Dr. Magdalena Weidner-Glunde and PhD student Mamata Savanagouder featured as experts in the documentary series „Virus Hunting”

„They are mistakenly seen as a companion only to the cold months (…) Some cause harmless infections, others are a deadly threat,” these words begin the documentary series „Virus Hunting”, which takes a closer look at the achievements of scientists working on the front lines of the fight against viral diseases. The first episode of the series featured Dr. Magdalena Weidner-Glunde, head of the Laboratory of Molecular Microbiology and Virology at our Institute, and Mamata Savanagouder, a PhD student in her team.

Dr. Weidner-Glunde explains what the virus is and why cytomegalovirus research is being conducted at the Institute.

The virus is the kind of package that is supposed to reach the cell and allow the virus to multiply there. This package on the outside has a protein envelope, the so-called capsid, which protects the genome inside. Once inside the cell, this genome is released and allows the virus to replicate, multiply and create new viral particles. – Dr. Weidner-Glunde explains in the episode.

Cytomegalovirus in most cases in healthy people does not cause major problems or strong symptoms, possibly mild cold symptoms. It becomes a problem if the infection occurs in a pregnant woman, because the most common result is partial or total hearing loss in the fetus, later in the newborn. In addition, the problem is that in many cases children are born healthy and only lose their hearing after some time. – she adds.

We encourage you to watch the first episode of the series „Virus Hunting”.

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Spring is coming, so turn your face to the sun and grab some vitamin D

After the autumn-winter period, our body needs vitamin D. Scientists have proven that even a balanced and varied diet is not enough to provide the total daily dose of this vitamin, because skin synthesis is its main source for the body. That’s why they advise you to expose your face to the sun in the spring and catch some vitamin D.

The latest recommendations for the prevention and treatment of vitamin D deficiency in children and adults in Poland have been developed by a team of scientists representing Polish and international medical societies and national specialist consultants. Their consensus, by Prof. Paweł Płudowski and the whole team has just been published in the journal „Nutrients” (https://doi.org/10.3390/nu15030695).

The development of the current guidelines was supported by prof. Carsten Carlberg, researcher of vitamin D, currently the leader of the scientific group dealing with nutrigenomics at the Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences in Olsztyn.

„We cannot rely on diet as the only source of vitamin D – even a balanced and varied one is not enough, so in the autumn and winter everyone should supplement vitamin D” – indicated Prof. Carlberg as the most important message of the publication.

The most well-known action of vitamin D is to maintain an adequate level of calcium in the body to maintain normal bone structure. „This is the main reason why every child should be supplemented with vitamin D from birth – both in winter and summer. In addition, vitamin D is important for training our immune system to work effectively against microbial infections, but not overreacted to possible autoimmune reactions” – explained Prof. Carlberg.

Long-term vitamin D deficiency can lead to bone diseases – rickets in children and osteomalacia in adults. „Vitamin D deficiency also causes malfunction of the immune system, leading to increased susceptibility to infectious diseases or autoimmune diseases” – the researcher pointed out.

Prof. Carlberg added that for the average Pole, the level of vitamin D (i.e. the level of 25-hydroxyvitamin D3 in the blood serum) determining the deficiency is defined below 50 nM (20 ng/ml), although each person is characterized by a different sensitivity to vitamin D.

It has been scientifically proven that even a balanced and varied diet is not able to provide the total daily dose of the body’s demand for vitamin D, because its main source is skin synthesis in contact with UV radiation. However, as the scientists pointed, spending a lot of time indoors, wearing clothes and using sunscreens, as well as low intensity of solar radiation in the autumn and winter months, translates into numerous vitamin D deficiencies during this time.

Therefore, a well-chosen supplementation is crucial. „I suggest choosing the dose of the daily requirement based on body weight – if you weigh up to 75 kg, take 2000 units daily (in the autumn and winter), and if more – 4000 units (but not more; this is the maximum dose)” – advises Prof. Carlberg.

In turn, in the spring and summer months, from April to September, it is worth exposing the skin to the sun (remembering about adequate protection against sunburn). „The time of day is important. Two hours before and after the sun’s zenith (11am-3pm in summer time) are most effective. During this time, 20-30 minutes of exposure of the face and bare shoulders should be enough. Of course, avoiding sunburn each time ” – said Prof. Carlberg.

The scientist added that people who do not spend enough time outdoors even in summer should supplement vitamin D throughout the year.

In the developed guidelines, experts pay particular attention to the need for education in the field of vitamin D supplementation for preventive purposes, addressed primarily to medical societies, medical personnel and decision makers responsible for health policy. They also postulate the inclusion of practical tips on the prevention and treatment of vitamin D deficiency in everyday practice.

 

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Scientists visit the Olsztyn Planetarium

Another extraordinary meeting with the Olsztyn Children’s Academy is behind us. This time the young students were met by Dr. Anna Szóstek-Mioduchowska, who talked about an issue of particular importance in the autumn-winter season – the immune system. Dr. Szóstek-Mioduchowska drew attention to the human body’s 'tools’ for defending itself against harmful external and internal factors. What immune cells do we find in the human body and how many are there in one drop of blood? What is the difference between innate and acquired immunity? What does the body tell us when we are affected by ailments characterised by inflammation? Answers to these and many other questions were sought during the meeting.

The students were also treated to a workshop session where they could play young chemists’ roles. Under the supervision of Kamila Penkacik, M.Sc., the children studied magical antioxidants and created molecular pearls.

The third meeting of the Academy took place on 11 February at Olsztyn’s Planetarium. The next is planned for 15 April. More information about the Olsztyn Children’s Academy can be found on the Planetarium website under the Education tab.



 
 

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The Genome above the Genome – Prof. Carsten Carlberg, ERA Chair WELCOME2

Our daily diet contains carbohydrates, lipids, proteins, minerals, and vitamins – nutrients that provide us with energy and serve as the building blocks of our bodies. However, we are increasingly learning that what we eat also interacts with the genes in our cells in important ways.

Diet is the most dominant of the environmental factors affecting us from conception to death. Every day, more than 1 kg of food passes through our bodies, the largest amount of all substances we come into close contact with. Dietary signals are in direct contact with the genome: every day, our breakfast, lunch, and dinner “talk” to our genes. For more than 20 years, we have known the sequence of all 20,000 human genes that carry the information needed to build proteins. We also know that in addition to them, there are at least as many non-coding RNAs within our genome, which do not produce any proteins. This understanding has brought us into the postgenomic era, where research has been initiated in numerous new fields. These include nutrigenomics, which can be defined as the study of how the food we eat (“nutri”) interacts with all of our genes (“genomics”).

The same yet different

Nearly 99% of the genome differs very little among all 8 billion humans on Earth. However, we do differ from one another in terms of such obvious traits as height, weight, hair, and skin and eye color, as well as such characteristics as the likelihood of developing a specific disease. Some of these traits, such as eye color, are obviously determined by genes. However, the risk of developing type 2 diabetes, for example, is only up to 10% determined by the genes we inherit from our parents and up to 90% determined by environmental factors and our lifestyle.

Our body is made up of 3×1013 cells, which come in at least 400 different variants. They form the tissues of the brain, the immune system, the liver, and all other organs in the body. In every human, each cell contains the same genome, which means the same information necessary to build proteins. In different types of cells, however, the genome is organized by proteins into tightly packed chromatin (called heterochromatin) and lightly packed chromatin (euchromatin) in such a way that access is only possible to those genes that carry information about the proteins needed in specific tissues. This packing of the genome, which does not affect its DNA sequence (it does not cause any mutations), is referred to as the “epigenome” (“epi-” meaning “above”).

Some aspects of the epigenome become fixed already in the first weeks of gestation, referred to as early embryogenesis. In this very sensitive period of life, important decisions are made about the development of organs, which should remain unchanged for the rest of the organism’s life. It is this stable part of the epigenome that ensures that our brain cells remain brain cells throughout our lives, instead of “changing their minds” and suddenly transforming, for example, into kidney cells that produce urine. The integrity of the human body is based on the stability of this aspect of the epigenome.

But the epigenome has also certain dynamic aspects: signals from the inside and outside of cells affect the ability of specialized proteins in the nucleus to recognize certain regions of the genome. Certain signals, for example those from food components, can alter how the genome is packaged into euchromatin and heterochromatin. Genes located in euchromatin can be recognized by transcription factors and RNA polymerases. This means that a specific cell uses only those of the 20,000 genes that it can access through the chromatin structure. This means an average of 10,000 genes that get copied out into RNA (in a process called transcription), which is used by a particular cell as a “template” to synthesize proteins. Changes in the epigenome can affect the transcriptome, or the total number of RNA molecules in our cells. Many of the signals that affect the epigenome and the transcriptome come from diet. Therefore, a central aspect of nutrigenomic research involves describing and understanding how nutrients affect the epigenome and the transcriptome of cells, and by the same token their functions. This aspect of nutrigenomics is often referred to as nutritional epigenomics.

Every day, the dietary choices we make impact on the epigenome and the transcriptome in our tissues and cell types. A disease like type 2 diabetes takes years or even decades to develop, but it results above all from daily diet and lifestyle choices. In a similar way, other elements of what is called the metabolic syndrome, such as high blood pressure, abdominal obesity (measured by waist circumference), high levels of fat (triglycerides), and low levels of HDL (high-density lipoprotein, also referred to as the “good” cholesterol) in the blood, depend on the decisions we make – what we eat and how much we exercise.

Benefits of vitamin D3

The compounds that can “talk” to the epigenome include vitamin D3. In fact, this is a nutrient we are able to produce within our bodies, through skin exposure to UVB radiation from the Sun. However, predominantly indoor lifestyles, skin coverage with textiles, the use of sunscreens, as well as the insufficient intensity of sunlight in the winter months mean that many people acquire vitamin D3 deficiency. Vitamin D status is measured by the blood serum concentration of the most abundant vitamin D3 metabolite, namely 25-hydroxyvitamin D3 (abbreviated 25(OH)D3). According to the US-based Endocrine Society, vitamin D status should be at least 75 nM (ideally 100 nM), whereas concentrations of 25(OH)D3 below 50 nM are regarded as deficiency, and below 30 nM as severe deficiency. More than 1 billion people worldwide have vitamin D deficiency. To put this into perspective, the average vitamin D status in the population in Poland is estimated at 46 nM, which means that many people in the country suffer from a deficiency of this compound and require supplementation, especially in the winter months.

However, one might ask whether the threshold level for the vitamin D status is the best benchmark for calculating the demand for vitamin D in individual people. Every human is different, and the impact of vitamin D on the response of the epigenome and the transcriptome in our cells will vary. Based on our concept of the vitamin D response index, people can be divided into high, mid, and low responders to vitamin D. It is estimated that one in four people fall into the group of low responders. This therefore means that we have our own individual requirements for vitamin D3 supplementation, especially during the winter months. High responders have lower needs and are likely to manage with the generally recommended, yet low concentrations: up to 20 μg, or 800 international units (IU) per day. Low responders, on the other hand, may need up to 4,000 IU (100 μg) per day.

Vitamin D is well known for its role in controlling calcium levels in blood. It is essential for bone remodelling; a process takes place throughout our lives. Children with vitamin D deficiency can develop rickets, and adults can be affected by osteomalacia, a deformation of the bones that carries a higher risk of fractures. In addition, vitamin D is extremely important for the proper functioning of the immune system, which comprises innate and adaptive immunity. The innate immune system is the first line of defence against microbial pathogens such as bacteria and viruses. In addition, cells of the innate immune system, such as monocytes, macrophages, and neutrophils, are key mediators of inflammation. Inflammation can be divided into acute and chronic. Acute inflammation lasts up to two weeks and supports the body in the fight against pathogens. In chronic inflammation, the cause of this harmful state is not removed successfully, and adverse reactions continue for months, years, or even decades. Most of the serious diseases, such as type 2 diabetes, atherosclerosis, Alzheimer’s disease and cancer, are associated with chronic inflammation. In the short term, vitamin D supports acute inflammation, but in the long term, it counteracts chronic inflammation. This chiefly happens through the “programming” of the epigenome and the transcriptome of monocytes and macrophages. These epigenetic programming events create cellular memory, which means that cells remember what they were exposed to. In a similar way, all the cells in our bodies (not just the neurons in the brain) can remember lifestyle-related events, such as daily responses to food components, physical activity, and exposure to pathogens.

A step towards personalized medicine

Our projects are based upon the central assumption that vitamin D trains immune cells and other tissue cells so that they can better respond to various environmental factors. In the context of the Horizon 2020-funded ERA Chair WELCOME2 project, we will be conducting an intervention study. Sixty volunteers with early signs and symptoms of metabolicsyndrome will be asked to make significant lifestyle changes for a period of three months. We will ask them to increase their average daily physical activity, for example by increasing the number of steps per day to at least 10,000. We will simultaneously give all participants vitamin D until they reach a very good status of 100 nM. In addition, we plan to follow up 10 highly committed participants for a period of three years and take their blood samples every three months. We will use their immune cells (obtained from the blood samples) to characterize their epigenome and transcriptome and observe how they change together with lifestyle changes. In this way, we will collect huge amounts of molecular data from each participant. We will analyse such data using bioinformatics methods, including machine learning.

A key point of our project will involve the development of computer models called digital twins. The concept of a “digital twin” is well-known in engineering, for example in aircraft construction. It stands to reason that all aircraft components, such as engines and wings, must undergo extensive tests, both individually and in combination with other components, to ensure that the aircraft will pose no risk to the pilot and passengers. Such tests are currently carried out using digital computer models, which can simulate a much broader range of conditions than traditional wind tunnels. Digital twins of real people are a lot more complex than aircraft engines. Therefore, it is necessary to be realistic and strive to model only certain tissues and cell types. Consequently, we will create digital twins of monocytes and lymphocytes isolated from blood samples taken from specific participants. Unlike other tissues in the human body, such immune cells have one advantage: they are mobile. Monocytes and lymphocytes circulate through the body, communicating with all organs. As a consequence, immune cells respond to all changes in the body and, supported by vitamin D, train their epigenome accordingly.

Importantly, digital twins not only facilitate computational descriptions of cell functions, but also offer the ability to test such factors as stress, infections, and exposure to food components. As with aircraft engines, we can also try out various interventions in silico, which means testing multiple factors in a computer model without the need to involve study participants. This means reducing their effort and exposure to danger, and saving funds. Since each individual is different, our digital twins will be idiosyncratic in nature, too. Consequently, we expect to obtain personalized recommendations for lifestyle changes for each study participant to reduce the risk of the development or progression of the metabolic syndrome. Since some of the conclusions from the modelling of these digital twins will be general in nature, we will attempt to apply the results we will obtain in the study to the general population.

This article was originally published in ACADEMIA – The magazine of the Polish Academy of Sciences | 2022 | No 3 (75) Turning Points

 

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Publication by Dr. Agnieszka Wacławik’s team selected as Editor’s Choice

The publication by the team of Dr. Agnieszka Wacławik from the Department of Hormone Mechanisms, entitled „Novel role for conceptus signals in mRNA expression regulation by DNA methylation in porcine endometrium during early pregnancy” by P. Kaczyński, V. van der Weijden, E. Goryszewska-Szczurek, M. Baryly, SE Ulbrich and A. Waclawik, was selected as ’Editor’s choice’ in the prestigious journal Biology of Reproduction 2023, 108(1): 150-168.

’Edtitor’s choice’ publications are articles that have made a significant contribution to a field of science. The selection of an article as an 'Editor’s choice’ recognises the authors’ work and highlights the importance of their research in the field of reproductive biology.

Dr. Piotr Kaczyński and the authors mentioned above have described a novel mechanism of embryonic effects on processes related to methylation changes in DNA sequences that may regulate the expression of genes in the endometrium that are important for the development of pregnancy. The findings, published in the journal Biology of Reproduction (2023, 108(1): 150-168, doi: 10.1093/biolre/ioac193), were produced within the framework of the NCN OPUS project (2017/27/B/NZ9/03014) under the direction of Dr. Agnieszka Wacławik, carried out at our Institute and during the internship of Dr. Piotr Kaczyński in the team of Prof S. Ulbrich at the ETH Zurich.

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Evolution, human migrations, and vitamin D deficiencies

When did organisms learn to synthesize vitamin D? How did its functions change throughout our evolution, and how did this affect the entire Homo sapiens species? Professor Carsten Carlberg answers these questions in his latest scientific publication.

A new publication by Prof. Carsten Carlberg, ERA Chair in the WELCOME2 project at the Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, titled „Vitamin D in the Context of Evolution,” has appeared in the journal Nutrients. The „career” of vitamin D goes back to as early as 1.2 billion years ago, when eukaryotes (organisms with cell nuclei) developed the ability to synthesize sterols (and therefore vitamin D). In his publication, Prof. Carlberg explains how in the course of evolution – including that of the Homo sapiens – the role of vitamin D changed over time and „stabilized” relatively recently.

 It wasn’t until 100 years ago that vitamin D was called a „vitamin” because its administration could cure experimentally induced rickets in dogs and rats. Rickets is also a developmental disorder in children, and many studies have linked vitamin D to calcium homeostasis and bone remodeling. It quickly became apparent that this is only one of many processes controlled by this micronutrient – others include detoxification, energy metabolism, and innate immunity. Researchers also point to a possible role for vitamin D in skin lightening among migrating peoples, particularly in European populations.

How did vitamin D become a vitamin?

Evolution is the basic process responsible for the biological development of all living organisms. There are no animals or plants on Earth that are not subject to the laws of evolution and thus do not adapt to environmental changes. In Prof. Carlberg’s paper, we read that one such adaptation was the development in animals ca. 550 million years ago, the Vitamin D Receptor (VDR), which transports proteins and enzymes for vitamin D metabolism.

Initially, vitamin D regulated physiological processes, the first of which was detoxification and energy metabolism. Thus, vitamin D modulated the energy-intensive processes of the innate immune system in its fight against microbes. In his latest work, Prof. Carlberg mentions that about 400 million years ago, species left the ocean and were exposed to gravity. Vitamin D took on the additional role of a master regulator of calcium homeostasis, essential for a stable skeleton.

„In its evolutionary origin in East Africa, the Homo sapiens species was exposed to extensive UV-B radiation every day all year round, which induced sufficient vitamin D3 synthesis. Therefore, over 200,000 years, humans have become accustomed to a consistently high vitamin D status of 100 nM 25(OH)D3 or more. Over the past 50,000-75,000 years, migration toward regions with latitudes above 37oN has allowed them to experience seasonal changes in sun exposure and periods of the year when vitamin D3 cannot be produced endogenously,” according to Prof. Carlberg’s publication.

As a result of the industrial revolution, people have adapted to an urban lifestyle with predominant work and indoor activity. Both conditions – winters with vitamin D and indoor preferences – often led to vitamin D deficiency in industrialized countries. In the 19th century, rickets was common among children in England, and vitamin D deficiencies increased tuberculosis in many countries. In a published paper, Prof. Carlberg concludes that it was not evolution but human migrations and lifestyle changes that made vitamin D3 a vitamin.

Quite recently – on an evolutionary scale – human lifestyle changes have caused a decrease in endogenous vitamin D3 production. At the same time, most of the population is not based on a Mediterranean diet, so they are vitamin D deficient. Worldwide, this problem affects over a billion people and causes numerous health problems, including bone deformities and reduced immune system performance.

Prof. Carlberg’s unique publication

This work by Prof. Carlberg sheds new light on the evolutionary mechanisms that led to the development of the VDR receptor, enabling vitamin D uptake. He also shows that it is not the evolutionary process but lifestyle changes and frequent migrations that are the reason for the vitamin D deficiencies occurring around the world today, which affect most of us.

The paper, „Vitamin D in the Context of Evolution,” also allowed Prof. Carlberg to cross another critical threshold: reaching H-index 60 on the Publons platform. It provides a service for scientists to track, verify and present their scientific reviews and editorial contributions to scientific journals. It is worth mentioning that Prof. Carlberg already has 265 publications on Publons, which have been cited nearly 12,000 times.

Prof. Carlberg’s main task within the ERA Chair WELCOME2 project at the Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences is to create a team dedicated to analyzing gene regulation on the scale of the entire human genome, in particular changes in the human epigenome. This will be aided, among other things, by the development of „digital twins,” or virtual models of healthy and sick individuals, allowing in silico (via computer simulation) testing of interventions related to diet selection, physical activity, and drug use. These activities will form the basis of the Center of Excellence in nutrigenomics at the Institute. You can read more about the ERA Chair WELCOME2 project here.

 

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Mealtless Monday #AnnualFoodAgenda – photo and video

„Meatless Monday” stands for an international campaign that encourages people to reduce meat in their diet for their health and the health of the planet. The production of animals has a significantly bigger environmental imprint than that of plants. It requires more energy and water, contributes to increased greenhouse gas emissions, deforestation, habitat destruction and species extinction. The biggest changes are made with small, yet regular, steps, hence the idea to stop eating meat al least once a week. And since we love fresh starts when it comes to dietary resolutions, Monday couldn’t be a better choice for this. On December 13th EIT Food #AnnualFoodAgenda in Poland joined celebrations and promotion of a plant-based cuisine and invited consumers for a unique culinary experience where they could prepare traditional japanese dish in a slightly avant-garde, since plant-based, version.

The event started with morning sessions addressed to school students and their teachers. The participants, mentored by professional chefs, got their hands on preparing plant-based lunch versions they could easily replicate at homes and take to school. These included vegetable pastas, spinach dumplings and plant-based alternatives to American street food. The students discovered the value of ‘green’ products for their health and learnt how their little everday choices could actually influence the well-being of our planet.

The evening workshops „Meatless Monday: Vege Sushi” was a great opportunity to discover one of the most healthy cuisines in the world and gain some practical skills needed to prepare its flagship dishes. The partcipants had a chance to exchange experiences, learn about the value of plant-based alternatives, interact with food researchers and, most importantly, co-create healthy meals that could be a part of their daily menus. Every workshop session ended with the participants sharing the meals prepared together, talking about the value of this experience to them and making resolutions for their on „Meatless Mondays”.

#Annual FoodAgenda is a communication project under the support of EIT Food. EIT Food is Europe’s leading food innovation initiative, working to make the food system more sustainable, healthy and trusted. The initiative is made up of a consortium of key industry players, startups, research centres and universities from across Europe. It is one of eight Innovation Communities established by the European Institute for Innovation & Technology (EIT), an independent EU body set up in 2008 to drive innovation and entrepreneurship across Europe.





































 

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​Committed to Sustainable Agriculture

Agriculture has been part of our lives for more than ten thousand years. Agriculture feeds us, supplies us with raw materials and draws our landscape. It is an essential economic activity for our development and shares the same challenge with society: Sustainability.

 

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