Winners of the second competition in the International Research Agendas Programme Winners of the second competition in the International Research Agendas Programme
Astrocent, an ultramodern centre for particle astrophysics
Gravitational waves, black holes, dark matter and the hidden Universe ? these are the questions to be explored by scientists working at Astrocent, a science and technology centre that is currently being set up. This sounds exciting, but the exploration of new phenomena, currently considered the most puzzling in physics, is not the only purpose for which the centre will be established. The advanced tools and devices required to probe the mysteries of physics and astrophysics will also find practical applications in cutting-edge technology and medicine.
Astrocent is an interdisciplinary international research centre, being founded in Warsaw by Prof. Leszek Roszkowski and Prof. Tomasz Bulik ? beneficiaries of the International Research Agenda (IRA) programme of the Foundation for Polish Science. The Astroparticle and Cosmology (APC) Laboratory, a world-class research institute based in Paris, will be Astrocent’s international strategic partner. The Nicolaus Copernicus Astronomical Center (CAMK) of the Polish Academy of Sciences and Warsaw University of Technology will be Astrocent?s Polish partners.
Astrocent’s primary objective will be to detect and study extremely weak signals and hidden information in physics, particularly in the studies of the Universe. Most of the Centre’s work will be related to experiments that are currently being planned to detect gravitational waves and dark matter. These are among the most fundamental, and at the same time most exciting, areas of particle physics and astrophysics. Unprecedented progress has been achieved in their understanding over the last few decades.
?Popular opinion notwithstanding, the Universe around us is not completely empty. On the contrary, we know that there is about five times more invisible, or dark, matter than there is ?ordinary? matter, of which the Earth and visible objects, such as stars, are composed. What we do not yet know is what this dark matter is,? says Prof. Leszek Roszkowski. ?Neither is the Universe entirely silent,? he adds. ?Extremely interesting data is constantly streaming towards us from space. However, to be able to decipher this information, we need to build highly sensitive instruments, as well as develop methods for separating interesting signals from the ocean of all kinds of noise and a deluge of data from already known astrophysical phenomena.?
This year’s Nobel Prize in physics has been awarded for such a ground-breaking achievement ? namely, the construction of the LIGO detector, which for the first time recorded gravitational waves. Gravitational waves are ?wrinkles? in space-time, caused by some event in the Universe. Their existence was predicted over 100 years ago by Albert Einstein. He believed, however, that they were merely the product of mathematical transformations of the equations of General Relativity. It was the Polish physicist Prof. Andrzej Trautman who showed half a century later that gravitational waves do exist and can be detected ? the result for which he was awarded the FNP Prize for 2017. Gravitational waves escaped detection, however, for a long time. They were finally detected for the first time in 2015 with the LIGO detector. In this case, the gravitational wave was the echo of a collision of two black holes, some 1.3 billion light-years from the Earth. Black holes are the final stage in the evolution of stars ? space objects whose mass is concentrated in such a small area that they collapse under the force of their own gravity. The gravity they generate is so strong that nothing can escape from it, not even light, and therefore they are perfectly black objects. The only sign of their existence is the powerful gravitational force they exert. However, there are other things currently happening in astrophysics apart from the first detection of gravitational waves in 2015. A second detection of gravitational waves was announced quite recently, in October 2017. This time, the source was the collision of neutron stars (objects of extremely high density), and the event probably took place in galaxy NGC 4993, some 130 million light-years from the Earth. The detection of this event is another breakthrough, made possible by the work of several hundred scientists, including Prof. Tomasz Bulik, a member of the VIRGO Observatory.
?The LIGO and VIRGO discoveries have opened a new window on an aspect of the Universe that has eluded observation until now. We expect to learn more about the nature of gravitational waves from the third-generation Einstein Telescope (ET), a 10-kilometre long underground interferometer, that is being planned in Europe. ?The Astrocent team will join the ET project,? said Prof. Leszek Roszkowski.
Another great experiment in which Astrocent will participate is the DarkSide-20k project, focused on identifying dark matter particles. ?It is generally believed that dark matter is made up of some unknown, massive and extremely weakly interacting elementary particle, however scientists are divided as to its specific properties. In order to resolve this issue, we need to discover the particle, and to do this we need extraordinarily sensitive equipment. With over twenty years of effort, their sensitivity has improved by a factor of one million, which is unprecedented in any field, not just physics,? says Prof. Leszek Roszkowski. The DarkSide-20k detector currently being designed will be another giant step in this race. It will be built in Gran Sasso in Italy in 2022, and will incorporate twenty tonnes of liquid argon.
?We are confident that Astrocent will contribute both to science and to the technological breakthroughs needed in both experiments. The practical experience gained in the process will be used in subsequent large-scale experiments in astrophysics, as well as in industry and medicine,? promises Prof. Tomasz Bulik.
At least three practical applications can already be foreseen for Astrocent’s technological advances. The first are smart algorithms for processing large amounts of data and selective extraction of important information. Both projects will generate unprecedented amounts of data, and this creates a challenge for us to develop tools for sorting and selecting it. Currently, other disciplines of natural science and medicine are also swamped with a deluge of data, and therefore it is very important to find a solution to this problem.
Another practical aspect of Astrocent’s research and development work will be the development of technology for photon detector modules based on silicon photomultipliers (SiPM). SiPM modules will be used in the measuring devices required to explore the hidden Universe, but they will also have a wide range of applications in medicine (eg. PET scanners, gamma cameras, mammography), industry and power engineering. ?The development of SiPM technology in connection with the construction of a new PET scanner by Professor Moskal?s team at the Jagiellonian University seems particularly promising. The team has already expressed interest in cooperating with Astrocent,? said Prof. Leszek Roszkowski.
The construction of seismic sensors is another area in which Astrocent hopes to make a contribution. Sensors of this kind are used in gravitational wave detectors, such as the LIGO, but they can also find commercial applications, for example in the search for oil deposits or in earthquake early warning systems.
?It is also important that Astrocent will bring together specialists in several disciplines: physicists, computer scientists, engineers and technicians. These teams will work together, sharing the most advanced results in their respective fields of expertise. This kind of close cooperation will be a new development in Poland and could lead to a real breakthrough,? argues Prof. Tomasz Bulik.
Who are the founders of Astrocent?
PROF. LESZEK ROSZKOWSKI, PhD ? physicist, graduated in physics from the University of Warsaw, obtained his PhD from the University of California, Davis and his post-doctoral degree (habilitacja) from the Jagiellonian University. He also works at the Department of Physics and Astronomy at Sheffield University in the UK. He returned to Poland in 2011 as a recipient of FNP’s Welcome award. He is the initiator and chairman of the international COSMO conference series, a member of international advisory committees of the COSMO, IDM and DARK conferences, and a member of the editorial board of the journal Reports on Progress in Physics. Currently he holds the position of the chair of the National Board for Particle Astrophysics. He is also a frequent guest at CERN near Geneva. He is mainly interested in dark matter and, more broadly, in elementary particles as the solution to the mystery of dark matter, the Higgs boson and the new physics ?beyond the Standard Model?.
PROF. TOMASZ BULIK, PhD ? astronomer, graduated in physics from the University of Warsaw, obtained his PhD from Penn State University and his post-doctoral degree (habilitacja) from the Nicolaus Copernicus Astronomical Centre of the Polish Academy of Sciences; he has also worked at the University of Chicago. He is currently deputy director at the Astronomical Observatory of the University of Warsaw. He is a member of the VIRGO-POLGRAW team, which looks for evidence of gravitational waves in the LIGO/VIRGO experiments, and contributes to the work of the HESS/CTA observatory. He won the prestigious Breakthrough Prize and is an active populariser of astronomy. He is mainly interested in theoretical astrophysics and neutron stars.
ReMedy ? new solutions in civilizational disease diagnostics and therapy
We live under constant stress. Similarly, our body cells are continuously exposed to various stress factors. Psychological stress and cellular stress are two different things, however. Cellular stress is a condition where the cell is affected by various unfavourable factors, such as free radicals, high temperature, radiation, pathogens, the presence of certain substances, or simply the ageing process. In such a situation, the cell either dies or triggers a sequence of internal processes as a result of which it is able to adapt to new conditions. Interestingly, these processes often lead to greater resistance to stress and to increased vitality of the cell. Can these natural intercellular processes, therefore, be harnessed to design new drugs?
Professor Agnieszka Chacińska and Professor Maria Magda Konarska, winners of the second competition in the International Research Agendas (MAB) programme, funded under the Smart Growth Operational Programme, are convinced that they can. In order to develop more efficacious therapy forms and methods of fighting contemporary civilizational diseases using the cellular adaptation mechanisms, both researchers will open a new interdisciplinary research unit ? ReMedy ? at the Centre for New Technologies at the University of Warsaw. They have obtained PLN 35 million for that purpose from the Foundation for Polish Science. The Medical University of Göttingen will be the foreign partner institution for the project. The German partner will not only offer research support, but also ? even more importantly ? will supply the organizational model and help in networking with the industry, which is essential for product marketing. ?The new entity, which will be created as part of the ReMedy project, will bring together excellent researchers and will focus on comprehensive and mutually complementary studies of living organisms, whose goal will be to understand stress-induced cellular adaptation on a molecular and biochemical level and its use to fight diseases in humans,? says Professor Magda Konarska, Deputy Director of ReMedy institute.
?Our existing knowledge about living cells and organisms is quite fragmented. Therefore, many devastating diseases still remain incurable. In the ReMedy programme, our goal is to understand the holistic function of cells, focusing on molecular and cellular processes and their reconstruction under stressful or pathological conditions, in order to be able to offer new therapies. By establishing the new institute, we hope to create a vibrant centre for researchers and scholars to promote creativity, innovation and collaboration, while maintaining the highest scientific and organizational standards and ensuring productivity. We believe that collaboration is the key to success, along with unified efforts by various individuals with diverse interests and expertise,? adds Professor Agnieszka Chacińska, ReMedy Director.
The results of research work to be carried out at ReMedy are expected to have practical applications in two areas of public health which currently represent the greatest medical and social challenges in developed countries. The first area is that of currently untreatable agerelated and neurodegenerative diseases and pathologies. The other one is cancer. As regards neurodegenerative and age-related diseases, their underlying cause is a disruption of the homeostasis (balance) of proteins in the cells and damage to mitochondria. The knowledge acquired at the ReMedy institute will make it possible to activate internal regenerative molecular and biochemical pathways which will prevent and/or revert age-related neurodegeneration. The opposite is the case with cancers ? cancer cells are highly resistant to stress, which makes them very durable. This property is destructive for the body and often leads to death. The knowledge acquired as a result of the studies to be undertaken at ReMedy will open new avenues for treatment strategies consisting in blocking the adaptation pathways opened in cancer cells.
In summary, a holistic and systemic overview of the cellular stress response will translate into important discoveries, making it possible to apply for patent protection and to introduce new effective therapies into the market.
Who are the founders of ReMedy?
AGNIESZKA CHACIŃSKA ? Ordinary Professor of Biological Sciences and Head of the Mitochondrion Biogenesis Laboratory at the Centre for New Technologies at the University of Warsaw. In her research work, she has mainly focused on the biogenesis of mitochondria and the role of this process in cellular health and disease. She graduated in Biology from the University of Warsaw, specializing in Molecular Biology. She defended her Ph.D. and habilitation theses at the Institute of Biochemistry and Biophysics of the Polish Academy of Sciences. She has worked at the University of Basel in Switzerland, at the Max Planck Research Institute in Halle, Germany and at the University of Freiburg in Germany. Between 2009 and 2017 she worked at the International Institute of Molecular and Cell Biology. She is a corresponding member of the Polish Academy of Sciences and winner of several prestigious scholarships and research awards, including: The Prime Minister Award, Nicolas Copernicus Science Award , the Award of the Minister of Science and Higher Education, and the Award of the President of the Polish Academy of Sciences. She has authored more than 70 publications in international research journals and has been cited more than 4,000 times.
MARIA MAGDA KONARSKA ? a University of Warsaw Professor; since 2015 she has been Head of the RNA Biology Laboratory at the Centre for New Technologies at the University of Warsaw and Professor Emeritus of Rockefeller University in New York, USA, where she spent 26 years as the head of the Molecular Biology and Biochemistry Lab. She specializes in researching the function of RNA in cellular processes and in particular in the pre-mRNA splicing mechanism. She graduated in Genetics from the University of Warsaw and was later awarded the Ph.D. and habilitation degrees at the Institute of Biochemistry and Biophysics of the Polish Academy of Sciences. During her scientific career she has worked for such institutions as the Center for Cancer Research of the Massachusetts Institute of Technology in Cambridge, USA and Rockefeller University in New York. She is a corresponding member of the Polish Academy of Sciences and winner of numerous Polish and international scholarships, grants and research awards. She is the author of 59 publications in international research journals and has been cited more than 5,800 times.
International Centre for Cancer Vaccine Science
Although still in its infancy, immunotherapy in cancer treatment has already been hailed as the next revolution in medicine. It seems to be for oncology what antibiotics and preventive vaccination have been for the treatment of infectious diseases. Thanks to those scientific advances, we saw the back of many, previously lethal, diseases. Will the same happen to cancer thanks to immunotherapy and to the widespread use of personalized therapeutic cancer vaccines?
Large-scale comprehensive research into such immunotherapies, followed by their commercialization and implementation into clinical practice, will be the purpose of a new scientific facility which is currently being built in Gdańsk ? the International Centre for Cancer Vaccine Science. The centre has been established by experienced researchers: Theodore Hupp from the UK and Robin Fahraeus from France ? selected in the second competition under the International Research Agendas (MAB) programme implemented by the Foundation for Polish Science (FNP), using funds from the Smart Growth Operational Program. PLN 41 million in funding for the project has been secured. The new facility will be based at the University of Gdańsk and will be created in collaboration with the University of Edinburgh.
The fundamental idea behind oncological immunotherapy is straightforward ? the goal is to kick-start cancer patients? immune system to fight the neoplasm. Cancer cells are generated in the human body every single day. The transformation of a healthy cell into a cancer cell is triggered by DNA defects. Mutations are enabled by inflammation, infection, solar irradiance, tobacco smoke, environmental pollution or free radicals, which find their way into the body along with food. The immune system is generally able to quickly recognize a mutated cell and to eliminate it. However, sometimes the immune system lets certain hazardous agents slip by, permitting the rogue cell to proliferate. The growing cancer structure applies a range of strategies to stay off the immune system?s radar. Cancer cells escaping the immune supervision are one of the most important mechanisms which enable cancer to progress. Restoring control offers a great opportunity to defeat cancer. Hence, the prestigious Science journal, as well as the American Society of Clinical Oncology (ASCO) recognized cancer immunotherapies as the greatest breakthrough in recent years, not only in medicine, but also in science as a whole. ASCO experts also believe that immunotherapy is set to replace other cancer therapies quite soon and that one in every two cancer patients will undergo immunotherapy as soon as in 2020. It seems that immunotherapies might make it possible to fully cure even advanced-stage cancers, as well as metastasized and chemotherapy-resistant neoplasms.
Cancer immunotherapy can currently be divided into specific and non-specific therapies. Non-specific therapies activate the immune system to fight a particular type of cancer, working in an identical way for all patients suffering from the same type of cancer. This is the operating principle of immune checkpoint inhibitors (such as ipilimumab, pembrolizumab and nivolumab), which have already been shown to be effective in the treatment of melanoma and lung cancer. A number of trials are underway to evaluate the efficacy of the drugs in the treatment of kidney, colon, prostate, breast, head and neck cancers, as well as other tumours.
Specific immunotherapy, on the other hand, rallies the immune system to fight a particular cancer detected in a specific patient. The most dynamically developing area of specific immunotherapy are customized therapeutic cancer vaccines (contrary to infectious disease immunization, these are not preventive vaccines inhibiting the development of a disease, but are rather used to actively treat existing patients). Each vaccine is prepared individually for a concrete patient on the basis of specific neo-antigens, i.e. proteins, which occur only and exclusively in that particular growing tumour, depending on a unique combination of genetic mutations carried by the cancer cells present in a specific patient. Latest advances in genetics and molecular biology (such as sequencing) are used to identify neo-antigens, coupled with bioinformatic algorithms and computer modelling. A customized vaccine designed and produced to fight neo-antigens identified at the lab, once introduced into the patient?s body, recognizes the neo-antigens and triggers a powerful cascade of natural defence mechanisms geared towards fighting the neoplasm. Importantly, preliminary research suggests that a vaccine therapy aligned with the genetic properties of the cancer does not cause any important adverse reactions. This is because the vaccines are precisely targeted to act in the neoplastic focus, without damaging any of the neighbouring tissues or organs.
?These exciting advances have shown that immunotherapy drugs can become precise personalized medicines with a broad range of applications in the treatment of various types of cancer. At the University of Gdańsk, we plan to build an interdisciplinary centre specializing in cancer vaccine research. We intend to recruit, inspire and teach the next generation of researchers and medical doctors who wish to work with increasingly better oncological therapies. We would like to involve leading international advisors in our research, including both partners from the University of Edinburgh and from Polish research institutions,? says Professor Theodore Hupp, director of the new centre. The overarching idea is to develop innovative targets and control points for immunotherapy based on neoantigens. In collaboration with the industry, these will be used to design vaccines to be used in clinical practice.
Founders of the International Centre for Cancer Vaccine Science
THEODORE HUPP (aged 55) ? an American who is currently working in the UK as head of the Experimental Cancer Research Centre of the University of Edinburgh. He graduated in Chemistry from Ohio State University and received his Ph.D. in Biochemistry at Michigan State University. In later years, his main research interests included proteomics and proteogenomics, as well as immunosuppression caused by cancer and the role of different signalling paths in oncogenesis. He has been the main applicant or co-investigator in 25 research grant programmes funded by, among others, the Medical Research Council (MRC-UK), Biotechnology and Biological Science Research Council (BBSR-UK), Cancer Research UK and AICR (Association for International Cancer Research). Besides his excellent research qualifications, he has vast experience in the area of intellectual property and in collaboration with the industry.
ROBIN FAHRAEUS (aged 57) ? a Swedish national, currently working as head of the research group of the French National Institute of Health and Medical Research (INSERM). He also serves as scientific advisor to the French National Cancer Institute (INCa). He obtained his Ph.D. in Cancer Biology from the Karolinska Institute in Sweden. During his scientific career he has worked at the University of Dundee in the UK, as well as the Masaryk Memorial Cancer Institute in Brno, Czech Republic. He is a laureate of many prestigious scholarships and awards.
Photos: Professor Agnieszka Chacińska, Professor Magda Konarska, Theodore Hupp and Robin Fahraeus: One HD.