News

Wednesday, August 30, 2017

Academy of Finland awarded Tapio Lönnberg (Finnish Functional Genomics Centre) with Academy Postdoctoral Fellow funding 280 000 € for 2017-2020

 

Academy of Finland awarded Tapio Lönnberg (Finnish Functional Genomics Centre) with Academy Postdoctoral Fellow funding 280 000 € for 2017-2020

 

Single-cell Atlas of human follicular T helper cells in Health and Disease

Generation of protective antibodies results from collaboration of two types of cells: B-cells and Follicular T helper cells (Tfh cells). Tfh cells can be further divided into several subsets, some of which are associated with autoimmune disorders. However, the full extent and functional implications of this subset diversity remain incompletely understood. To date, Tfh cells have been difficult to study in human due to their diversity and localization in lymph nodes.

We are exploiting novel methods enabling the determination of functional states of single cells by measuring gene expression. This allows us to target those rare Tfh cells, which have migrated from lymph nodes to peripheral blood, and are therefore accessible to sampling. By comparing cells from healthy volunteers and Rheumatoid Arthritis patients, we aim to identify disease-associated subsets of cells, providing new targets for therapeutic interventions.

Friday, June 9, 2017

Academy of Finland awarded Guillaume Jacquemet (Ivaska lab) with Academy Postdoctoral Fellow funding 259 054 € for 2017-2020

 

Academy of Finland awarded Guillaume Jacquemet (Ivaska lab) with Academy Postdoctoral Fellow funding 259 054 € for 2017-2020

Myo10 filopodia and cancer metastasis
The formation of metastases is responsible for 90% of deaths in patients with solid tumours. Consequently, there is a pressing need to develop therapeutic strategies that block the ability of cancer cell to disseminate throughout the body. We and others have made an intriguing discovery that cancer metastasis is associated with the development of specialized cellular protrusions called filopodia. In migrating cells, filopodia are “antenna-like” protrusions, which contain cell-surface adhesion receptors, such as integrins, responsible for constantly probing the cellular environment. At filopodia, integrins modulate signalling pathways that support cell migration, survival and proliferation. Integrins are transported to filopodia via a motor protein called Myosin-X, a regulator of filopodia formation. Based on our breakthrough experiments, we discovered that myosin-X contribute to cancer cell metastases in vitro and in vivo models and that myosin-X is highly expressed in patient samples (including breast, pancreatic, colorectal, glioma and lung carcinoma) where it correlates with poor prognosis. These results clearly indicate that myosin-X is a promising novel target for anti-cancer therapies. Data I accumulated to date clearly demonstrate that myosin-X-mediated transport of integrins, together with integrin signalling in filopodia are two important prerequisites for cancer metastasis. Therefore, I aim to develop strategies to target myosin-X in cancer by 1) generating myosin-X-specific small molecule inhibitors in collaboration with the non-profit organization CD3 (University of Leuven), 2) identifying the regulatory mechanisms by which myosin-X transports integrins to filopodia and 3) assessing the role of Myo10 filopodia in in vivo dissemination of cancer cells using intravital microscopy. If sucessful, our findings will lead to the development of a drug that can inhibit Myo10 function in cancer and thus provide novel and desperately needed therapeutic strategies for treating metastatic pancreatic and breast cancer as well as other cancer forms.

Friday, June 2, 2017

Academy of Finland awarded Maria Georgiadou (Ivaska lab) with Academy Postdoctoral Fellow funding 261 109 € for 2017-2020

 

Academy of Finland awarded Maria Georgiadou (Ivaska lab) with Academy Postdoctoral Fellow funding 261 109 € for 2017-2020

Project title: Cell metabolism and Tyrosine phosphorylation as novel regulators of integrin activity.

Project description: Integrins are cell adhesion receptors playing essential roles in health and disease, by regulating cell migration, survival, proliferation, differentiation. Integrins are expressed at the plasma membrane both in a low-affinity “inactive” state and in a high-affinity “active” state. Integrin activation leads to enhanced signalling and inappropriate integrin activation has been linked to several diseases, including cancer. Hence, understanding how integrin activity is regulated is of major clinical relevance. In an effort to identify novel integrin activity regulators Johanna Ivaska’s laboratory (host laboratory) has performed RNAi screens in several cancer cell lines. In those screens the metabolic sensor AMP-kinase (AMPK) and many other genes involved in metabolism were identified as potential regulators of integrin activity. The aims of the project are twofold: (1) to identify the cellular signalling pathways involved in ?1-integrin tyrosine phosphorylation and their role in integrin activity and matrix formation in fibroblasts; and (2) to characterize the role of metabolism in regulating integrin activity, migration and invasion in cancer cells.

Tuesday, May 30, 2017

Researchers invented a tools to decode and control signalling circuits in living cells with flashes of light

 

Researchers at the Turku Centre for Biotechnology have invented new tools to decode and control signalling circuits in living cells with flashes of light. In principle, any cellular circuit can now be targeted with their method. Using this approach, they discovered that major biological signalling circuits can be made to resonate when driven at their resonant frequency.

Resonance is a familiar concept in music, physics and engineering and underlies technical approaches in chemistry, biology and medicine.
– Our discovery that signalling circuits of mammalian cells can made to resonate, is new and is likely to have relevance to disease. With this information we may control, when the signalling pathway is on or off, senior researcher Michael Courtney from Turku Centre for Biotechnology says.

The team developed optogenetic inhibitors of protein kinases such as JNK, a central regulator of cell function.
– JNK protein in the cell cytoplasm was not thought to regulate gene expression in the nucleus and continuous inhibition in the cytoplasm is ineffective. However, the team found that delivering a specific frequency of inhibition pulses to JNK in the cytoplasm drove inhibition of gene expression in the nucleus. This indicates that cell signalling circuits can be controlled in previously unforeseen ways once the appropriate time-code has been identified, Courtney says.

He explains that not only might cell circuit resonance play an unexpected role in degenerative disease processes, but it could even guide the discovery of new therapeutic approaches. Interestingly, the only previous report on cell circuit resonance in the scientific literature showed it can be used to prevent microbial cells from growing. The new finding of similar behaviour in mammals suggests it could potentially be used to stop cancer cells growing.

– Currently, the development of resistance to new drugs is a major problem in cancer, as new drugs cost billions of dollars to develop and approve and yet they can rapidly become ineffective in patients. With new research, we can perhaps consider to change the frequency of inhibition instead of using the same drug continuously, and in this way, achieve a better outcome, Courtney says.

The Turku team’s newly discovered phenomenon of circuit resonance in mammalian cells might offer a way to avoid or work around drug resistance. The researchers have now assembled a research consortium which has applied for funding to begin the evaluation of this idea.
The team started developing the light-regulated tools while at the University of Eastern Finland funded primarily by the Academy of Finland Photonics programme. The mammalian circuit resonance was discovered and characterised by the team after moving to the University of Turku, with support from the Turku Bioimaging Screening Unit and grants from the National Cancer Institute in US, the EU-Marie Sk?odowska Curie programme and Finnish foundations including the Magnus Ehrnrooth, Alfred Kordelin, Instrumentarium and Orion Foundations.

This work was published in the journal Nature Communications on the 12th of May 2017.
Original publication: Melero-Fernandez de Mera RM1, Li LL1, Popinigis A, Cisek K, Tuittila M, Yadav L, Serva A, Courtney MJ (2017) A simple optogenetic MAPK inhibitor design reveals resonance between transcription-regulating circuitry and temporally-encoded inputs. 1equal contribution. Nat. Commun. 8, 15017 doi: 10.1038/ncomms15017.
Read the article: https://www.nature.com/articles/ncomms15017

More information: Senior Researcher Michael Courtney, University of Turku, Turku Centre for Biotechnology, tel. +358 (0)504649827 , e-mail miccou@utu.fi

Tuesday, May 23, 2017

Academy of Finland awarded Laura Elo with Academy Research Fellow funding 434 500 € for 2017-2022

 

Project title: Tools to translate proteomes to human health and diagnostics

Development of robust, versatile and easy-to-use computational tools is crucial to translate the emerging proteome data to patient benefits. Despite advances in proteomics measurement technologies, a common problem in most protein biomarker studies remains that the findings cannot be validated in new studies. This project addresses this challenge by developing a robust computational framework for proteome data that uses longitudinal follow-up data over time and is widely applicable on different types of proteome data, including the emerging fields of single cell proteomics and metaproteomics. By combining multidisciplinary expertise in statistical and machine learning methods, proteomics technologies and clinical research, the project is anticipated to accelerate the development of improved diagnosis, prognosis and treatment strategies for complex diseases, such as diabetes and cardiovascular diseases. The computational framework will be useful in a wide range of medical applications.

Thursday, May 18, 2017

Adaptive Clinical Trials - A new concept to improve and accelerate the clinical testing of cancer drugs in Finland

 

A joint development project by University of Helsinki and University of Turku has been awarded with over 2 million Euros in the Challenge Finland competition. The project is called TEHO adaptive clinical trial design – poised to accelerate approval.

The goal of this 2-year project is to advance the Finnish drug discovery research and its innovations by developing a new concept of adaptive clinical trials. Finland is home to numerous innovations in oncology and cancer therapeutics. However, only a few of these innovations currently reach clinical practice where they would benefit cancer patients. The TEHO project aims to develop a new, faster and more efficient, adaptive approach to clinical trials which constitute one major bottleneck in transforming Finnish innovations in cancer research into new, effective therapeutics.

The TEHO project will approach this challenge by developing and validating new multifaceted approach to clinical testing. Our aim is to utilize latest data from preclinical cancer models, predictive biomarkers and computational simulations parallel to an active clinical trial. This new adaptive concept will make it possible to evaluate the clinical significance of the proposed markers of clinical efficacy before and during the actual clinical testing. Therefore, this new paradigm will dramatically decrease the time and cost of clinical testing and accelerate clinical adoption of new cancer therapeutics since it will be possible to make evidence-based real-time adjustments to patient cohorts and drug doses throughout the trial.

TEHO project comprehensively combines various aspects of Finnish preclinical and clinical research. Upon completion, the TEHO project will provide new opportunities for commercial utilization of Finnish translational oncology research and benefit both the Finnish drug discovery ecosystem and cancer patients worldwide.

TEHO is a collaborative partnership between academia and industry, whose members include University of Helsinki, University of Turku, Comprehensive Cancer Center, AbbVie Oy, Aurexel Life Sciences Ltd, Bayer Oy, Biomedicum Genomics Oy, Orion Oyj, PacoMed Oy and StatFinn Oy. Responsible project directors are the cancer scientists Juha Klefström from the University of Helsinki and Jukka Westermarck from the University of Turku.

Background on Challenge Finland competition
Challenge Finland competition by Tekes is an embodiment of the goals set by the current government to foster national expertise and education. The goal of Challenge Finland program is to uncover commercially viable solutions to significant needs by combining Finnish knowledge and innovations with research and development of Finland-based companies. In the spring of 2016 Tekes selected 70 most promising project proposals from nearly 300 applications. These finalists were then given the opportunity to further develop their original concept and identify industrial partners for eventual commercialization. The best projects were subsequently awarded funding for the years 2017 and 2018.

Additional information will be provided by Juha Klefström (juha.klefstrom@helsinki.fi, tel. 044-377 3876) and Jukka Westermarck (jukka.westermarck@utu.fi, tel. 040-742 3007).

Thursday, May 4, 2017

Academy of Finland awarded Eleanor Coffey with 400 000 € project funding

 

Validation of a new therapeutic avenue for the treatment of depression and anxiety

Depression and anxiety are a significant cause of disability globally. Treatment resistant depression and comorbid anxiety account for 50% of sufferers. Lack of effective treatments indicates that the etiology of depression is incompletely understood. These disorders result from circuit level maladaptation involving multiple brain regions. Our lab has shown that JNK modulates anxiety in mice and that JNK inhibition in a subset of cells in hippocampus alleviates anxiety.

This project will test the usefulness of cell-specific JNK inhibition for clinical depression using early life stress models. We will use fiber photometry to precisely define how JNK alters neural connectivity to control mood. Single cell transcriptomics will define JNK-regulated genes that confer susceptibility to anxiety and depression. This will establish the validity of targeting JNK as a new therapeutic avenue for treatment resistant depression and anxiety, while gaining insight on the underlying mechanism.

Thursday, May 4, 2017

Jukka Westermarck elected to Finnish Academy of Science and Letters

 

Jukka Westermarck, Research Professor of the Finnish Cancer Institute at Turku Centre for Biotechnology, has been elected as new member of the Finnish Academy of Science and Letters together with University of Turku Academy Professor of cultural history Hannu Salmi.

At the annual meeting, the Finnish Academy of Science and Letters appointed a total of 27 new scientists in Finland as members of the Mathematics and Natural Sciences and Humanities department. 11 foreign members were elected at the same meeting.

The principal aim of Finnish Academy of Science and Letters is to promote scientific research and to act as a bond between those engaged in advanced research.

Finnish Academy of Science and Letters

Wednesday, March 29, 2017

Scientific Discovery Opens New Possibilities for Cancer and Fibrosis Treatment

 

Researchers from the Turku Centre for Biotechnology (BTK) in Finland have discovered that a cellular fuel sensor, known to control energy processes in the cells, is involved in the regulation of the contact of cells with their surrounding environment. This unexpected link could help scientists better understand life-threatening diseases, such as cancer and tissue fibrosis.

The researchers found that a cellular fuel sensor called AMPK controls integrin function and the production of extracellular matrix.
– This is a significant finding, since the rather cheap and widely-used drug called metformin activates the AMPK sensor in particular and inhibits diabetes, cancer, fibrosis and cardiovascular diseases, and promotes longevity. Our discovery opens up new therapeutic opportunities for the treatment of these diseases, says Academy Professor Johanna Ivaska, senior author of the study.

The space between the cells of human tissues is filled with a meshwork of different proteins called the extracellular matrix. The cells are connected with the extracellular matrix through protein complexes called adhesions. The main proteins in those adhesions are the integrins which link the cytoskeleton with its environment. The researchers have found that in the absence of the fuel sensor AMPK, fibroblasts activate their integrins increasing their adhesion and matrix production. This increase is attributed to a protein called tensin.

– AMPK is known to control energy homeostasis. In our study, we have shown that this fuel sensor can also regulate integrin signaling and matrix formation, suggesting that AMPK serves as a general master switch in our body. Our aim was to identify potential novel targets to treat diseases associated with excessive matrix formation, such as cancer and fibrotic diseases which are major causes of morbidity and mortality worldwide, reports Maria Georgiadou, first author of the work.

The findings were published in the internationally renowned Journal of Cell Biology on 13 March 2017.
Original publication: AMPK negatively regulates tensin-dependent integrin activity. Maria Georgiadou, Johanna Lilja, Guillaume Jacquemet, Camilo Guzmán, Maria Rafaeva, Charlotte Alibert, Yan Yan, Pranshu Sahgal, Martina Lerche, Jean-Baptiste Manneville, Tomi P. Mäkelä and Johanna Ivaska. DOI: 10.1083/jcb.201609066 | Published 13 March 2017.

For more information:  

University of Turku / Turku Centre for Biotechnology
Academy Professor Johanna Ivaska
tel. +358 40 50 20 812, johanna.ivaska@utu.fi

Tuesday, March 14, 2017

The researchers from Turku Centre for Biotechnology discovered an unexpected link between cancer and autism

 

The novel discovery impinges upon the protein called SHANK which has been intensively studied in several processes in central nervous system and gene mutations in SHANK are linked to autism.

Large-scale screens aiming at find potential new genes regulating cancer cell metastasis revealed to the research team an unexpected link between brain development and tumor invasion.

“Amazingly, the ability of cancer cells to adhere and migrate on their environment and invade into surrounding tissue were prevented by SHANK protein – a molecule previously studied in the central nervous system and linked to autism. “, describes graduate student Johanna Lilja.

In cell culture experiments, the researchers found that SHANK protein limits the ability of a protein called Rap1 to activate cell adhesion receptors, integrins. This same mechanism regulated cancer cell motility as well as the morphology and branching of neurites, known to be essential for normal brain function.

To reveal the underlying mechanism the co-operation of three international research group was needed. Dr. Igor Barsukov’s laboratory from University of Liverpool solved the 3-dimensional structure of SHANK protein, which led the researchers to study the correct mechanism. Then, Ivaska’s research team in collaboration with neuroscientist Dr. Hans-Juergen Kreienkamp from Institute for Human Genetics, Hamburg, studied the function of SHANK in both cancer cells and neurons.

“The same factors can regulate cell shape and adhesion in very different cell types. Our results revealed that gene mutations in SHANK, found in autistic patients, impair SHANKs ability to prevent the adherence of both neurons and breast cancer cells. This once again demonstrates the power of basic research in facilitating our understanding of several human diseases”, rejoices Academy professor Johanna Ivaska.

Ivaska’s research team is working at Turku Centre for Biotechnology, University of Turku and Åbo Academy.
The research team and their collaborators are currently assessing if SHANK proteins have other impacts on cancer cells – especially on their proliferation.

The findings were published in the highly appreciated Nature Cell Biology – journal on the 6th of March 2017.
Original publication:  SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras. Johanna Lilja, Thomas Zacharchenko, Maria Georgiadou, Guillaume Jacquemet, Nicola De Franceschi, Emilia Peuhu, Hellyeh Hamidi, Jeroen Pouwels, Victoria Martens, Fatemeh Hassani Nia, Malte Beifuss, Tobias Boeckers, Hans-Juergen Kreienkamp, Igor L. Barsukov & Johanna Ivaska. Nature Cell Biology (2017). doi:10.1038/ncb3487; Published online 06 March 2017
For more information:
 
University of Turku / Turku Centre for Biotechnology
Academy Professor Johanna Ivaska
tel. +358 40 50 20 812, johanna.ivaska@utu.fi