Monday, 29 March 2021 09:14

Interview UFR

Written by
Early Stage Researcher, Rubí Misol-Ha Velasco Cárdenas MSc.
  • What are your research interests? What are you working on?
Cancer Immunotherapy, Biotechnology. I am attempting to improve the CAR T cell therapy introducing intracellular modifications in the design of them. I perform in vitro and in vivo assays of the new constructs and compare them with the current FDA approved CAR Kymriah.
  • How did you decide to make this the focus of your research?

I always had a wide interest in immunology and the relation with this science and cancer caught my attention for the high potential that I find in immunotherapy against cancer.

  • What would you like the impact of this project to be?
A better understanding of the CAR T cells and hopefully a new therapy that can be used in the clinics.
  • Where and how did your scientific journey begin?
It started when I was a child and I got my first set of chemistry and a microscope, I could not stop doing experiments and trying to observe everything under the microscope.
  • What do you plan to do after you complete your PhD?
Continue doing science as a postdoctoral researcher.
  • How has your view of Science changed with this consortium?

It made me understand the relevance of networking and teamwork, especially international collaborations. It also helped me to be more open to different styles of work and of making science.

ITN

  • Was there something specific about the ENACTI2NG that drew you to apply?
The collaboration and the topic, as well as the opportunity of moving to a new country where I never lived before and learnt from them.
  • Optional: How do you think the ENACTI2NG consortium is contributing to put you one step closer to your goal?
It is helping me in the transition from an early-stage researcher to a more advanced or mature researcher, more independent, which a higher expertise in cancer immunotherapy.
  • Someone curious about participating in a consortium like asks for your feedback or advice, what would you tell him/her?
I would tell him that being in a Marie Curie Sklowdowksa Consortium is one of the best ways of studying a PhD and that I highly recommend it.
  • Someone is curious about working on the same field / working with your group, what would you tell him/her?
That this field has a high potential for the future, not just as a “hot topic” but for the actual impact that might have for the treatment of cancer and improving the quality of life of these people.
  • What do you like most about your time at your institution/group/consortium?
I like the collaboration, that everyone is open to bring ideas to the table but also to listen and learn from the others. Everyone has a different expertise, and this make us be a complete consortium.
  • How is the process of adaptation into a new country during the PhD?
Indeed, is a very difficult process that takes time and patience (like science), but that make you become a more resilient, determined, humble and knowledgeable person and researcher.

PI: Susana Minguet

  • What is the focus of your group?

We are interested in understand how our immune system work to keep us healthy. In particularly, we study lymphocytes that are the cells that distinguish self from non-self and establish the immunological memory. We aim to understand how these cells transmit the information of self or non-self across the cellular membrane and how they decide when to mount an immune response.

  • Where and how did your scientific journey begin?

In high school, I had a teacher that told us about the immune system and about the “bubble boy” disease, kids that are born without a functional immune system and they should live isolated from the world. Any minor infection might kill them. This story made me realized how important our immune system is, and I wanted to understand this better. Then I decided to study Biochemistry and Molecular Biology and did my PhD in Immunology.

  • The favorite moment of your career.

It was during my postdoc in Germany, one of this Eureka moments when you do the key experiment and it works! I was sitting in front of the flow cytometer and observing the calcium response of my cells live. I had two kinds of stimuli that did not activate the cells, and then I had the idea that maybe both stimuli were needed simultaneously. And I add then, and the cells responded beautifully! I was so happy, I phoned my supervisor and we start celebrating by phone, it was great!

  • One thing in science that changed the most since your PhD (early science career) - something that would have made you life so much easier if you had it back then?

Soft skill courses, presentation courses, English writing… at that time there were not graduate schools and nobody took care of teaching us all of this. I also missed some kind of thesis committee or someone that helped us to put our PhD progress in perspective.

  • Developments you are most excited about.

Science communication in general, Immunotherapy and vaccines for COVID19

  • What will be the next big thing in the field?
Personalized medicine, off the shelf immunotherapies

PI Wolfgang Schamel:

  • What is the focus of your group?

Molecular mechanism of T cell activation

  • Where and how did your scientific journey begin?
In Bochum finding, catching and bringing small animals at home, when I was a child.
  • The favorite moment of your career.
Discussing exciting new data with my co-workers.
  • One thing in science that changed the most since your PhD (early science career) - something that would have made you life so much easier if you had it back then? 
DNA sequencing by just putting the sample into the post
  • Developments you are most excited about.
Immunocancer therapy
  • What will be the next big thing in the field?
Allogeneic CAR therapy
  • Day to day life of a PI (and how much the consortium demands out of you).
Zoom meetings
  • A PI curious about submitting an ITN asks you for feedback or advice on it, what would you tell him/her?
Please go ahead!!
  • What do you like most about the consortium?
Following the project of others
  • What do you envision the future of science to be? 
Free exchange of information
Monday, 01 March 2021 09:37

Interview TUW

Written by

Early Stage Researcher Lukas Velas, MSc

  • What are your research interests? What are you working on?

I am studying spatial distribution and mobility of the proteins within immune synapse by means of fluorescence microscopy. In my PhD I have implemented a 3D superresolution fluorescence microscopy setup that allows us to localize single proteins with precision of 10 nm in all three dimensions and applied it to study the distribution of T cell receptor upon different conditions.

  • How did you decide to make this the focus of your research?

During my physics studies I was fascinated by the technology that allows us to see single molecules by tagging them with a fluorophore. I wanted to get closer to the development of these methods and their applications. Furthermore, immunology is an exciting field in which many fundamental questions remain unanswered. Hence, I really liked the idea of exploring the world of T cells with superresolution microscopy.

  • What would you like the impact of this project to be?

I would like to bring new insights into arrangement of T cell receptor and other proteins in the immune synapse before and after T cell activation.

  • Where and how did your scientific journey begin?

I started with studying Physics at Charles University in Prague. During my studies I got attracted by problems in biology which could be addressed by biophysical methods. I worked in a couple of biophysics laboratories at Charles University as well as Czech Academy of Sciences. There I for the first time contributed to real research and attended conferences. Here I realized I wanted to pursue this journey with applying for a PhD position.

  • What do you plan to do after you complete your PhD?

I am remaining open minded. I would like to gain further results from the techniques and knowledge I have gained during my PhD. But I think I would also be happy in R&D departments of some company. The most important for me is to be in touch with modern technology and its application to important problems.

  • How has your view of Science changed with this consortium?

Thanks to this consortium I was able to see top science. Either by working in a top end laboratory, collaborating with great partners and attending big conferences and meetings.

  • Was there something specific about the ENACTI2NG that drew you to apply?

I was attracted by the quality of partners involved in the consortium and the proposed extent of collaborations. Furthermore, the possibilities in the lab of prof. Schütz were exactly what I wanted to explore. Also good and stable funding of the project for 3 years was a big plus.

  • How do you think the ENACTI2NG consortium is contributing to put you one step closer to your goal?

It allows me to pursue my scientific questions in a great environment of colleagues, collaborators and with all the necessary equipment.

  • Someone curious about participating in a consortium like asks for your feedback or advice, what would you tell him/her?

I would say it’s a great opportunity for everyone who wants to pursue science and I would encourage everyone to apply. However one must keep an eye on the duration of the project since for some scientific questions 3 years might be too tight.

  • What do you like most about your time at your institution/group/consortium?

(institution) I like that its modern, its based in the centre of Vienna and provides me with everything I need.

(group) I like the friendly and helpful atmosphere in the group. Also the availability of my PI to discuss my research.

(consortium) I love our meetings, the PIs are very friendly and supportive and the students are a great fun.

  • Would you apply again?

Definitely.

Monday, 01 March 2021 09:36

Interview UWÜ

Written by

Early Stage Researcher Vasco Gonçalves, MSc

What are your research interests?

My research interests… Oh that’s tough, that’s almost a spiritual question. Should I talk about what sparks my interest and curiosity or what I am actively researching in the lab?

It’s an open end question, you’re free to address it how you see fit.

Thank you for narrowing that down [laughing]. My research interests… Ok, let’s focus on the ones that have had the most influence on my research orientation so far. One is immunology obviously, the way that our bodies are able to defend themselves; and the other is protein engineering.

And I think that both merge very well because on one side we have this knowledge oriented tool creating solutions for biological problems and on the other we have this amazing blueprint of an already accomplished system. In a sense immunology is the book that we are reading to inform our protein design choices. And Chimeric Antigen Receptors (CARs) are perfect examples of this marriage. Someone though “wait a second, this can be better if we do it like that” and for me this is the perfect definition of rational design, or intelligent design. It creates this interesting nuance to cancer immunotherapy, where we’re not only fighting malignancies by modulating our own immune system, but we are taking lessons from it and generating improved versions of proteins or repurposing them to further boost it.

And the interesting thing about CARs is that although they mimic the natural T cell receptor and other immune co-receptors, they are not necessarily the same. Meaning, they have in their own set of rules, obviously these rules are based on natural ones but they still need to be defined and understood. And this is where my project and my hypothesis come into play. We are questioning if CARs can be improved regarding certain aspects like antigen sensitivity and signal transduction, we look into why certain interactions are happening more or less than anticipated and if we can manipulate them by changing the design of this synthetic molecule.

I think this is very exciting, there is this design and creativity side to CAR-T cell research that, can be very rewarding.

And what sparks your interest outside of your main topics?

So many things. I like systems biology for example. Because again, we are talking about something that requires some form of creativity. You need to be creative to work with big data and in the end to visualize something out of it. I also love to read about virology and epidemiology and on the other end of the spectrum I like social sciences, anthropology, psychology. But this are things that come out of curiosity and it is not really something that I actively contribute to.

How did you decide to make Cancer immunotherapy and in particular CARs as the focus of your research?

I have always been drawn by the transnationality of research, especially in health. This idea that you are doing something that can be utilized in society in the next couple of years if very fulfilling. It feeds this sense of accomplishment in being able to contribute with something that is tangible. 

And right now, being involved with cancer therapies happened because suddenly I had this amazing opportunity to be part of something bigger, of being integrated in a network of people striding for excellency and knowledge… And of course you take this opportunity. To be honest, I wouldn’t trade it for anything else.

And in a developmental sense it feels like and organic step for me. I have started with antibody development back in the day and moved my way into living drugs, into cell products combined with recombinant proteins.

Where and how did your scientific journey begin?

Listen, my mom tells me that I was already counting ants and mixing leftover drinks at dinner parties doing “experiments” way before I went to school [laughing]. But officially my first time in a lab, working on my own project, was during my masters. 

I had this plan in my mind that I wanted to work with HIV and  biopharmaceutical development and in the faculty of pharmacy in Lisbon there was this small lab doing exactly that. So again an example of a plan that worked out in the end. I had a very interesting time there, I learned a lot about antibody development and it was actually my first time hearing about CARs. I think that this idea of a repurposed T-cell with all of this potential was very enticing to me, and speed forward a few years later, here I am, working with CAR-T cells.

What do you plan to do after you complete your PhD?

Well, first thing I plan to do is to take a deep breath and appreciate the fact that I have made it. I am a first generation graduate student so finishing a PhD will be this… it is the end of an academic cycle isn’t it? I mean, you can keep going on in academia, but this is the big moment where you officially stop calling yourself a student. No longer will you have those student discount benefits [laughing]. But it is going to be a big moment for me, after a bachelor and a masters, I feel like I need to take a moment and be proud of what I have accomplished and appreciate my parents for standing by me throughout this journey also.

Professional speaking, I am keeping an open mind about it. I have been in academia for a while now and I have peeked behind the curtains, but industry is still something that sparks my interest. I have had the opportunity to work closely with some pharma companies but always from the academic perspective, so I still wonder what’s on the other side, what it is like to be in industry… I should start focusing on my next 5 year plan right? [laughing]

So industry might be the next step?

It is a possibility yes. But again, I am quite open to try new things. A post doc position might be the thing that I am more familiar with, so it would be a smoother transition, but I also would like to challenge myself further and broaden up a little. See what else I can do.

For example, I have also become quite interested in science communication. Specially working with Scienseed (our collaborator) for these past couple of years, and that has made quite an impression on me. I like the different aspects of design and almost marketing that it brings to science and its dissemination.  

About ENACTI2NG, was there something specific that drew you to apply?

Yes, a couple of things. So besides the topic, which is very important, I was drawn by the idea of scientific and personal growth. ENACTI2NG is a training network so the focus is your development as scientists obviously but, it’s not only the technical skills that take center stage, you’re also groomed to be a fully realized professional. You have access to this established network of amazing scientist, that you can easily take advantage off, and that are, at the same time, invested in both the science that you’re making and in your own personal development. I think those are some of the strongest points of being part of a network like ENACTI2NG.

Someone curious about participating in a consortium like asks for your feedback or advice, what would you tell him/her?

Go for it! Definitely! I think it is quite fulfilling and the amount of meaningful connections that you make while collaborating so closely with interesting and interested people is quite empowering. It’s both about you and it’s about science. Again, I do consider myself lucky to be part of ENACTI2NG and if someone would ask me if they should join a consortium like this, that is invested in their program and in their early stage researchers, I would definitely support them. I was lucky myself to have someone believing in me and pushing me to apply, and now I am in this position where I can be proud of being a part of the ENACTI2NG family.

Friday, 05 February 2021 12:15

Interview CSIC

Written by
Early Stage Researcher, Ivaylo Balabanov MSc
  • What are your research interests? What are you working on?

I have broad research interests. From basic immunology through cancer immunotherapy to neurobiology and endocrinology. I’m currently working in basic or basic-to-applied immunology – trying to understand more about the T-cell receptor and its functional characteristics, so I could apply the knowledge in the design of chimeric antigen receptors (CARs) against different blood cancers, in particular Acute myeloid leukemia.

  • How did you decide to make this the focus of your research?

The topic of my project fit quite well with my research interests. It’s about immunology and cancer biology and it’s about designing novel therapies – particularly attractive subject for me. I’ve always been drawn by career opportunities with social impact and I find this the perfect research area for me. My goal with this project is to contribute with one small step in improving CAR-T-cell therapies, so they find their way into the clinic soon and start saving patients. The prospect of me contributing to science and society in this way would be the ultimate feeling of fulfillment and success.

  • Where and how did your scientific journey begin?

My scientific journey started as a Bachelor student in my home country Bulgaria in a lab of experimental immunology, where together with fellow undergrads I learned the basics about the immune system, about cancer and autoimmunity. I was introduced to many methods and techniques; taught to handle laboratory animals, but most importantly how to design and execute experiments – all skills I have since needed and further improved. During the three years I spent there as a trainee in a young and motivating environment I developed a strong bond for immunological research and decided to dedicate my career to it.

  • What do you plan to do after you complete your PhD?

My view for the future has not changed much since before I started my Ph.D. I still like what I do and therefore I plan to stay in academic research – do a postdoc or two, depending on opportunities, but also on private life changes. I believe being a part of the ENACTI2NG consortium, thus accumulating skills and contacts puts me in a good position for the future.

  • Was there something specific about the ENACTI2NG that drew you to apply?

What drew my attention to the ENACTI2NG project was first the topic – of particular relevance and one which matched my interests completely. Second, but equally important, was the international composition of the consortium, the various expertise of the participating groups with which a common topic was being investigated. When I found about ENACTI2NG I was completing my Master’s degree in Japan and had planned not to apply for positions yet. However, even though I had no idea at the time of the scientific prestige of MSCA networks, I immediately recognized this was a unique opportunity for me. Being part of ENACTI2NG allowed me to meet great researchers – both on the PI and the ESR side – the interactions with whom have enriched me enormously and further raised my ambitions for the future.

  • Someone curious about participating in a consortium like asks for your feedback or advice, what would you tell him/her?

I’d definitely encourage anyone considering of such network project to apply. Being part of a consortium gives numerous options for exchange, training and collaboration, and thus multiple career opportunities. Science is team work, so the more contacts one builds early on, the better for their future

  • What do you like most about your time at your institution/group/consortium?

I like the group I’m part of at my institution a lot. It’s a great team environment. I’ve learned a lot for the three years I’ve been here and I’ve also culturally enriched the group with my diverse background. I love the fact I’m able to build my own work schedule and deliver to the best of my abilities.

PI: Hisse M. van Santen

  • What is the focus of your group?

We mostly work on the T cell Receptor (TCR), a protein complex expressed by so-called T cells that allows these cells to recognize pathogens such as viruses and bacteria and mount an immune response to these pathogens. T cells are critical components of the immune response that can protect the body from pathogens but also cause damage when generating a response against its own organs. T cells have to learn to discriminate between pathogens and its own organs and this learning process is dependent on how the TCR transmits signals to the T cell during the development and function of the T cell. We study these mechanisms using mice with genetic changes in various components of the TCR and study the development and function of the T cells in these mice, both when encountering a pathogen or upon inducing an autoimmune response against its own organs. This type of studies allows us to identify critical components of the TCR and understand the underlying molecular events that lead to these responses. Such knowledge is necessary to develop therapeutic strategies that improve immune responses against pathogens or inhibit autoimmune responses.

The EN_ACTI2NG network has stimulated a new line of research in which we try to optimize recombinant receptors ('Chimeric Antigen Receptors' or CARs) that make T cells better at recognizing and eliminating tumor cells. We focus here on the part of these receptors that transmits signals to the T cell upon recognition of the tumor cells, using our knowledge obtained from our fundamental research on the TCR to make new variants of these CARs.

  • Where and how did your scientific journey begin?

My interest in biology was stimulated by a very inspiring high school teacher who taught us the basis of genetics and biochemistry without books and with just fantastic blackboard schemes. Best thing was that he only needed 30 minutes of each class to teach the subject matter and then told all sort of stories about his dogs and the neighbors or showed us organs and body parts from cows and pigs obtained via a veterinary connection at the local abattoir.

  • What would you like the impact of your career to be?

Provide reliable and solid data and ideas about basic T cell biology and, hopefully, finding ways to make better CARs that could be used in the clinic. Also, providing early career scientists with the tools and knowledge to launch their own scientific career.

  • The favorite moment of your career.
Helping to set up and starting the new laboratory of my PhD supervisor Hidde Ploegh at MIT. The experience of living in a new country, the number of great research groups at close distance, fantastic seminars almost every day and ample resources to do science were simply overwhelming.

  • One thing in science that changed the most since your PhD (early science career) - something that would have made your life so much easier if you had it back then?

Fully annotated genomes, seamless cloning, CRISPR/Cas9, incredibly cheap gene synthesis (technically four things, but all related with facilitating molecular biology).

  • What will be the next big thing in the field?

Predicting TCR specificity from its amino-acid sequence (will be a hard nut to crack).

  • Day to day life of a PI (and how much the consortium demands out of you).

Paperwork, discussion with the students, seminars and meetings, writing grants and papers, evaluating manuscripts and projects, reading and thinking. I am the coordinator of EN-ACTI2NG but thanks to the help of fantastic project managers the demands have been bearable.

  • A PI curious about submitting an ITN asks you for feedback or advice on it, what would you tell him/her?

The most important is getting together a group of participants (in our case research groups, clinical groups, companies) that each can make a credible contribution towards a joint goal.

  • What do you like most about the consortium?

The enthusiasm of all the participants, the great opportunities to exchange information and reagents, being part of a group of excellent students and scientists.

  • What do you envision the future of science to be?

Curiosity-driven, conscious of moral implications of our work, able to inform and listen to non-scientists.

Friday, 14 August 2020 10:33

Interview STRATEC CONS

Written by
Early stage researcher Christoph Trenzinger, MSc
  • What are your research interests? What are you working on?
I am interested in the development of microfluidic devices that open new ways for biological research and point-of-care diagnostics. Currently, I am working on a microdevice for controlled confinement of T-cells. My aim is to study and quantify the effect of mechanical stimulation on the activation behavior of T-cells in vitro.
  • What would you like the impact of this project to be?
My results may contribute in the development of novel cell culture systems that use mechanical stimulation for T-cell expansion. Further, my project may also have impact on the development of Immune-Organ-on-a-Chip devices that replace animal testing for disease modelling or drug screenings.
  • Where and how did your scientific journey begin?

I would say that it really began when I was working as a student assistant during my master studies. It was the first time I got hands-on experience in the production of lab-on-a-chip devices. I was fascinated by this technology and its applications and from there on I decided to work on miniaturized systems myself.

  • What do you plan to do after you complete your PhD?

I want to keep developing microfluidic systems in an industrial environment.

  • Was there something specific about the ENACTI2NG that drew you to apply?

The chance of doing a PhD in industry was one reason for me to apply. I wanted to take the chance and develop my employability in an industrial environment while also doing research as a PhD. A second reason was of course the Marie Curie fellowship that offers opportunities to develop additional skills in several workshops and offers great supplies for doing research. The third reason was the overall subject addressed by EN-ACTI2NG, that allowed me to gain a better understanding in immunology and to collaborate with researchers working in this field.

  • Someone is curious about working on the same field / working with your group, what would you tell him/her?

Working in the field of microfluidics, means to work very interdisciplinary. A microfluidic device is only as good as its applicability. Next to the science behind microdevice production you do also need to have knowledge in i.e. biology and microscopy to be able to communicate with potential end-users.

  • What do you like most about your time at your institution/group/consortium?

The possibility of networking with people from various fields of research, may it be in the consortium or the company.

  • What can you expect from a PhD in industry?

I think it really depends on how well your’ and the company’s expectations match. So, I strongly recommend checking that before starting a position like that. For sure your PhD in industry will be different in terms of supervision and publications may not be the main goal during your time in the project. However, you will have the chance to develop skills that help you to find your place in an industrial environment and may kick-start your career in industry. Eventually you will also have a PhD degree and you can decide where to go next.

PI: Marco Linder, PhD 

  • What is the focus of your group?

Our company is focusing on the development and mass manufacturing of microfluidic consumables.

  • What would you like the impact of your career to be?

I want to continue to help develop products that are used in diagnostics and therapy. This motivation led me to join the company and also ensures that I stay in this field.

  • Any serendipitous findings during your career?

Yes, quite often. You have a piece of the puzzle, you can't do anything with it and you leave it there for now. After further experiments this puzzle piece comes to mind and the overall picture suddenly makes sense. In retrospective, this piece of the puzzle looks like a serendipitous finding.

  • One thing in science that changed the most since your PhD (early science career) - something that would have made you life so much easier if you had it back then?

My PhD was not long ago. But it's incredible to me how the internet has changed the past 20 years, how easy it is to communicate and to acquire knowledge. Unfortunately, many publications, although financed from public funds, are hidden behind a paywall. But I'm curious to see in what direction this will develop.

  • Developments you are most excited about.

Clearly learning algorithms. They include the ability to evaluate complex correlations (which subconsciously distinguishes experts from beginners), but will also make us have to question things anew.

  • What will be the next big thing in the field?

Microfluidics will benefit massively from learning algorithms and thus allow big leaps in molecular diagnostics; early detection and personalized treatments will be improved. Personally, I would like to contribute more on the device side, more on the basic idea than in the pure production.

  • Day to day life of a PI (and how much the consortium demands out of you).

The EN-ACTI2NG project managers (Hisse, Estefanía, and now Sofia) do a fantastic job and the ESR works very independently.

  • A PI curious about submitting an ITN asks you for feedback or advice on it, what would you tell him/her?

Beneficiaries are essential for the success of a proposal for an ITN, but a company should only participate if they are interested in the student's work. It is also helpful if the university that is additionally required for a PhD is not far away. This helps the discourse between academy and company and makes it easier for the ESR to attend its courses.

  • What do you like most about the consortium?

It is a good mix of expertise that is all about CAR and T-cells. Personally, I am impressed by how straightforward and friendly the communication between the experts is.

  • What do you envision the future of science to be? (or: what would you like it to be – comment on organization/economic level, equality or mental health focus)

I would hope that we do not lose sight of the value of basic research and its free publication. At the same time, research always has a responsibility that cannot be transferred to companies, regardless of who pays for the research.

 

Wednesday, 14 December 2016 18:33

Outreach

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Under construction

Wednesday, 14 December 2016 18:33

Outreach

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Under construction

Wednesday, 14 December 2016 18:33

Interview STRATEC CONS

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Wednesday, 14 December 2016 18:32

Blog

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November, 06 2018 - Seeing the invisible
November, 05 2018 - The science of reading in science: A never-ending story
October, 16 2018 - To kill or not to kill
May, 15 2018 - Armoring the body against cancer

 

November, 06 2018

Seeing the invisible

We all live in a rather small world. Our planet is around 12,000 kilometers in diameter, which may seem big, but we are orbiting our Sun with an average distance of 149 million kilometers. The Sun is one of approximately 300 billion stars that make up our galaxy and astronomers estimate that there are 120 billion galaxies just in our observable universe. What lies behind this border is and probably will stay a mystery. Truly, on a cosmic scale we can consider ourselves as a grain of sand in a vast desert.

Of course, this is how we see it from our perspective. If we appeared in the body of an ant, we would see humans as giants and indeed the world around us would feel much different. And we can go smaller than an ant! Thanks to our eyesight we are able to see details as small as 0,1 mm. And mother nature is by far not limited by this.

Leeuwenhoek MicroscopeThe “cosmos of small things” was observed for the first time by a Dutch textile seller, Antoni van Leeuwenhoek. He was using magnifying lenses to check the quality of linen. Luckily, linen was not the only thing he looked at. With further improvement of lens quality and magnification he discovered microorganisms, blood cells, muscle fibers, sperm and many other microscopic structures. He invented the microscope, and with it, he made a completely new universe – a very near one – reachable for us.

Since then, thanks to research and technology, microscopes might seem to change drastically compared to what Mr. Leeuwenhoek was using. The principle, though, stays the same. We use a set of lenses to magnify the sample, and instead of looking with our own eyes, we use very sensitive cameras. Microscopy led to significant discoveries in modern biology. It not only allowed to observe subcellular structures, but also processes like cell division. However, this type of microscopes, called “light microscopes” also have their limits. These limits are set by the properties of light and therefore we cannot see details smaller than 250 nm.

250px FluorescentCellsSo how can we solve this problem? A possible solution lies in what we know as fluorescence microscopy: a special type of light microscopy where we can tag the structures or even molecules that we want to observe with a “light” label. Then we activate the labels with a laser and record their positions. In this way we can study the movement, organization or even interaction of such labeled structures.

This is exactly what we do in the lab of prof. Gerhard Schuetz at Vienna University of Technology, where we address the questions of molecular biology with fluorescence microscopy. Concretely, in my project I use fluorescence microscopy to understand the behavior of proteins which our immune cells use for accurate recognition of harmful intruders in our body. We call these immune cells T-cells, as they mature in the thymus, and the special proteins we call T-cell receptors. How exactly T-cells work is a subject of continuous research; and we are still missing the full understanding. If the T-cells fail to respond appropriately, it leads to either inefficient healing or, on the contrary, allergies. Just as van Leeuwenhoek fought the problem of seeing very small organisms, we fight the problem of looking at what exactly the small T-cell receptors do. We believe that by using novel techniques that allow us to observe molecules in 3D space with a precision of 50 nm we will be able to contribute to the current understanding of immunology. We can see what Leeuwenhoek could ever dream of, and we could even wonder how he would feel knowing what we know now.

 

MSc. Lukáš Veľas
Institute of Applied Physics
Vienna University of Technology

Member of the ENACTI2NG consortium

velas (at)iap.tuwien.ac.at

2nd image from Wikipedia, the free encyclopedia

 

November, 05 2018

The science of reading in science: A never-ending story

From Martel’s bioluminescent pools to Dante’s infernal hellscapes - books introduce me to the wonders of the world around me, and to those within my mind(s). From fire extinguisher labels (PASS!) to the Mahabharata’s godly discourse alike, reading is not merely a bedtime ritual for me, but a compulsive, relentless habit; a therapeutic necessity that helps me bridge the elusive gap between what I know, and what I am yet to learn. It’s an itch that I always scratch.

Starting a PhD gave me the perfect opportunity to cement my status as a bona fide bookworm. An afternoon well spent involves chasing down protocols, jumping from paper to paper, reading page after page, till my eyes tire, till my tummy rumbles - not stopping until my curiosity is satiated. Schreiber, Stagg and Allison adorn my lab bench and nightstand; my imagination and dreams.

And yet, I feel like I have not “read a book” in the last couple of months.

I’ve read a lot – but not novels or anthologies of poems. Instead, I’ve exclusively read myriads of papers and scientific articles in immunology, cancer biology and biochemistry. Don’t get me wrong, I’ve enjoyed every minute of it, and the scholastic accomplishment I’ve gained is unparalleled. Yet somehow, in my mind, I feel like I haven’t “read”.

So, why do I feel this way?

Papers and novels both equally enthrall me; however, science reports discoveries, but fails to narrate them to me. The unique identity and beauty of the stories scientists yearn to recite is masked and standardized by white sheets of A4 paper and rigid writing formats of science. A ten-page paper never allows me enough time or agency to invest in its story, to immerse myself into the narrative and let my thoughts marinate and linger. I feel like I have not “read” because scientific writing formats do not allow me to internalize what the paper posits the same way I would relinquish myself over to the story of The Boy Who Lived. The moment I meticulously dissect a graph, or get inspired by a novel protocol, constraints of the format divert my attention to another topic, or worse, summon a brusque conclusion of the paper. I miss the quiet pause of turning over a page of a novel. It gives me time to comprehend, condense and calibrate the last dozen pages’ information in preparation for the next dozen. Reading a paper feels like sprinting: I hold onto all the facts the best I can, juggling multiple trains of thought, processing them as fast as I can, while simultaneously being introduced to new facts and information at the same time. By the time I finish, I feel exhilarated and accomplished, but I am always out of breath.

What I miss even more is the physicality of reading a book – scrolling through an article on my computer screen doesn’t pose the satisfying struggle of contorting my fingers into obtuse angles to fit a fat book into. Every paper I download feels no different from the last one. Tepid, freshly printed pages sit limp in my hands. No dog-ears or spines broken into to fit the shape of my palms. No linty residue left on my fingertips from powder-yellow pages. No musty smells nor coffee stains that recount its previous lives and muses. Even though what I currently read is greater in volume and diversity compared to my routine reading list, my thirst for wallowing in the satisfaction of reading a book till its last page and closing it shut to add it to my bookshelf remains unequivocally unquenched. For me, the act of reading extends beyond the definition of the word, and the physical, mechanical ritual of interpreting and unraveling the words off of a book held in my hands seems to be an integral part of this experience.

I have come to speculate that I feel like I haven’t “read” because of the intrinsic non-resolvable nature of scientific narratives, a property that science and experimentation as fields at large also share. No scientific narrative can ever have an uncontestable, resolved ending. No happily-ever-afters, but rather to-be-continueds, and to-be-challengeds. More queries are generated than questions answered, giving papers a sense of being complete and incomplete at the same time. A sense of insufficiency, that possibly doesn’t quite satisfy the classical conciliatory needs of a reader. 

Yet, reading in science feels like watching a good movie that never ends; it’s addicting nature fuelled by authors that never seem to stop writing. And as long as they keep writing, I will keep reading with a voracious appetite that seems to grow bigger and bigger, day after day, because the more I read, the less I seem to know.

 

MSc. Ashwathi P Menon
Aptamers
Center for Applied Medical Research

Member of the ENACTI2NG consortium

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October, 16 2018

To kill or not to kill

The human immune system has developed mechanisms to protect the body from various invaders, such as bacteria, viruses or parasites, which means we can fight off conditions like colds, the flu or food poisoning. Sometimes, however, the danger originates from within the body, as in the case of cancer. Cancer is a result of healthy cells undergoing changes, called mutations, which make them lose their natural function and divide uncontrollably.

Since cell mutations are relatively common, the immune system also learnt to recognise healthy self from mutated self. The immune system consists of many cell types with various functions. One of these cell types is the CD8 T cell. It can destroy cancer by recognising patterns present on surface of cancer cells, which are often a result of the cell’s mutations. T cells recognise cancer through a molecule called TCR, which is present on their surface. Through a molecule present on their surface, called the TCR, T cells recognise cancer cells. Each TCR recognises one particular pattern. As a result of their mutations, cancer cells can carry either mutated patterns (natural patterns that would not normally be present at that stage of the cell’s life) or normal patterns (regular patterns that exist in higher amounts than on regular cells). All these cases can potentially activate T cells containing this pattern-specific TCR. However, cancer cells can carry mutated patterns common for other cell types, and the immune system classifies these patterns as “self”, and therefore harmless. This means that when a T cell with a TCR highly specific for this pattern was created, it was silenced or even destroyed by the immune system, and only T cells with less reactive TCRs were kept alive. In the battle against cancer, this puts cancer at an advantage, since the cancer-specific T cells are not very good at recognising and acting against cancer cells. 

Nonetheless, this mechanism, with its strengths and defects, still exists in our body, and scientists have thought it possible to improve and use it as anti-cancer therapy. As Author described in a previous post, one such treatment is CAR therapy. Thanks to this, we can use T cells as the effector cell, but the TCR is partly replaced with a more powerful receptor. And while CARs have shown great promise so far, part of the research has focused on simply improving the TCR molecule itself. The idea behind TCR therapies is to find T cells containing cancer reactive TCR in patients with cancer and engineer these TCRs in the lab. Then, these reactive TCRs could be placed in the same patient’s T cells, or into T cells of patients that have no cancer specific TCRs. PlacasOnce expanded, the T cells would be returned to the patient and left to fight cancer. So far, this strategy has shown to reduce cancer load in several different studies, but compared to CARs, these T cells are less effective and don’t tend to survive long in the patient’s body. On the other hand, unlike CAR T cells, TCR engineered T cells can also recognise cancer patterns that are not necessarily present only on the surface of the cells, but also internally, making the range of possible cancer targets much broader.

In the Wooldridge T cell lab, part of our research focuses on improving current TCR therapies, but not through improving TCR molecules themselves. Alternatively, the aim is to improve a helper molecule present on T cells, called CD8 co-receptor, the function of which is to aid TCR recognition of patterns. With an improved CD8 molecule, the T cell could become more strongly reactive, even when the TCR is not highly sensitive to the cancer pattern.

metabolism

Immunotherapies are putting human T cells into focus as main fighters of cancer. While CAR T cells show great promise in targeting several different types, TCR therapies are battling cancers that CARs cannot necessarily target. The human immune system has been fighting these battles all our lives, so no matter the strategy, current immunotherapies have great potential to help the body fight internal dangers by slightly improving the mechanisms that already exist.

 

MSc. Lea Knežević
Faculty of Medical and Veterinary Sciences
University of Bristol

Member of the ENACTI2NG consortium

This email address is being protected from spambots. You need JavaScript enabled to view it.

 

 

May, 15 2018

Armoring the body against cancer

For over a century, an extensive part of biomedical research has been focused on understanding and fighting cancer, involving thousands of oncology experts around the world. Common treatments such as surgery, chemotherapy and radiotherapy have increased and improved the life of millions of patients. However, they are highly invasive and expose the patients to external substances which are harmful not only to cancer cells, but also to healthy ones. What if we could fight cancer from the inside instead of from the outside? This is exactly what the foundation of immunotherapy relies on. It strengthens the immune system and makes it capable to fight and suppress cancer.

Within immunotherapy, there is a novel type of treatment that’s having increasing success in clinical trials with patients suffering from a blood cancer type called leukemia. This treatment involves a modified immune cell called Chimeric Antigen Receptor (CAR) T cell.

Picture1

In this therapy, T cells, which are one of the main fighters of our immune system, are genetically improved by introducing an engineered component to gain the possibility of specifically attacking and killing cancer cells. This type of therapy was named by the American Society of Clinical Oncology (ASCO) “The 2018 Advance of the Year”.Picture2

One of the remarkable examples of the successful experiences with this therapy is the case of Emily Whitehead. She suffered from leukemia in an advanced stage with low survival expectancy. Emily was the first person to receive the CAR T cell therapy. She had the quickest response the doctors had seen in the shortest period of time. Emily has been free of cancer for more than 5 years.

Notwithstanding, if this therapy is so promising, what are the challenges now? Several, because unlike Emily, other patients have presented dangerous side effects as an overactivation of the immune system or alterations of the nervous system. The major ones are finding the balance between the activation and control of the immune system with the CAR T cells, discovering new targets to tackle in the cancer cells and making this therapy effective to other types of cancer besides leukemia. It is exactly in these points where a vast part of the research of immunology is focusing this year.

Multiple groups of experts around the world are addressing these challenges, like the European Network on Anti-Cancer Immuno-Therapy Improvement by modification of CAR and TCR Interactions and Nanoscale Geometry (ENACTI2NG). In this network, young scientists from around the world collaborate in universities located in Germany, Spain, the Netherlands, Austria and England, undertaking the challenges mentioned above.

One of the members of this consortium is the University of Freiburg in Germany, where the research is led by Professor Wolfgang Schamel and Dr. Susana Minguet. This project is attempting to modify the design of the engineered components in the CAR T cells, introducing new molecules that are related to the activation, survival and growth of the T cells. The idea is maintaining the activation of the immune system to fight cancer but at the same time reducing the side effects. During the next years, the first results will come to light.

Even though we still cannot predict how long it will take to design a therapy which can fight all types of cancer, the reality is that we are already living in a new era of cancer treatment: the CAR T cell therapy era.

 

MSc. Rubí Misol-Há Velasco Cárdenas
PhD Student on the improvement of CAR T cell therapy
Albert-Ludwigs-Universität Freiburg 

Member of the ENACTI2NG consortium

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Images from Juno Therapeutics and Parker Institute for Cancer Immunotherapy.