoregulation. First, we heard about specific warmth sensitive neurons that increase their firing upon a rise in temperature. Interestingly, this research was conducted using capsaicin, a compound that causes red peppers to be hot, to simulate an increase in temperature. Trpm2 was found to be an ion channel involved in this response. Next, the relationship between the deep brain temperature and the core body temperature was discussed. The second talk was about the use of human embryonic stem cells (hESCs) in their research. Since sensory neurons are very diverse and individual subtypes are difficult to isolate, they generated neural crest cells from hESCs and differentiate them further into sensory neurons. After characterization of the differentiated neuron, functionality can be tested. The talk was interrupted by the timer because we had to leave on time to catch our train.

We arrived at the station almost an hour early, but our first train was already delayed by 30 minutes. After this went up to 60 minutes, we decided to take the train to Mannheim and catch another train to Frankfurt; otherwise, we wouldn’t catch the ICE to The Netherlands. As if we weren’t stressed enough, this train got delayed while we were in it. The conductor called the ICE to say that we were coming, but this was not of any help: we sprinted towards the ICE but missed it by approximately ten seconds. Since no trains were going to the Netherlands by this time, we went to Düsseldorf where we could stay in a hotel for free if we wanted. However, several parents were prepared to drive to Düsseldorf and pick us up. Parents, thank you so much for saving us!  Written by Welmoed van Zuiden.

 

(1) On Friday, it was Jochem’s birthday! And that means cake for breakfast.
(2) A long journey home.