Prof Gliszczyńska: - Chemistry is the key to understanding living organisms

In your habilitation thesis, you looked at biomodification of compounds towards their anti-cancer activity. What does a chemist bring to medicine and what do they need to learn if they want to conduct research in this particular area?

An excellent reflection of what a chemist can contribute to medical science are the biographies of eminent scientists. Louis Pasteur made an important contribution to the development of bacteriology and virology, radioactive elements discovered by Marie Skłodowska-Curie were used in medical diagnostics, and Linus Carl Pauling, by discovering the cause of sickle cell anaemia, became, among other things, a co-founder of the science of genetic diseases. Unambiguous proof of the usefulness of chemistry in the field of medical science is also provided by the Nobel Prizes in Chemistry awarded very often for biological objects, the knowledge of which and the determination of how they function are even more important for medicine than for chemistry itself. Sometimes technologies developed by chemists are used for innovative solutions in medicine too.

How?

Such an example is the recent Nobel Prize in Chemistry, which was awarded to Carolyn Bertozzi, Morten Meldal and Barry Sharpless for the development of 'click chemistry' and bioorthogonal chemistry technologies, which will hopefully in the near future find widespread use in pharmaceuticals and medicine to develop anti-cancer drugs that ideally target cancer cells. This is because the key to understanding the complexity of how nature and living organisms function is to learn precisely the chemical nature and structure of the compounds responsible for biological effects, which then brings tangible benefits in the form, for example, of progress being made in developing new, effective treatment therapies. And what should we learn if we want to carry out research in chemistry for biology and medicine? First and foremost, we should keep current research problems and the state of the art in the field side by side in order to design compounds and technologies that are useful for new therapies. We should also work alongside scientists from other disciplines in this area.

Lipids, phospholipids, nanoparticles, biomolecules – when did chemistry stop being about the Periodic Table, simple reactions and counting molar mass?

Everything relevant to this matter started when I completed my PhD thesis. What has defined my research from the start of my PhD till now, concerns the chemistry of natural products. During my PhD, I followed the metabolic pathways of isoprenoid compounds and obtained their bioactive derivatives through biocatalysis with microorganisms, mainly filamentous fungi and yeast. At the postdoctoral research stage, I focused on chemoenzymatic modifications of natural compounds from the damascones and jasmonates group, aiming at the development of a new generation of environmentally friendly biopesticides selectively reducing populations of harmful insect species and formulations effective in the prevention and treatment of cancer, based on the use of terpenoid compounds. After my habilitation, phospholipids became the focus of my research interests, in particular the possibilities they offer for developing methods aimed at improving the pharmacodynamics and pharmacokinetics of polyphenolic compounds as food ingredients.

Polyphenols are a recent discovery. Naturally occurring in most fruits, they have an antioxidant effect and therefore neutralise free radicals. Today, we know that they are one of the factors responsible for inhibiting the body's ageing processes and degenerative changes leading to cancer, among other things.

Food chemistry, in its broadest sense, also influences the formation of proper eating habits, and its importance for the development of the functional food, nutraceuticals and dietary supplements sector is simply crucial.

At the same time, we’re not able to take full advantage of the health-promoting and therapeutic properties of polyphenols found in food. The main limitation when getting them from natural sources is their low bioavailability – at only a few per cent. This is a result of the form in which polyphenols are found in foods. They are bound to saccharides, sterols, polyamines, glycoproteins and lignins that make up cell walls. It would appear that supplementation in free form could be a good solution, but even this does not have the desired effect due to the speed of the metabolism of polyphenolic compounds after their ingestion. The therapeutic effects of polyphenols can only be obtained in very large doses taken over a long period of time.

Eating kilograms of grapes or apple peel every day for a year hoping for their beneficial effects would be difficult.

This is why I have started to develop methods to obtain lipid derivatives of phenylpropanoids – to increase their bioavailability and thus their health-promoting potential in the body. What is also important here is the possibility of extending their industrial application also as natural antioxidants of food products, as their poor solubility in lipid matrices is a limitation. I was therefore engaged in the chemical synthesis of polyphenol-phospholipid hybrid molecules, and after demonstrating their increased anticancer and antidiabetic potential in correlation with their chemical structure. The next step was to optimise the technology for the production of such health-promoting formulas for enhancing food with polyphenolic compounds.

What do we know about phospholipids today?

They are not only components of membrane structures or energy. They are also compounds involved in metabolic and neurological reactions. They regulate basic biological processes and are effective carriers for other biomolecules and drugs. The mechanisms of the phospholipids and the role they play at the molecular level also indicate their high potential in the prevention and treatment of civilisation diseases such as cancer, diabetes or atherosclerosis. However, there is still insufficient knowledge of the receptors and signalling pathways they activate, although these compounds, and especially phosphatidylcholine, which we know by its commercial name lecithin, are widely used in the food, pharmaceutical and cosmetic industries.

Lecithin is probably mainly associated with memory support supplements.

This is true, but phospholipids are used extensively in industry as emulsifiers, stabilisers, viscosity and fluidity regulators, anti-fat-splatter agents during frying or, just mentioned, carriers of biologically active substances. For me, this is just the beginning of my adventure with these compounds. In this scientific adventure, I’m using my experience from working on modifying the structure of phospholipids and my knowledge of the structural dependence of the obtained hybrid molecules on biological activity. Using nanotechnology, I am currently developing nanoformulations of natural biologically active compounds and nanostructured lipid carriers in which clinically used drugs are encapsulated.

Encapsulated, or 'packaged' in a safe carrier?

Yes, because some of them, due to their high toxicity or unwanted side effects, could not be used until now, despite promising results from preliminary studies indicating their chemotherapy-enhancing properties.

Why did you choose chemotherapy in particular? And what is really behind 'food chemistry and biocatalysis'?

I’m a biotechnologist by training, a graduate of our university. And I chose the then Department of Chemistry as the place to do my thesis and chemistry because it is chemistry that underpins every area of human life and activity. It is research in this particular field that has shaped and will continue to shape the world around us, allowing us to understand how it works. Obtaining new biomolecules and discovering the relationships that govern the world at the level of molecules and the reactions between them is simply fascinating. And when it comes to food chemistry, it is a science that deals not only with the composition of food raw materials and final food products. It also studies the behaviour and reactions of food components and the changes that occur in these raw materials and final products under different conditions, that is, during their production, storage or processing.

Is this important?

Of course, because this knowledge is not only used in 'simple' food technology, which is not so simple today. Food chemistry, in its broadest sense, also influences the formation of proper eating habits, and its importance for the development of the functional food, nutraceuticals and dietary supplements sector is simply crucial.

Why?

Because today we look at food more comprehensively. We recognise its additional physiological functions and the impact of its ingredients on the regulation of gene expression. It’s no longer just oatmeal with yoghurt, nuts and grapes, but polyphenols, fibre, unsaturated fats, living colonies of bacteria – in a word, a chemical mini-factory, which affects our body in a specific way, because it provides certain chemical compounds. And today we can modify these compounds to make them even better for us.

In addition to 'food chemistry', we also have 'biocatalysis' in the department name

Biocatalysis is a fundamental tool in the biotechnological process, an important branch of modern organic synthesis, whether in scientific research or in the chemical or pharmaceutical industry. It encompasses processes involving whole microbial cells or isolated enzymes, which are extremely important for the production of specific drugs and active substances, but also for developing methods for degrading of pollutants and the management of waste products. In this area, the Department of Food Chemistry and Biocatalysis and its third head, Professor Antoni Siewinski, have made a huge contribution. Professor Siewinski was a pioneer when it came to biotransformation in Poland. He brought the idea for this type of research to our Department from the Zurich Federal University of Technology (ETH) and developed it with his team despite criticism from the Polish scientific community at the time.

Humility and rebellion are seemingly mutually exclusive, but a scientist should be humbled by the achievements of others, including those of his predecessors, but also have the courage to oppose these achievements in order to pursue his own path of development. What do you think?

Science is unquestionably a process based on the achievements of predecessors, which become the starting point and inspiration for subsequent generations to undertake specific lines of research. This was the case with the aforementioned Professor Siewiński, who started research into biotransformations, and we continue and develop it. I see it, therefore, as a process of adding further bricks to the currently existing state of knowledge, which influences the strong development of a particular trend or, on the contrary, overturns existing theories. The achievements of previous generations in chemistry amaze me with the brilliance of their theses and their high level, especially when we realise that they did not have the analytical tools at their disposal that we use today. At the same time, scientific work teaches humility and patience. The more we know, read, discover, the more humility we have, already realising how much of this knowledge remains to be explored. Humility is also very important, because it breeds vigilance in research and allows us to see what is sometimes a coincidence, and can make a breakthrough on a global scale. This was, after all, the case with Alexander Fleming, the discoverer of penicillin, although with him it is true to say that 'luck favours only industrious minds'. As far as rebellion is concerned, one should break out of established and inappropriate patterns and set new trends.

Who was your mentor?

Good teachers ignite a passion for a particular field of study and research, thus determining to some extent our future. In my case, it was Prof. Czesław Wawrzeńczyk, who got me interested in the chemistry of natural products by identifying isoprenoids as an object of research. He taught me the skills of a scientist. If it were not for him, I would certainly not be where I am today, also in the literal sense – I was looking for an opportunity to do my doctorate in Gdańsk. His knowledge in the field of natural products and organic synthesis that he shared, his support and conversations with Prof. Wawrzeńczyk made it possible for me to be independent after defending my doctoral thesis. In terms of my scientific development and approach to research, I also owe a lot to Prof. Peter Brodelius, whom I joined as a postdoctoral trainee. Working in his team gave me a completely different perspective on research and how to run a team. He hired me for the grant because of my ability to synthesise the products he needed for his research, but I later worked with him on projects to elucidate cell-level mechanisms in plants. This is further proof that we can't move on without chemistry. I must admit that the lessons learned during this period became very valuable to me.  

Not long ago, you were voted best teacher in student surveys. How do you work for such an assessment?

I don't think about surveys. I focus on the substance, i.e. diligently performing the task I was trusted with, which is to impart knowledge as clearly as possible, being fair and demanding. I realise that as a teacher I’m imparting knowledge and many important values to students for their success in their professional life. In classes and lectures, I try to make them think, ask questions and search for answers. The greatest reward for me is to see the effects of my work – when I start to see interest in what I teach, and this interest "explodes" with discussions after lectures. And on the topic of surveys, from my point of view they should be structured differently.

Biotechnology has made breakthroughs in disease research, diagnosis and treatment. Without it, tests for HIV or HCV, for example, would not have been developed. It has made it possible to produce active substances such as cytokines, hormones, monoclonal antibodies or vaccines

How so?

They should give lecturers information on how they can improve. Points do not give such information. Instead of knowing what point range we are operating in, it would be better to find out what we can improve to get maximum marks.  

What do you think academic teaching should be like? What’s the challenge and what is a burden?

In the case of natural sciences, it should give a strong foundation of knowledge in the field and then develop in a given direction in connection with what is currently happening in both the scientific and economic fields. In an environment of ever easier and wider access to knowledge, the challenge is to teach attractively, as it is attractiveness that often determines whether students want to attend lectures and get something out of them, rather than struggling to hide their boredom. When a student has access to basic knowledge, it is the teacher's job to help them organise, explain and consolidate this knowledge. But the teacher must also be an expert who is well versed in the latest scientific issues. Thus, the roles of the research scientist and the teaching scientist teaching specialised subjects intermingle and complement each other. You cannot educate in the latest trends without doing research on them.

You recently won the competition to head the Department of Food Chemistry and Biocatalysis. Is it possible to reconcile management with scientific work, and how?

I am the sixth head of the department and the first woman to hold this position since the department was established in 1952. My predecessors have perfectly demonstrated that it is possible to reconcile management and scientific work very well. Although I will admit that the times and the way of both management and research have changed dramatically in recent years, especially in terms of the pace of change. I think that all current managers would support me in saying that today, in order to reliably fulfil one's organisational and administrative tasks and carry out work in the laboratory, one has to be very well organised and operate on a multi-track level. In terms of management, this is an extremely responsible task that requires a lot of strength and patience. And when it comes to scientific work, when the passion for it is there, it continues to be all about the science.

You are a member of the Leading Research Group Biotechnology for Life and Industry. What is the former and what is the latter?

I have the pleasure of being a member of the Leading Research Group led by Prof Zbigniew Lazar. Working in an interdisciplinary team such as ours is extremely powerful in stimulating development, creativity and raising the level of discussion and research. Although we each work in our own area and carry out our own research, combining them brings a new quality for the benefit of creating biotechnological solutions. In the aspect of biotechnology for life, we are concerned with bioactive food ingredients, the search for biotechnological methods for their production, the modification of microorganisms and plants to meet production needs, the modification of food ingredients at the molecular level, the search for efficient delivery systems, the utilisation of contaminants and waste products from the agri-food industry. The proposed technologies and solutions, on the other hand, are intended to serve industry, to be attractive and innovative for it.

Is biotechnology changing the modern world?

Definitely, and these changes have already taken place. In the face of the crises that threaten us, such as securing food resources, maintaining the health of ageing populations, and the availability of safe sources of energy and raw materials, biotechnology is crucial. Its most significant element was the launch of the Human Genome Project (HGP) in the USA in 1990. Biotechnology has made breakthroughs in disease research, diagnosis and treatment. Without it, tests for HIV or HCV, for example, would not have been developed. It has made it possible to produce active substances such as cytokines, hormones, monoclonal antibodies or vaccines. In this respect, we also have Polish successes to our credit. One of them is the launch of industrial-scale production of recombinant human insulin in 2000. So we can safely say that the efforts of biotechnologists are aimed at improving our lives and making the industry able to create products that are best suited to us and our needs from both a nutritional and a therapeutic point of view.

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