Featured Lendület Member: Lilla Turiák
Membrane proteins sitting on the surface of tumour cells are often associated with sugar side chains, which have a significant impact on the function of the protein and the entire cell. In many cases, for example, these side chains determine whether or not a drug molecule enters the cell. Therefore, by examining these features, it is possible to predict how successful different therapies may be for a particular patient. Lilla Turiák, Senior Research Fellow at the Institute of Organic Chemistry of the HUN-REN Research Centre for Natural Sciences and head of the MTA-TTK Lendület (Momentum) Glycan Biomarker Research Group, and her colleagues are developing methods to study the effect of proteins with a sugar side chain on cancer with support from the Momentum Programme.
Turiák graduated as a pharmacist from Semmelweis University and started working with mass spectrometry during her PhD research at the Central Institute of Chemical Research of the Hungarian Academy of Sciences. This instrumental analytical technique is of paramount importance when components of different complex samples need to be determined qualitatively and quantitatively with high sensitivity. This is particularly important for proteins, since even small amounts of tissue, blood or urine samples can be analysed with high-throughput mass spectrometry. With the latest instruments, thousands of proteins can be determined from a sample.
Lilla TuriákMore detailed information on tumours
Biological conclusions about the course of various diseases can be drawn from the amount of identified proteins, but even new drug targets can be identified and previously unknown biomarkers can be discovered. “I feel fortunate to be able to use the chemical and biological knowledge that comes from my background as a pharmacist, as I work with analytical procedures, but a biological background is also essential to interpret the data,” admits the team leader.
It was during her studies at Boston University that she began to work more deeply with the analysis of sugar chains associated with proteins. Most of the membrane-embedded proteins involved in various cell-level signalling processes are glycosylated, that is contain sugar chains, and play an important role in cell-to-cell communication. For example, viruses enter cells through such cell surface receptors containing sugar chains. “As a postdoctoral researcher in the United States, I started examining very small tissue areas and developed workflows to study not only one class of molecules, but several molecular classes, such as several types of sugars, or the proteins themselves,” continues Turiák. “When I moved back home, I first worked on prostate cancer tissues because I was always interested in cancer research and how to obtain as much detailed information as possible about tumours based on a small amount of samples.”
She applied the work process she had developed to sections containing small tissue biopsies to study the altered proteins and sugar chains in them.
She was looking for changes in proteins that occur during tumour progression and how the process of glycosylation is altered.
She then switched from prostate cancer to lung cancer because patients with lung cancer have poorer survival rates. Lung cancer also has a higher incidence and mortality in Hungary. A particularly big problem is that in many cases the tumour becomes resistant to the given treatment.
Predicting the effectiveness of treatment
“In many cases, patients respond well for a while, but over time they somehow become resistant,” says the researcher. “In this regard, I first examined tissue samples from lung cancer patients who had different mutations. Over the course of the retrospective study, I was looking to find out what changes occur in the proteins and their associated sugars that might be related to whether the patient responds to the therapy. If we manage to understand all this, then it might be possible to predict this.”
Turiák submitted the Momentum application to take this further. The main goal is to predict whether a patient will respond well to a therapy in the long term by characterising the glycosylation of extracellular vesicles isolated from blood (i.e. by taking a simple blood sample). The researcher had already worked on the proteomic characterisation of extracellular vesicles during her PhD research in collaboration with Edit Buzás’ research group. These vesicles are membrane-bounded structures that detach from the cell membrane and enter the intercellular space, carrying with them various components of the original tumour cell, including some membrane proteins. This line of research has become very popular in the last 15 years, as it has been shown that these vesicles play an important role in intercellular communication. There are many proteomic, lipidomic and transcriptomic studies taking place on them, but according to Turiák, the post-translational modifications of the membrane proteins embedded in their membranes, such as the sugar chains associated with them, have been characterised by few researchers.
This is because this study is analytically challenging, partly due to the small sample size.
“The ultimate aim of the project is to isolate circulating tumour-derived vesicles from the plasma of lung tumour patients and to characterise the sugar chains associated with the proteins they contain using modern bioanalytical tools such as mass spectrometry,”
says Turiák. “Many steps in the development of the methodology will need to be optimised. A major problem is, for example, that the plasma does not only contain vesicles secreted by the tumour, as almost all cells release similar membrane spheres. So tumour-derived vesicles need to be selectively enriched so that we only examine what is associated with the disease.”
Immunoaffinity-based capture methods will be optimised for selective enrichment. As part of a prospective study, blood will be taken from newly diagnosed lung tumour patients, and this will be repeated every three months during immunotherapy. Clinical parameters indicative of patients’ responses to treatment will be monitored over time and compared with changes in protein sugar chains. They hope to find characteristics that will predict who will respond well to a given treatment and who will not.
Sugar side chains can bind different proteins and, depending on their structure, play a role in signalling pathways. For example, in the case of Covid’s pathogen, the glycosylation of the coronavirus spike protein dictates that it can bind to the angiotensin-converting enzyme receptor and thus enter the cell. “In the case of tumour cells, the big question is what exactly is the biological basis for the changes in the sugar side chains. It is certain that certain protein bonds in the tumour microenvironment are altered,” the researcher says. “When these vesicles are released, for example, during metastasis, they transmit information to the surrounding cells, thus stimulating malignant cell proliferation. But the role of these sugar side chains in drug resistance has also been described: if glycosylation on the surface changes, the cell can no longer take up the drug molecule it is trying to attack.”
A témához kapcsolódó cikkeink
Featured Lendület Member: Miklós Sebők
In the last decades, there have been significant changes in the foreign policy orientation of the Visegrád countries: the unilateral Euro-Atlantic orientation has been replaced by an East-West mixed orientation. Miklós Sebők, Research Professor at the HUN-REN Centre for Social Sciences, Institute of Political Science, Department for Government and Public Policy, and head of the MTA-TK Lendület (Momentum) V-SHIFT Research Group, and his colleagues use state-of-the-art artificial intelligence methods to investigate the foreign policy shifts in the countries of the Central and Eastern European region, based on all parliamentary documents and countless newspaper articles of the past 35 years. Such a scale and depth of analysis would have been unthinkable before AI.
Featured Lendület Member: Gergely Róna
Errors in the DNA sequence occur regularly and need to be corrected immediately to maintain normal gene function. DNA repair mechanisms associated with DNA replication are well known, but DNA error repair also occurs in non-dividing cells, about which much less is known. However, many diseases, such as some neurodegenerative diseases, are caused by DNA errors in non-dividing cells. Gergely Róna, head of the MTA-TTK Lendület (Momentum) DNA Error Repair Research Group and researcher at the Institute of Molecular Life Sciences of the HUN-REN Research Centre for Natural Sciences, and his colleagues are investigating little-known forms of DNA repair mechanisms with the support of the Momentum Programme.
Featured Lendület Researcher: Szimonetta Lohner
In medical research, it is vitally important that each study is conducted in accordance with international professional recommendations and expectations, that the results are accessible to all, and that the lessons of proven discoveries are transferred into clinical practice as soon as possible. However, these conditions are not always met. Szimonetta Lohner, Associate Professor at the Institute of Public Health Medicine at the University of Pécs, and her research group, established under the Momentum Programme, is investigating the practice of medical research to achieve these goals.
Featured Lendület Researcher: Maria Lugaro
Maria Lugaro investigates the circumstances of the birth of stars and planets with the support of MTA’s Lendület (Momentum) Programme. To this end, the astronomer and her colleagues will analyse data obtained by testing stardust in the laboratory.
Featured Lendület Member: Peter Maga
Automorphic forms are among the most interesting objects of mathematical research today, since they serve as a link between many subfields of mathematics, such as number theory and partial differential equations. Peter Maga, Senior Research Fellow at the HUN-REN Alfréd Rényi Institute of Mathematics, and his Momentum research group will be investigating automorphic forms on higher-rank groups in the coming years.
Featured Lendület Researcher: Zoltán Novák
The chemical and pharmaceutical industries would be unthinkable today without catalysts. Therefore, the development of increasingly efficient catalysts is one of the most important goals of chemistry, as these catalysts make chemical synthesis cheaper, more sustainable and environmentally friendly. Zoltán Novák, professor in the Department of Organic Chemistry at ELTE and head of the Sustainable Catalytic Processes Research Group, and his colleagues are also working on the development of new types of catalysts which are partially recyclable and reusable and require only small amounts, can be activated by controllable external impulses, and do not require expensive precious metals.
Featured Lendület Member: László Acsády
The thalamus is one of the most underestimated brain areas. According to the classical view, its only job is to act as a switching station between the cerebral cortex and stimuli from the outside world. However, László Acsády, head of the MTA-KOKI Momentum Thalamus Research Group and deputy director of the HUN-REN Institute of Experimental Medicine (KOKI), and his colleagues have shown in recent decades that this view could not be further from the truth. Indeed, the complex communication between the cortex and the thalamus and the processing that takes place in the thalamic cells prove that this brain area plays an active role in brain function. His brain research team can now continue their research with funding from the Momentum Programme.
Featured Lendület Member: András Abonyi
Riverine plankton communities are of crucial importance in maintaining the ecological health of rivers, yet compared to standing water plankton, the community of riverine floating organisms is very poorly studied. András Abonyi, Senior Research Fellow at the Institute of Aquatic Ecology of the Centre for Ecological Research, is changing this. He is the head of the Momentum Research Group on River Ecology and, with the support of the Momentum Programme, is investigating the transformation of the plankton community in rivers in response to river regulation and changes over time.
Featured Lendület Member: András Attila Horváth
A growing body of research suggests that there is a link between epilepsy-related cortical hyperexcitability (i.e. excessive neuronal activity) and pathologies associated with cognitive decline, such as dementia. András Attila Horváth, Director of the Neurocognitive Research Centre of the National Institute of Mental Health, Neurology and Neurosurgery and head of the MTA-OMIII Lendület (Momentum) Neurocognitive Research Group, and his colleagues are trying to uncover the mechanism underlying this relationship. Their results could lead to new targets for treatment.
Featured Lendület Member: Gábor Juhász
The healthy functioning of cells is inconceivable without the digestion and breakdown of defective or redundant materials or substances that have been absorbed. If this system does not function properly, it can have a number of pathological consequences. These cellular breakdown processes are carried out by membrane-lined vesicles called lysosomes. They are investigated by Gábor Juhász, Scientific Advisor of the Institute of Genetics at the Szeged Biological Research Centre and Head of the Lysosomal Degradation Research Group, with the support of the Hungarian Academy of Sciences’ Lendület Programme.
Featured Lendület Member: Viktória Kiss
In the Bronze Age in the Carpathian Basin, huge social changes took place in the population living in the territory of present-day Hungary. Viktória Kiss, Senior Research Fellow at the Institute of Archaeology of the HUN-REN Research Centre for the Humanities and head of the MTA-BTK Lendület (Momentum) Base Research Group, and her colleagues are investigating these processes and the characteristics of the people who lived there. They are using state-of-the-art computer science, genetic and isotope-geochemical methods for this work.
Featured Lendület Member: Ildikó Király
In our conversations, we often recall memories which did not really happen, but are just a figment of our imagination, yet tell them enthusiastically, with full feeling, to our interlocutors. They are not lies, because we believe that they really happened to us. Ildikó Király, professor, Head of the Department of Cognitive Psychology at ELTE and Head of the Lendület MTA-ELTE Research Group on Social Minds, and her colleagues will be researching the formation, functioning and adaptive role of these memories in the coming years. These constructed memories seem to play an important role in our social relationships.
Featured Lendület Member: Ádám Gali
Quantum technology has the potential to revolutionise many branches of electronics, from communication to sensors to computing. Ádám Gali, professor, advisor to the Institute of Solid State Physics and Optics at the Wigner Research Centre for Physics, and head of the Lendület-funded Semiconductor Nanostructures Research Group, has been researching quantum bits in solids for some time. Since last year, he has continued his research as a winner of the now-advanced Lendület grant. Based on his results, he and his fellow researchers can lay the foundations for new types of quantum sensors.
Featured Lendület Member: Imre Norbert Orbulov
Composite metal foams have played a significant role in many areas of industry over the last decades (for example, they are used in impact and blast protection of buildings and vehicles), but the methods used to develop them are now becoming less and less viable. Imre Norbert Orbulov, Dean of the Faculty of Mechanical Engineering at the Budapest University of Technology and Economics (BME), Professor of Materials Science and Technology, and head of the MTA-BME Research Group on High Performance Composite Metal Foams, and his colleagues are therefore exploring radically new approaches to the development of metal foams to help develop materials with significantly improved properties.
Featured Lendület Member: Emőke Rita Szilágyi
Most people know only a few significant Hungarian humanist authors from the 15th and 17th centuries (the most famous of them being Janus Pannonius, Balassi and Zrínyi), although many other writers and poets also worked in Hungary during this period. Emőke Rita Szilágyi, research fellow at the Institute of Literary Studies at Research Centre for Humanities, head of the Lendület research group on Humanist Canons and Identities in the Kingdom of Hungary (1450-1630), is trying to remedy this shortcoming with her winning Lendület grant: in the coming years, she will investigate who among the authors active in the 15th through 17th centuries have remained in the public consciousness, and why, or why they have fallen out of it.
Featured Lendület Member: Anna Szécsényi-Nagy
Although there are many written sources on the Roman period, very little is known about the biological, medical, nutritional and many other characteristics of the population of Pannonia. This will be remedied by the research of Anna Szécsényi-Nagy, archaeogeneticist, archaeologist, senior research fellow at the Institute of Archaeogenomics of the HUN-REN Research Centre for the Humanities, head of the MTA-BTK Lendület Bioarchaeology Research Group, and her colleagues, who will also study, for example, camels brought here by the Romans.
Featured Lendület Member: Zsuzsanna Kolbert Ördögné
In the near future, agriculture will have to face increasingly severe droughts, so we need to increase productivity in the face of growing stress to provide food for an ever-increasing human population. Zsuzsanna Kolbert Ördögné, Associate Professor at the Department of Plant Biology, University of Szeged and head of the Lendület Plant Nanobiology Research Group, and her colleagues are investigating what role seed priming with nanoagents can play in improving drought tolerance in cultivated plants.
Featured Lendület Member: Andrea Toldy
How can waste from cross-linked polymers, which make up a smaller proportion of plastics, be recycled? Andrea Toldy, Professor in the Department of Polymer Engineering at the Budapest University of Technology and Economics, and head of the MTA-BME Lendület Sustainable Polymers Research Group, is seeking answers to this question with the support of MTA’s Lendület Programme.