Epigenetics for all

If you would like to get to know the researchers of our community, check out the interviews.

Mrinmoy Pal (PhD Student; Torres-Padilla Lab) about why he decided to become a scientist, how he got fascinated of Epigenetics, and why he moved to Germany for doing his PhD, even though most of his fellows went to the US.

Mrinmoy Pal obtained his integrated Master’s degree at the Indian Institutes of Science Education and Research (IISER), Kolkata. After doing several internships at the Indian Institute of Science in Bangalore, the CSIR-IGIB in Delhi and the University of Göttingen, Mrinmoy performed his Master’s thesis in Sanjeev Galande’s laboratory in IISER Pune, where he focused on the role of histone methyltransferases during regeneration in Hydra. Mrinmoy joined the Torres-Padilla Lab in 2019. In the interview, he tells us why he decided to become a scientist, how he got fascinated of Epigenetics, and why he moved to Germany for doing his PhD, even though most of his fellows went to the US.

Hi Mrinmoy, thank you so much for taking the time. Can you please tell us a little about yourself and your PhD project?

I was born, raised and schooled in a small town called Bankura in West Bengal, India. I completed my Integrated Masters majoring in Biology from the Indian Institute of Science Education and Research (IISER) in Kolkata, which is 250 km away from my hometown. How does a single cell give rise to the entire human body? I was intrigued by this question ever since I was introduced to the basic concepts of genetics in high school. Through the course of my University education I grew interest in understanding the epigenetics mechanisms of early development and that’s why I decided to join Maria-Elena’s lab here at Helmholtz. Of course, the Bavarian beer made the choice of Munich as a PhD destination only easier. Since I started here in January 2019, I have been trying to tackle a rather fascinating question: How is DNA packaged for the first time ever and what is so special about this organization of the nucleus at the beginning of life, that one cell is powerful enough to form a full organism? 

Was it a childhood dream to become a scientist?

Science yes but scientist? Not really. In the kind of Indian middle-class family like mine it is the dream of everyone that the kids become either a physician or an engineer. These are the two most reliable options for ensuring sustainable income for a family in India. So, in high school, if the kids are good in mathematics and physics, they are conditioned to aspire to become an engineer. And if the kids like Biology in addition, then they should try to become a physician. Almost all my relatives from my mother’s and father’s side are still into farming and me, my brother and my cousins are the first generation of completing proper University education. All the relatives and peers also wanted to have a doctor in the family, because then it becomes much easier to get the references to go to specialist and there is always someone who can take care of them. Since I really liked Biology, I was supposed to become the first physician in the family and I also wanted it.

How did you end up in Science then and how did your parents react?

That is actually an interesting story. It has a lot do to with my brother’s career choice and new governmental policies that were initiated to catch more good students for the basic sciences because they usually studied engineering or medicine. Since long, we didn't have really good national institutes that give science and research a platform. Through this initiative, we have now seven Institutes of National Importance, which are spread across the bigger cities of India, such as Pune, Mohali, Bhopal as well as the IISER in Kolkata. Despite aspiring to become an engineer initially, my older brother decided to study basic sciences. He went to the oldest research institute in India, the Indian Institute of Science (IISc) in Bangalore which had also only recently started undergraduate program in science. This opened my eyes to also considering studying basic science and research as an option. I saw how his exposure was and how really research is done to address more fundamental aspects of science and technology. Beforehand, it was not very clear to me or the student community in general, what doing science in a really good institute meant. In his first year of studies already he could attend conferences with Nobel Laureates giving talks and this was truly inspiring. And seeing him experiencing all that, I got really fascinated and decided that science would be also a good choice for myself and my career. So, even after getting admission into the finest medical colleges in Bengal, I opted to go for basic science and decided to join IISER Kolkata.

My father took it well. My decision was not a problem for him. My mom was also happy that I chose what I wanted to do, but I think it took her some time to process my decision. Also, my relatives and peers were a bit upset at the beginning that I won’t become a physician. But I am only thankful to my family for allowing me to make a decision on my own which, to be honest, in Indian middle class families is not very common.

How were your student days at IISER? 

I started to study in 2013 and my class was the first one moving to the new campus, which is actually 60 km away from the Kolkata. All the big national institutes need much space for a big campus, because all the students live together with their faculty and the staff members. So, the space, around 200 acres, is mostly required for housing and the laboratories. When we entered, the campus was completely empty. There were just the hostels and we had to bike to the other transit campus to do the classes, and then to the practicals on the other campus. In our first year, the lecture-hall were just above the canteen and for the first two terms, we didn't have WIFI. We had to go to the computer center to submit our assignments. But now, everything is there and state-of-the-art. The campus developed with us. We could see the journey of the institute in front of our eyes.

In the first study year, we had courses on mathematics, physics, chemistry, biology, computer science, as well as earth sciences (geology) and in the second year, we had to choose three pre-majors out of them. In the third year, we had to decide in which subject we want to specialize. I chose biology, obviously.

In general, there was always an emphasis to provide students with hands-on experience in the lab. For example, in biology, we learned how to do SDS pages, molecular cloning, and protein purification already in second year of my undergrad. This was really a privilege for us. At a normal university in India, the resources and funding are so limited, that the students cannot always touch a pipette and do hands-on experiments.

How did you get fascinated by Epigenetics?

So, to be able to study at IISER, I needed the KVPY fellowship (Kishore Vaigyanik Protshahan Yojana), which is for good students in science to pay the university fees, rent, living expenses etc. To continue this fellowship, you had to do internships and hand in reports about your studies and experiences. So, by giving you the fellowship, they're pushing you to work more in science because every summer, during the three months break, when normal students will go home and enjoy the time with their families and friends, you have to go to another city, if you like, or even in the same Institute to work and take part in research activities. After finishing my first year, in the summer, I worked in a lab in IISc Bangalore on tuberculosis and in the next summer I went to IGIB Delhi to work with nanoparticles and gene delivery. Additionally, in the second year, I did a semester project working on the behavioral biology of honeybees. So was really exploring different things.

In journal clubs, I heard about Epigenetics and I found this topic really fascinating. Then I took a course in Epigenetics offered by Sanjeev Galande, who was one of the big names in epigenetics in India. The course was actually through a virtual platform and we were attending the classes from Kolkata in front of the screen. This course showed me that Epigenetics is what I want to work on. Because of my interest, I interacted a lot with Sanjeev during the course and so, I asked him whether I can join his lab. Where I eventually ended up for my Master’s thesis.

Why did you come to Germany for your PhD?

In my third year, I came to Göttingen to Steven Johnsen’s lab through an exchange program of the DAAD. This fellowship is for Indian undergraduate students to come to Germany and to do research in a host lab. This was really a great experience for me, both scientifically and personally. We were like 50 students coming from all across India to Germany for three months. You could travel within Germany or through Europe on the weekends and during the week you were working in the lab. Working in Steve’s lab was really cool. It was a diverse group of passionate scientists and there was no hierarchy in the lab. So, basically the international environment in Germany, given along with the opportunities of travel and the lifestyle made me think that Europe can also be a good opportunity to do a PhD. Normally in India, the majority of the students want to go to US for their PhD.

Really? Why do you think this is the case?

First of all, the international reputation of European universities is not comparable to the one of Harvard, MIT, Stanford, Princeton, Caltech, etc. So, the students are not always aware that there are great opportunities in Europe for doing a PhD, such as in EMBL, Max-Planck-Institutes or Helmholtz Centers. Moreover, it is really confusing for Indian applicants that the PhD in Europe takes only three years, as it is stated in the job ads. In India, a PhD takes much longer and you do some teaching and lab rotations to find the perfect lab for the PhD. The US has a similar system, whereas here you go directly to the lab and you don’t know really if it is a good fit. If after a few months, you realize that it's not working out, you don't have a visa, you need to go back to India, you apply again. You lose a year, and you lose money. Coming abroad is often financially very difficult for a lower middle-class family like mine, because you have to pay the visa fees, get the flight tickets, pay the housing deposit to begin with and if it turns out after a few months that it doesn’t work out in the lab, you may get in trouble financially as well.

So, taken everything together, doing a PhD in Europe is kind of a black box for Indian students. But in the US, it's a graduate program. You don't even have to say specifically what topic you're interested in for your thesis. You go there, you chose your labs for the rotation then you see how it works. So, it's much more secure from a point of an applying student.

What can be done to change this misconception?

In the US universities, you have many different professors in one big department and everything is under a broad umbrella. You can choose from a plate, so to say. Whereas in Europe, for example at a specific Max-Planck-Institute, you have only 10 but very specialized labs. So, for Europe, you have to be really aware of what topic you want to choose for the PhD. This is actually what I tell my juniors. If you are not sure, what field exactly you want to work in after your Masters then go to the US. And if you have a clear idea already about what kind of question you want to address in your PhD, then Europe is a good place because you can find good labs who specialize in these topics. You can directly write to them, get in contact with the PI and discuss application procedure and funding opportunities. 

Last year, I went to the alumni meeting at IISER Kolkata and I collaborated with some of my friends who are doing their PhD in the US to show the current students the two perspectives. Even in Europe working in experimental biology you hardly complete thesis in 3 years and in most of the cases your funding and work contract is extended to make sure you finish the project and publish. I think more initiatives like this are important to clarify the misconceptions. Of course, DAAD is already doing a great job. They have ambassadors, who give talks at the universities. But I think there are more efforts needed from the people who came to Europe and did well during their PhD to share their experiences with the aspiring applicants. And yes, if European institutes want to attract more Indian students, they also have to provide them a platform to clarify these misconceptions. I am not sure whether the issues we discussed about are really clear to the Helmholtz Centers, Max-Planck-Institutes or other European research institutions. 

One last question. You are in the ChromDesign Innovative Training Network funded by the Marie Skłodowska-Curie actions. How has been your experience so far in the network?

Wonderful. The Network consists of 13 labs all across Europe who are working in different aspects of the 3D chromatin architecture. This has given me an opportunity to meet, discuss and collaborate with some of the pioneers in the field. In the pre-corona days, we had a kick-off meeting in Copenhagen and that was followed by a two-week winter school in CRG and ELISAVA in Barcelona. We did hands on training in genomics techniques, microscopy, bioinformatics and data analysis. Post-corona, we have not really had any opportunity to meet up in person but this did not stop our training courses. We participated in a Research Integrity and Science Ethics course recently, all in virtual platform. I would specially like to mention about the unique experience in the science communication course organized in ELISAVA. We tried to communicate our science to the artists and graphic designers. We could not use scientific jargons and technical details and still convey the research we are doing. In the end, we even had to walk into the La Rambla to talk to tourists and common people to communicate our science. It really was a challenging but fun exercise. I think as scientists we have the responsibility to bridge the gap to the society. If nothing, this pandemic has made that clearer than ever!

Dr. Wouter Koolhaas (EpiCrossBorders Coordinator) about why he became our Research Coordinator, the projects he is responsible for, how a good application should look like, and how it is to work from home office with two kindergarten kids at home.

Wouter is the Coordinator of our research school program 'EpiCrossBorders'. To his key responsibilities belong the management of the program curriculum, activities and events. This includes the international selection and recruitment of students, development and implementation of the Training Program. Moreover, he takes care of the EpiCrossBorders Website management and he is the approachable person to support the students. In the interview, he talks about about why he became our Research Coordinator, the projects he is responsible for, how a good application should look like, and how it is to work from home office with two kindergarten kids at home.

Wouter, you are our research school coordinator. Can you please tell us what you did before and why you decided to become a research school coordinator?

Before I started as a Research School Coordinator at the HMGU, I did my PhD at the Max Planck Institute for Biochemistry in the lab or Dr. Frank Schnorrer. There, I worked on Drosophila genetics. The goal of my project was to alter the stiffness of the flight muscles and assess how this affected the flight performance of the flies.

Looking back on my PhD, there were moments I really liked working on my PhD, but also many stressful and frustrating moments. My PhD project itself was very challenging. During this time, I learned a lot about myself, my strengths and my weaknesses. And then in the last year of my PhD I realized that it would be better for me to not pursue a career as a scientist. However, I still wanted to remain affiliated with academia.

I found the advertisement for the job as a coordinator of the Epigenetics Research School at the HMGU. This immediately drew my attention because it would allow me to remain affiliated with academia and I would be able to use my own PhD experience to support new generations of PhD students, and help them be successful.

What are your responsibilities? Please take us through your normal work day? 

As a coordinator of the Research Schools my main responsibility is to shape the Research School program within the framework set by the Research School Scientific Management Board. This includes recruitment, course development/selection and student support. 

I do not do this alone. I work together with the students in the program to see which courses work for them and with the group leaders in the community to develop and give courses, to run the selection procedure in the recruitment. On a daily basis, I work together with Astrid and Amelie in our office on all these aspects and to make sure that the Research School Program fits within the overall strategy of our epigenetics community.

How a normal workday would be, usually depends on the main project and the time of the year. As we had the interview symposium in the first week of March, January and February were devoted to the preparation of the symposium and the selection procedure of the applicants. Currently, I am working on the development of several courses and the TAC symposium course just started again. At the same time, I am working already on the outline of the next international call and the internal recruitment.

Other projects are course development/assessments, internal PhD recruitment, the yearly retreat and student events, such as the lecture journal club series.

My typical day starts with writing and checking emails, to make sure all different projects are moving along as they should. Then I continue to work on the project at hand. This can be writing further emails, making phone calls, preparing documents etc. I used to joke that as a PhD student, I would move small quantities of liquid from one tube to the next. Now I am writing emails and making phone calls.

This year our new research school ‘EpiCrossBorders’ has been launched. What is the difference to the program we had before? What do you personally like in EpiCrossBorders?

The main difference between EpiCrossBorders and the program we had before is the international character. We not only collaborate on an organizational level with Edinburgh, but all upcoming projects are collaborative as well. As a small explanation, the project in EpiCrossBorders are joint projects between labs at the HMGU and Edinburgh with an associated 6 month stay in the partner lab. This means that every PhD student, who enters the program right now, immediately builds an international career and network. 

For me as a coordinator, I really like this international aspect, which is really unique. It adds new challenges but the international character brings in a new refreshing culture and it should give new options to students from both the HMGU and Edinburgh. I am really looking forward to fully optimize the options that we have available now.

In contrast to the years before, this year’s symposium had to be virtual. How was the organization compared to the previous ones? What are the advantages and disadvantages of a virtual interview symposium?

Let start with the advantages: A virtual interview is much cheaper: no flights, hotel or catering bills etc. Also, the logistics are easier. No transport from the hotel and back or between Großhadern and Neuherberg had to be organized, no room bookings at the center had to be made etc. The software options we used – GoTo meeting for the presentations and Bluejeans for the interviews – were very suitable for an interview symposium. There were very few software issues during the symposium, such some connection issues with individual applicants and group leaders but nothing major. All in all it ran very smooth.

Another advantage is that a virtual interview symposium is much more flexible in timing, there is no need for the applicants to apply for visa so the time between the closing of the call and the symposium itself can be shortened. Finally, as we did not need any flights or other modes of transport it is also much better for the environment.

So far so good. However, there are downsides as well, which are true for all virtual events. Talking with someone in a virtual setting is not the same as talking face to face. This makes social events far less spontaneous. Other events we normally had like the group leader dinner and student dinner were not possible to organize due to the large time differences between the applicants. Moreover, the applicants did not have the chance to see the campus, or have a look in Munich. In addition, lab visits are not really possible. While it is possible to have the lab members talk with the applicants, the applicants are not really seeing the lab. And I found it much more exhausting than an in-person interview symposium. This was something I actually underestimated.

You have already organized three calls for PhD students as research school coordinator. Thus, you had to read many applicants. How do you sort the ‘wheat from the chaff’? In your opinion, what makes up a good application?

When we select our applications the first thing we see is the online application. Here we first check whether everything we asked for is there and whether the average grade fits the minimum requirement (equal or better than the German 2.5 grade). When the average grade meets this standard, we will look at the rest of the application. So, how good is the applicant and what is their motivation (what do they want and why). The quality can be asserted from grades, written project abstracts, relevant experiences, CV, reference letters etc. 

The motivation comes from the motivation letter and in some cases from the reference letters. A key part in the application is the motivation letter, if the applicant cannot convincingly write why one wants to come to our program or do a project, there is very little chance of acceptance regardless of the excellence in the rest of the application.

Over the last 3 years I have seen that many applicants have difficulties to write a good motivation letter. Often these letters are very generic, they could fit to most positions or programs and it seems like that the applicant did not spend the proper time on the application for our program.

Other times the motivation letter is like a CV. It mentions what the applicant did, what one’s skills are and why that makes them good candidates for the program or the specific project. These letters are often more aimed towards our program and it is clear that the applicant wrote the letter specifically for our program, but we then still do not know why the applicant wants to apply. What makes them apply to our program? This in my opinion is the key for a good motivation letter.

In the end grades are not everything, it is the total package of how you represent yourself in the application that triggers the selection committee to invite you or not. This however, also makes it very difficult to exactly pinpoint why someone was invited or why not. It is usually in the details and since our program is competitive, we often have to reject good applicants.

What would you like to achieve in future EpiCrossBorders calls? Where do you see points for improvement?

When looking back at the last 3 calls I see 2 main points for improvement and both have to do with outreach. Firstly, our outreach to African and Southern American countries is low and we need to improve this. Diversity is such a source of inspiration and creativity because different views and diverse cultural backgrounds allow all of us to enrich our experiences and to grow personally. Secondly, I want to greatly improve our outreach to applicants with a plant or computational background. Plant biology, for example, is crucial in epigenetics research related to environmental stress including climate change. Computational biology is very important in developing new methods to analyze the complex data generated in the field of epigenetics, new models to explain Epigenetic phenomena and to further advance AI-based approaches to tackle the first two points.

One final question for you Wouter. You have two kindergarten kids at home and the third one is on its way. How do you juggle between your job and being a dad?

Juggling a family and work is very interesting, and can be challenging at times. Especially this last year with COVID 19 was challenging.

We, my wife Anita and me, see the family life as a team effort. We both play an active role in the house hold and taking care of the kids. But as my contract as a Research School Coordinator is half time, it is mainly my role to pick up the kids from daycare, prepare dinner clean the house etc. Before the pandemic grocery shopping was also one of my tasks, but now we almost always use delivery services for groceries. This is a bit more expensive, but with all the lockdowns we cannot really go anywhere either, so it balances out.

When the daycare is closed and only operates under emergency care, we try to use it as little as possible. This means that during those times I usually combine home office with the kids at home. Anita is a full time Post Doc so she often has to go to lab to be able to continue the project. But when my job requires more time, for example during the Interview symposium or selection procedure, she often works a bit less to look after the kids, so I can focus on work more.

This division of the roles works really well for us. I actually consider it a bit funny that our role division is different than the gender stereo type here in Bavaria. This sometimes leads to funny situations. For example, many restaurants have the baby changing table only in the women’s bathroom. Some people will look at you very angry if you are in the wrong bathroom until they see the kid who needs to be changed…

Ario Sadafi (PhD Student; Marr Lab) talks about his PhD project, what he thinks about home office and his experience as supervisor during the virtual internship...

Ario Sadafi is a PhD student in Dr. Carsten Marr's Lab at the Institute for Computational Biology. He supervised the project "Classification of Percoll Gradients for Patient Diagnosis in Hereditary Hemolytic Anemias" of Lucìa María Moya Sans during the first virtual Summer Internship Program of epigenetics@HMGU. In an interview, he told us more about his PhD project, what he thinks about home office and his experience as supervisor during the virtual internship.

Hi Ario, thank you for your time. You are a PhD student in Dr. Carsten Marr’s group at the Institute for Computational Biology. Can you tell us a little bit about yourself and how you ended up at HMGU?

Hi, thanks for having me. I studied Computer engineering for my bachelor's and master’s degrees in Iran and Italy respectively. After graduation to continue towards a PhD, I joined a European consortium focusing on red blood cell production, function, and clearance in healthy humans and patients. Working for an industrial partner of the project, I had to find academic partners and after searching for potential institutes I was referred to ICB at HMGU. I got to know Carsten and since then joined the Marr Lab to do my PhD.

What are you working on for your PhD thesis? What motivated you to do your thesis on that topic and what was the biggest challenge in your project?

I work on methods for automatic analysis of hereditary hemolytic anemias. These are a group of genetic disorders that are inherited from the parents and affect the red blood cells' shape and functionality. I am working mostly with bright-field microscopy images or recently on images of Percoll gradients where different bands are formed by the cells having different densities in an experiment tube. I help the wet lab partners to design experiments and look into the samples, e.g. by looking at subtle changes in thousands of cells belonging to a patient. Of course, the methods we develop are general machine learning approaches and can be used for other problems too.

Like any other interdisciplinary PhD student, the biggest challenge for me was to speak the same language and properly communicate with the experimental lab to understand their research and requirements in order to have a good collaboration.

Your most important work tool is probably your PC (plus a server with enough memory). So, working from home should theoretically be more easy for you than for wet-lab researchers. How has the pandemic affected your PhD thesis?

That’s true, I think we are not affected much relatively. We used to do home office sometimes also before the pandemic and I was finding those home office days very productive as there was no distraction or time wasted for commuting. But working from home every day brings up some challenges too. Besides famous ones everyone knows nowadays, I feel that a lot of ideas, solutions to the problems, and such were coming up in short talks we had when bumping into each other at the ICB building. These days most of the meetings are planned beforehand and are somehow structured. I miss those short and helpful spontaneous chats we had.

During the past months, meetings were mostly virtual. What do you think about the virtual setting for the future after the pandemic?

It was a bit challenging at the beginning, but now I think attending virtual meetings is much easier for us compared to the physical meetings we were used to before the pandemic. I assume it would be very constructive to keep having virtual meetings besides the physical ones after the pandemic too for the better flexibility they allow us to have. Sometimes, meetings were canceled because one of the participants was out of the city or at home, but with us getting used to virtual meetings such problems will not be a hindrance.

You participated as supervisor in our first virtual Epigenetics@HMGU internship. Why did you decide to offer a project?

Well, Carsten suggested it. It seemed to be a very good opportunity to reach out to the talented applicants who are excited to work in an agile three-month internship. I think the enthusiasm and a relatively short period of work allowed us to have better week by week planning in comparison with a master thesis.

How was the collaboration with your intern? Were there any difficulties because of the virtual setting?

I had a very good and friendly relation with Lucia. I cannot think of any difficulty because of the virtual setting. Maybe sometimes it is a bit easier to explain things in person with pen and paper but explaining things virtually is probably another skill we are slowly gaining during the pandemic!

Are you happy how the project has developed? Would you participate again or recommend the virtual setting to your colleagues?

Yes, we actually managed to get our work published at an esteemed Machine Learning conference! In the end, we could do more than what was initially planned. I think I would participate again if I have a good project proposal. This virtual setting allows us to work with people anywhere in the world and I think is an exceptional opportunity for both sides to use.   

What would you do differently the next time? Do you have any advice for students that think about doing a virtual internship?

I can’t think of anything that I would do differently next time. For the students, I believe doing an internship is really worth the time they spend and would help them decide about their future career by working in a research group for a few months. 

Dr. Daphne Cabianca shares with us how it is to start a lab in the middle of the COVID-19 pandemic, her first days in Munich, and gives insights about how it is to be a Mum and a Scientist.

Since April 2020, Dr. Daphne Cabianca is a group leader at the Institute for Functional Epigenetics. Recently, she presented the research focus of her lab, how to grow their worms (Caenerohabditis Elegans), and some preliminary results in our December Epigenetics@HMGU Internal Seminar. Before Christmas, she was so kind to e-meet for an interview.

Daphne, you have been in Munich since April. That means that you arrived the middle of the first lockdown. How was that for you and your family? Was it hard to find a flat?

Actually, we arrived in March, a few days before the first lockdown. To be honest, it was not easy. We were lucky to have been assigned an apartment in the Helmholtz guesthouse, but we did not have the time to adapt and get used to the new environment before the lockdown came. Besides, my son was used to see other children in the daycare and it was difficult to explain all these major changes to him that was just 3 years old. 

For the flat, we changed our initial plans of searching with calm and decided to rent one that we saw just before the lockdown. We wanted to solve the issue of the flat quickly because we didn´t know until when we would have to postpone otherwise… So, we moved in the middle of the lockdown and entertained ourselves building furniture!

For your move, you probably had concrete plans how it should be and you probably had many expectations for your first days in Munich. How was the reality?

Well, the original idea was to take some time for ourselves before the adventure of the new jobs, relax a bit by exploring Munich and surroundings and have the time to do the adaptation in the kindergarten. Obviously, the reality was completely different as we entered in a lockdown after 1 week from our arrival. 

You have started your lab during the lockdown. Can you tell us how that was? How was your first week as group leader? What were the challenges?

It was weird… Probably the main challenge at the very beginning was trying to integrate in a new institute without the possibility to meet people in person. I was mainly participating to virtual meetings and arranging orders with my technician.. It was really weird to ask a question in a lab meeting without having the possibility to introduce yourself in person!

A lab is nothing without members. You have already a technician and a PhD student. You could not meet them in person, before you hired them. For you, did the virtual setting make it harder to take a decision? How were the virtual interviews?

For the technician, it was easier as we could meet in person in January of last year when I came to Munich. For the PhD student and for the postdoc (that will start this month!) it was difficult not to experience the in person “gut feeling”. However, I was very lucky to have the support of many members at IFE, including the other PIs, who participated to the virtual interviews of the “top” candidates and gave me feedback. This was extremely helpful to take my own decisions and I am very grateful for this support from IFE members.

You presented your lab during the last Epigenetics Internal Seminar and even though, the start was unusual, your group has many 2020 wins. Can you tell us what they are and why they are wins?

Well, I am glad that you think we have many wins… to be honest, I don´t know if I would have used this word because I feel that this adventure is still at the very beginning. However, surely, I am very happy that despite the pandemic, the lab was put together, we recruited people and started to do experiments! 

What are your wishes for 2021 for your group?

I wish that we continue the process of building the Cabianca team, not only in terms of number of people but, most importantly, also in terms of good communication and organization. And of course I wish that we have many many (can I say many again? ;)) nice results! 

You have a 4 year old son and you got him during your Postdoc at the FMI. A Postdoc is usually very demanding. Can you share some insights how it was to be pregnant and how it is to be a mum and being a scientist at the same time? What were the challenges and how did you manage them? Do you have any advice that you would like to share with us? 

Ah, I could write pages on this topic because I see it as a critical (positive!) turning point in my life, but I will try to be brief ;) 

I was very lucky with my pregnancy and I managed to work in the lab until the end. Then, I took the 18 weeks of maternity leave given by the FMI. Although tired, I was happy to go back to work after this time spent at home. It felt good to do something that I truly enjoyed and that was just “for myself” for some hours a day. 

Nonetheless, as time passed, things became gradually very tough because I didn´t have proper sleep for more than a year, as my son was frequently waking up at night. I faced difficult moments where I felt completely stalled with my project and also with my life, because I was beyond exhausted and I simply could not think as I used to. However, at one point, I pulled myself back together and searched for a concrete solution. I realized that I could ask for help to an expert in toddlers´ sleep, something which turned out to be crucial to find a solution that worked for my family. This gave a boost to my confidence levels. It increased my awareness that I could face adversities and find successful solutions! I started to believe much more in my capabilities and this had a very positive influence also in my attitude towards science and my career. Indeed, I believe that this was key to get me where I am now. Therefore, although challenging, being a mum has helped me a lot also professionally!

Becoming a parent is such a personal experience that it is hard to give advice as nothing fits everybody. However, for me it was important to accept that the working time schedule could not be the same, but that with a lot of organization you can still be efficient. It was also important to understand that I have limits. It can happen that some days I feel “better” at science and others as a mum, and accept that this is ok. 

In practical terms, it was very useful that my postdoc supervisor (Susan Gasser) arranged things so that I would get full support from a technician during my maternity leave and in the first months after I came back to the lab. So, if the organization in the lab allows it, I think that this is something that PIs should consider in order to support new mums (or dads).

The PhD student Jessica Pellegrino talks about her project at the IFE

 

 

 

Jessica Pellegrino is a PhD student in Robert Schneider’s team at the Institute of Functional Epigenetics. Here she tells us more about her research and what it’s like to work at Helmholtz Zentrum München.

Can you explain the question you are addressing and the main importance of your study?

Jessica: My research focuses on whether a cell, when challenged with a stimulus, can remember that it was challenged and thereby adapt its response when it is challenged again. Simply put, I take away glucose from a cell in culture and it has a response that can be measured by changes in gene expression. The cell is then allowed to recover by giving it back glucose and then we take away the glucose a second time. The cell shows a gene expression response that suggests it “remembers” this challenge and therefor can adapt to it. The main goal of my project it to study this “transcriptional memory” and to determine how it works.

What is the biggest challenge in your project?

Jessica: The most challenging aspect of my project was establishing the proper system to study this transcriptional memory. I spent many months optimizing the system and timing of the experiments. Though this was very painstaking work at the beginning, it paid off once I began my experiments and I was confident I was looking at the correct time points to answer my questions.
 
What attracted you to do your PhD in the Schneider lab and what is your favourite thing about the Helmholtz research environment?

Jessica: The choice to do my PhD in the Schneider lab was a combination of my interest in the study of epigenetics and the ability to work on an independent project but still receiving guidance from Dr. Schneider and my lab mates.

The Helmholtz research environment is very diverse in respect to both the research subjects and the people who work on them. I enjoy learning about the work done at Helmholtz, even if it is not directly related to the field I am in and that inspires me to think about science in different ways.

Visit the lab webpage to find out more about work in the Schneider team

Diego Rodriguez-Terrones - PhD student in the Torres-Padilla Lab - tells us more about cell potency

 

Diego Rodriguez-Terrones is a PhD student in the Torres-Padilla group at the Institute of Epigenetics and Stem Cells. He recently co-first authored a paper in Nature Genetics looking at the mechanisms behind changes in cell potency. Here he tells us more about the study and his research motivations.

In your recent publication you identified a mechanism through which embryonic stem cells in culture can change to cells resembling those found in the 2 cell embryo. Could you explain the importance of this transition and the main take home message of your study?

Diego: In the lab we aim to understand the molecular basis of totipotency, which is the capacity of a single cell to give rise to an entire organism. For example, in the mouse, the one cell of the 1-cell embryo and each of the two cells from the 2-cell embryo are the only three totipotent cells that occur during development. What this essentially means is that, if you let a 1-cell embryo develop to term, you will get one mouse, and if you split the 2 cells from the 2-cell embryo and let them develop independently, you will get two twin mice. This unique capacity of these three cells does not occur later in development and we are interested in understanding why. Unlike pluripotency — for which the field has accumulated an extensive understanding of its regulatory foundations and has even been able to induce pluripotent cells in vitro for over a decade — we have few insights into the regulation of totipotency and the molecular factors that confer totipotent cells their exceptional cellular potency.

A few years ago, another group reported the existence of a small subpopulation of mouse embryonic stem cells that recapitulates some features of totipotent cells, and because of their resemblance in some aspects to the cells of the 2-cell embryo, they were named 2-cell-like cells. In our recent publication, Xavier Gaume, a post-doc in our team, and I aimed to clarify the origin of this peculiar cell population and the molecular determinants that regulate their emergence. Using an ensemble of single-cell techniques, we managed to identify a set of intermediate cellular states that mouse embryonic stem cells undergo when transitioning to the 2-cell-like state. This information helped us to understand how the 2-cell-like population typically emerges in vitro, and permitted us to observe it live using time-lapse microscopy. Additionally, we also undertook a screening to identify regulators of the distinct steps of the transition and managed to identify several protein complexes that restrict entry into the 2-cell-like state.

What fascinates you most about the question you are addressing?

Diego: Well, I think it’s beautiful to discern the diversity of regulatory states that coexist in embryonic stem cell cultures. In our study we have identified at least three distinct populations based on their gene expression programs and then used this information to track the transitions between the different states. I really like that! It’s like having Waddington’s landscape  on a dish, and the ball sometimes kind of gets back to the top of the hill by itself!

What was the biggest challenge in your project?

Diego: The biggest challenge was probably the very rare nature of the 2-cell-like population, which prohibited us from employing many techniques that require high cell numbers. This actually turned out to be a strength, however, since it forced us to employ single cell techniques which permitted us to observe phenomena that would not be possible to discern otherwise.

What is your favourite thing about the research environment?
 
Diego: It’s certainly the confluence of so many teams working on epigenetics and stem cells in a single community. You can certainly count on someone working with the technique or the aspect that you have in mind, and who you can consult if needed. It’s also really good that there are also many, many seminars happening all the time, perhaps even more than you have time to attend to!

More on Diego's publication: Rodriguez-Terrones, Gaume et al., (2018) Nature Genetics and Helmholtz Zentrum Press Release

The PhD student Lea Schuh from the IFE and ICB shares her experience about her time abroad

Lea, thanks for taking the time to talk to us.  You are currently taking part in a research project as part of the International Partnership with UPenn Epigenetics Institute. Could you tell us a bit about the project you are working on and what motivated you to participate in the programme?

Lea: Thank you for giving me the opportunity to share my experiences! I joined an ongoing project where we are trying to understand the origins of resistance in melanoma, a common form of cancer. Only around 1:1000 cells may acquire resistance – but these suffice to provoke relapse in almost 80% of the patients. 
The Raj lab at the University of Pennsylvania has so far been able to propose a two-step mechanism leading to stable resistance: 1) before drug application, cells may reversibly transition from a non-resistant to a transient-resistant state 2) after drug application, only cells previously in the transient-resistant state may survive and are then subjected to epigenetic reprogramming completing the transformation to stable resistance. 
By computational simulations, I am trying to identify the role of stochasticity within a particular gene network and its influence on the formation of rare-cell behavior. Specifically, I am trying to understand what kind of network architectures and network properties are essential to elicit rare-cell behaviors. We hope that this might lead to a better understanding of how transient-resistant cells are formed in the first place.  

Personally, participating in this exchange has been about broadening my horizon – educationally as well as personally – and getting out of my comfort zone. This opportunity enables me to gain experience in an exceptional lab which elegantly combines cutting-edge computational and experimental biology, to work with a group of excellent researchers from very diverse educational backgrounds and origins, and to explore a new country with its language, culture, and people. 

What fascinates you most about your project?

Lea: So far, this project has revealed the general mechanisms leading to resistance formation in melanoma – simultaneously, it has triggered a whole set of new questions about the more detailed biological and genetic events underlying, controlling and driving these mechanisms. What fascinates me is the scope of these questions and the diverse research areas addressed by them. It highlights and promotes the necessity of interdisciplinary research and allows for a wide range of experimental and theoretical approaches.
 
What is your favourite thing about the research environment?

Lea: Honestly: curiosity! The research environment promotes curiosity, open-mindedness and innovation in terms to pursue the former. It allows for and grows with unforeseen developments and pushes each and every single person to keep on questioning and coming up with new and exciting hypotheses. 

What do you like to do in your spare time?

Lea: I love to go running which also is a great way of exploring Philadelphia – the pedestrian-friendliest city in the US! Apart from that I enjoy visiting museums, reading and travelling. I am really excited to go to Washington DC, New York City, Chicago and Boston during my stay here.

Nilay Shah talks about what he learnt during his PhD studies

Nilay Shah recently completed his PhD in Dirk Eick's lab.  Here he explains his recent publication in Molecular Cell, looking at the role of RNA Polymerase II in transcription termination, and some things he learnt during his PhD studies.

In your recent publication you discovered the role of RNA polymerase II in the regulation of transcription termination.  What makes this research so important and what was the biggest surprise for you during this study?

Nilay: In our study we described how the C-terminal domain (CTD) of RNA Pol II contributes in the tight regulation of termination processes for sense and antisense transcripts. This work is very important, as it will pave the way to better understand and decipher the detailed mechanism of Pol II termination, a process that still remains poorly understood.

The biggest surprise for me was the extent of the termination defect phenotype that we observed in our Pol II mutant. The effect was massive spanning up to several hundred kbs.
 
What keeps you motivated working in the lab?

Nilay: It is a lot easier to remain motivated when things are working well during the project. However, it gets difficult when things do not work according to the plan. 
I am fortunate enough to have a bunch of fantastic people around me, including my colleagues and friends who helped me remain motivated. 
 
You recently finished your PhD, what’s the most important thing that you learnt during your PhD?

Nilay: The most important thing I learnt from my PhD was the art of perseverance. At times, it was important to remain patient and keep working hard. 

More on Nilay's publication: Shah, Maqbool et al., (2018) Molecular Cell and Helmholtz Zentrum Press Release

Alex Wolf talks about his research and why it fascinates him

Dr. Alex Wolf is a postdoctoral fellow in the Theis Lab of the Institute of Computational Biology.

In your recent publication you developed a computational approach for the analysis of single cell gene expression data. What makes this research so important?

Alex: By reporting distributions over single cells, single-cell data provides a whole different level of insight compared to bulk data, which only report tissue averages. We all know that the average income of a country doesn't tell us much about the well-being of its citizens: a decently appearing average could hide the fact that there are a lot of poor people with a single billionaire. Similarly, many diseases are extremely heterogeneous in terms of their cellular composition. By contrast, different individual humans become more similar at the single-cell level, when ignoring the cellular composition. That is, many differences between humans are due to their different cellular compositions. This is also why a project like the Human Cell Atlas makes sense: the cells of very few individuals can serve as a generic reference for the basic building blocks of life for all humans.

Scanpy is a toolbox providing the canonical data analysis methods for gene expression data at the scale of millions of cells. Hence, it is able to deal with the amount of data generated in the Human Cell Atlas and can be used for jointly analyzing - aggregating - published studies.

What is the biggest challenge in your work?

Alex: Understanding fundamental questions that biologists ask and finding efficient ways for writing tools that helps answering these: the challenge is to balance the strive for beautiful concepts and code with "making things work" and the need of addressing biological details. Being good at guessing what can be computed and what cannot.

What motivates you to pursue this particular research line?

Alex: It is a highly dynamic, lively research field with potentially a lot of applied and fundamental impact.