Pál Gábor: Irányított fehérjeevolúció alapkutatástól gyógyszerfejlesztésig
László Poppe: Francis Arnold: Revolution based on evolution
József Tímár: The enemy of my enemy is my friend: Medical Nobel prize 2018: Basics of immunoncology
It was a long presistent idea among immunologists that stimulation of the immune system could be the way to achieve antitumoral immune responses. However, these techniques failed to be clinically active. Tumor immunology in the meantime disregarded the fact that negative regulation of the T-cell receptor signaling is equally important compared to stimulatory regulations in T-cell mediated immune responses. Recently than it was discovered that cancers are actively blocking the mounting antitumoral immune responses by activating the so-called check-point inhibitory mechanisms such as CTLA-4 and PD/PDL1.
The role of the scaffold protein Tks4 in cancer cell motility – László Buday, András Czirók
The scaffold protein Tks4 is a participant both in EGFR singalling and podosome formation. Our joint experiments showed, that the functional deletion of Tks4 (Tks4 KO) alters the motility of human colorectal carcinome cells. The Tks4 KO cells are able to make longer journeys and do them faster, than their wild type counterparts.
Setup of inflammation induced permeability measurements by gold nanoparticles and optical biosensor – László Cervenak , István László Lagzi, Róbert Horváth
We investigated and monitored the penetration of charged nanoparticles into adhered HeLa cells by using Epic BT optical biosensor in a real-time and completely label-free manner. Our results show that the cellular uptake of positively charged nanoparticles (AuTMA) is more effective compared to the negatively charged nanoparticles (citrate capped nanoparticles). This finding supports our hypothesis that the cell membrane and nanoparticle interaction plays a crucial role in the penetration of the charged particles since the membrane composition of the cells are negatively charged, thus attractive electrostatic interaction can help nanoparticles to be internalized into the cells.
Podocin: the pivotal relationship of the transmission rate and the oligomerization of a membrane protein – Dóra K.Menyhárd, Gusztáv Schay, Kálmán Tory
Podocin is the first protein with an oligomerization-dependent variant (R229Q), which is only pathogenic in specific heterooligomers. During the last years, we revealed several aspects of the underlying pathomechanism: the oligomerization sites, the effect of R229Q on the oligomerization and its relationship with the membrane-targeting. Such a mutation-dependent pathogenicity of a variant is a challenging aspect in the clinical practice: to help its assessment we recently set up population-genetic, biochemical and clinical criteria.
Mastering Cell Counting: about the Countess FL instrument – Szilvia Bősze, Tamás Beke-Somfai
The Countess™ II FL Automated Cell Counter is a benchtop assay platform equipped with state-of-the-art optics for rapid assessment of cells in suspension. With three-channel flexibility — brightfield and two optional fluorescence channels— cell viability, cell size distribution can be measured. The cytotoxicity, apoptotic or proliferative effect of different antimicrobial and antitumor peptides, foldamers and their derivatives can be determined in a high-throughput manner exhibiting plate-based assay quality.
Inhibition of pathophysiological interactions of S100 proteins with foldamers - László Nyitray, Tamás Martinek
The aim of the cooperation is to find high affinity foldameric ligands of S100 proteins to disrupt their pathophysiological protein-protein interactions.
First, to find low micromolar binding partners, the surfaces of 8 members of the S100 protein family were mapped with a 256-membered foldamer helix library using a pulldown-assay, then fluorescence polarization was measured to quantify the interactions between selected foldameric fragments and different S100 proteins.
In case of S100A4 and S100B, which are particularly important in therapeutic point of view, competitive pulldown assays were performed to confirm that the recognition site of the foldameric fragments is the same as the native ligands.
Péter Gál: Proteases in the immune system: The complement system
New tricks for an ancient system
The complement system, consisting of exclusively protein molecules, is a powerful effector component of the innate immune system. The system has about 40 protein components and contributes to the development of the immune response in various ways. In the recent years we have discovered novel functions of the complement system ranging from the direct cell activation to the facilitation of the blood coagulation.
Attila Reményi: Protein kinas
Protein kinases rarely act solo, as they are part of hierarchically organized cascades or more intertwined kinase networks. Surprisingly we know little about how kinases get turned on by other kinases because we lack structural information on how kinase heterodimers assemble. In my talk I will present how different MAP kinases specifically turn on other kinases involved in cell growth or death.
András Szarka: The investigation of the key proteins in high dose ascorbate and acetaminophen induced cell death
High dose ascorbate and acetaminophen induced cell death and ferroptosis share common features such as production of reactive oxygen species, lipid peroxidation, caspase independency and the possible involvement of autophagy. These observations lead us to hypothesize that ferroptosis may also be involved in cancer cell death due to pharmacologic ascorbate treatment and in liver cell death due to acetaminophen overdose. Thus cell death of HT-1080 or cell line primary mice hepatocytes was induced by ferroptosis inducers and pharmacologic ascorbate or by acetaminophen overdose then the mechanism of cell death was compared.
Tibor Vellai: The regulation and mechanism of the aging process
Despite its medical, social and economic significance, understanding the mechanism of the aging process remains a fascinating and fundamental problem in biology According to our results, aging may be driven by genomic instability caused by the lifelong, progressive mobilization of mobile genetic elements (MGEs, also called “jumping genes”), which constitute major parts of eukaryotic genomes. Piwi proteins effectively repress MGEs in non-aging cells such as germline and cancer stem cells, while these proteins remain unexpressed in aging somatic cells. The regulation of the aging process is mainly achieved by EDTP/MTMR14 myotubularin-like lipid phosphatases that increasingly block autophagy in several cell types during adult lifespan.
Beáta Vértessy: Capturing the elusive uracil-DNA pattern
The true chemical space of DNA is much wider than previously thought, however, it is still a considerable task to decipher the real chemical composition and sequence of the genomic material. Using a novel approach, we have developed a protein sensor to capture uracil moieties in DNA for both Chip-sequencing and in situ super-resolution microscopy. The pattern of uracil distribution show intriguing characteristics and may shed light to the distribution of repair tasks among different DNA repair pathways.
We cordially invite you to the 10th MedInProt Conference held at ELTE TTK Eötvös lecture hall on Saturday, November 10, 2018 starting at 9 AM.
All interested are invited and welcome!
The eighth Conference of the MedInProt Protein Science Research Synergy Program was held on April 21. 2018, at Eötvös Loránd University.
Gergő Gógl: A crystallographer’s perspective on cryo-electron microscopy
The role of ion channels and pumps in tumor metastasis
Interaction of lysophosphatidic acid with signalling protein domains: affinity, stoichiometry and the site of binding
Role of the scaffold protein Tks4 in cancer cell movement
Setup of inflammation induced permeability measurements by gold nanoparticles and optical biosensor
Pathogenicity and oligomerization of podocin
Studying decision making process between cell death mechanisms: the GSH switch - ferroptosis and autophagy in focus
Investigation of the role of dynamin mediated and mitochondrial pathways in the background of centronuclear myopathy
Mihály Pósfai: New scientific directions in electron microscopy laboratory
Ferenc Vonderviszt: The revolution of cryo-electron microscopy in determination of biomolecular structures
Recent advances in cryo-electronmicroscopy have dramatically reshaped the landscape of structural biology. This technique can be used to determine the three-dimensional structure of biomacromolecules in near native conditions at close to atomic resolution, and has the potential to reveal multiple conformational states related to the dynamic behavior of molecular complexes. Cryo-EM now produces very excit¬ing results addressing a broad range of important biological questions with a level of detail we have never seen before.Ágnes Hubert: From protein sample to high-resolution cryo-electron microscopy map
Cryo-electron microscopy (cryo-EM), is an increasingly popular technique allowing the examination of a frozen-hydrated specimen in vitreous (non-crystalline) ice. The technique complements X-ray crystallography by revealing structural details without the need for a crystalline specimen. The workflow of single-particle cryo-EM is demonstrated with the case-study of three archaeal protein complexes and the structure of the eukaryotic 26S proteasome.Gergő Gógl: A crystallographer’s perspective on cryo-electron microscopy
I will discuss the advantages and the potential problems of cryo EM modelling in constrast to the conventional crystallographic structure determination.
László Nyitray: Resolution revolution
The Nobel prize in chemistry in 2017 was awarded to Jacques Dubochet, Joachim Frank and Richard Henderson for developing cryo-electron microscopy as a structural biology method. In the lecture the development of the Method of the Year in 2015 will be briefly described together with the contribution of the Nobel prize winners and further methodological progress in the last couple of years that explains the "resolution revolution".
Max Maletta: How Cryo-EM is changing the Structural Biology landscape for the best
In 2017 R. Henderson, J. Frank and J. Dubochet have been awarded the Nobel prize in Chemistry for having pioneered cryo electron microscopy (Cryo-EM) and Single Particle Analysis (SPA).
During the last few years Cryo-EM and SPA have grown from techniques able to produce low-resolution structures of protein complexes to tools capable of achieving atomic and quasi-atomic resolution for complexes that nobody could solve with any other technique.
This incredible leap forward has been made possible through the introduction and adoption of new tools, in particular direct electron detectors (DED), ultra-stable cryo-microscopes, such as the Titan Krios and the adoption of new SW for automatic data collection and processing.
Cryo-EM benefits of specific advantages, with respect to other structural biology techniques such as NMR and X-ray diffraction:
. Crystallization or isotopic labelling is not needed.
. The amount of sample required is two orders of magnitude lower.
. Different functional conformation of a protein complex may be revealed.
Cryo-EM has proven to be a very useful technique to be integrated with X-ray and NMR for structure-based drug design Thus it is no surprise that many structural biology groups all over the world are seeking access to this technology in order to find answers to their most relevant biological questions. Nevertheless most users that are new to the field of cryo-EM are struggling to overcome the adoption barrier that this technique may pose in terms of: sample preparation and screening, automatic data acquisition and progressive users training.
In this presentation we will present how the fast pace of cryo-EM growth is going to revolutionize the structural biology landscape. In addition, the latest Thermo Fisher Scientific technologies/solutions will be introduced:
- The cryo-EM SPA workflow with the recently introduced electron microscopes Krios G3i and Glacios - today the most economical and efficient Cryo-EM solutions for getting to the 3D structure of protein molecules.
- The recent advances in electron cryo-tomography with the cryo focused-ion-beam, an application for visualization of biological structures in their native, cellular context at the molecular-scale.
- The new development of mED (Micro electron Diffraction): a technology that holds the promise to solve the high resolution 3D structure of proteins crystallized into very small., an interesting cost effective alternative for XFEL.
We cordially invite you to the 7th MedInProt Conference held at ELTE TTK Eötvös lecture hall on Saturday, April 21, 2018 starting at 9 AM.
Winners of the Synergy VI., VII. and the Feasibility Study Program shall present their joint research at the conference. In addition, topic covers in cryo-EM Mihály Pósfai and Ferenc Vonderviszt will give lectures.
The conference will end with sweepstakes and poster discussions.
All interested are invited and welcome!
Az MTA Szerves és Biomolekuláris Kémiai Bizottság és a Kajtár-Hollósi Alapítvány tisztelettel meghívja Önt, barátait, tanítványait és minden kedves érdeklődőt a soron következő „Bruckner termi előadásra” és az Alapítvány emlékülésére
Időpont: 2017. december 1. péntek 14.00 óra
Helyszín: ELTE TTK Kémiai Épület, (1117 Budapest, Pázmány P. sétány 1/a)
The Molecular Frontiers Symposium was held on September 14-15. 2017, at Eötvös Loránd University.
Presented at the conference:
September 4. 2017, 4 p.m., MTA TTK
Molecular Frontiers (www.molecularfrontiers.org) is an international network formed by researchers and professors. This organization focuses on highlighting the importance of molecular sciences in a wide range of society, thus attracting young people towards science. Molecular Frontiers Symposia, organized for the upper purpose gathers leading scientists of the Globe, usually to discuss the topic of a current global problem. The actual issue and the attendees of these events are decided by the Scientific Committee (many members of which are Nobel laureate scientists); thus young student (age usually from 14 to 25) and other participants have the opportunity to meet the top researchers of the field. Further information regarding past events at: http://www.molecularfrontiers.org/symposia).
On each symposia 10 to 12 researcher hold lectures many of whom have received a Nobel Prize. On the demonstrating photo a group picture of the 2015 event in Göteborg can be seen. More than 1000 students and researchers attend Molecular Frontiers events, moreover, thanks to the recently initiated live broadcasting via internet, Molecular Frontiers Symposia are becoming rapidly expanding international events.
We believe that the Hungarian organization of such a prestigious event not only furthers molecular science’s popularity and recognition among the young, but also promotes the international (mostly inter EU) recognition of Hungarian research, thus, fulfilling an important national interest. The currently chosen topic shall follow the theme of an actual Hungarian program known as MedInProt initiative, with the purpose of assisting the communication among scientists working in the fields of protein sciences and pharmacology. The goal of MedInProt and Molecular Frontiers is to efficiently support the more successful integration of Hungarian scientists into the international network.
Vesse föl új és eredeti ötletét, akár még ma, nyújtsa be támogatási igényét, és a MedInProt kuratóriuma rövid megfontolás után, ha a kezdeményezést méltónak találja, azonnal támogatja is. „first come first served”.
Figyelmébe ajánlom „Megvalósíthatósági” programunkat (http://medinprot.chem.elte.hu/hu/palyazatok/uj-palyazatok)
- a szinergiában résztvevő kutatók közül legalább az egyik a 4 központi intézmény (ELTE, BME, MTA-TTK, SE) valamelyikében legyen főállású közalkalmazott,
- a javaslat világosan mutasson rá arra, hogy Ön és társa(i) az ad hoc támogatásnak köszönhetően hogyan jutnak közelebb hosszú távú a közös munkához és egy közös pályázáshoz akár hazai, akár nemzetközi fórumon.
Jelen „ad hoc” támogatás volumene:
200 eFt <= x <= 2M Ft (eltérés csak kiemelten indokolt esetben lehetséges)
Jelen „ad hoc” támogatás pályázási határideje:
2017. május 10.
Küldje el a firstname.lastname@example.org e-mail címre.
Budapest, 2017. május 2.
a MEDinPROT kuratórium elnöke
The sixth Conference of the MedInProt Protein Science Research Synergy Program was held on April 22. 2017, at Eötvös Loránd University.
Studying in vivo effect of cell-penetrating inhibitor peptide conjugate on protein-protein interaction
Gábor Mező: Development of bioconjugates and their modules for targeted treatment of cancers with high mortality rate
There is increased interest in peptide based targeting moieties for drug delivery in targeted tumor therapy, that recognize the specific or overexpressed receptors on tumor cells with high selectivity. Despite there are promising results with peptide – drug conjugates, their application in combination similarly to chemotherapy might have benefits. For this purpose we would like to develop molecular libraries which modules (drugs, homing peptides and bifunctional linkers) can be attach to each other in high combination to develop numerous conjugates suitable for targeted tumor therapy.
Beáta Vértessy: K-RAS oncogen mutations: structure-based allele specific inhibitor design
Balázs Győrffy: Investigating pediatric solid tumors with worst prognosis
Malignant diseases represent the leading cause of death for those below 14 years of age. While treatment of hemato-oncologic malignancies can almost completely heal a patient, half of patients with a solid tumor are lost within ten years. In our project we will gain new insights into the development of solid tumors by linking molecular and epidemiologic data.
We cordially invite you to the 6th MedInProt Conference held at ELTE TTK Eötvös lecture hall on Saturday, April 22, 2017 starting at 9 AM.
Winners of the Synergy V Program and the Grant Facilitating Access to Instruments Program shall present their joint research at the conference. In addition, NVKP winners Gábor Mező (ELTE), Beáta Vértessy (BME) and Balázs Győrffy (MTA) will give lectures.
The conference will end with sweepstakes and poster discussions.
All interested are invited and welcome!
The Protein Science Excellence Collaboration Program (MedInProt Program), sponsored by the Hungarian Academy of Sciences shall be expanded from 2017. Full-time researchers or professors working in an institute of the Academy’s research network or at any government financed institution of higher education may join the cooperation of ELTE, BMGE, SE and MTA-TTK employees. In the past three years several successful collaborations have started thanks to MedinProt. Due to the success the board has decided to expand the network of institutes from Spring 2017, thus, reaching a further step in the organizing a network of specialties.
MedinProt is a unique and essential initiative in Hungary with the following aims:
- Connecting, organizing and strengthening different protein science subfields
- Introducing the practice of competitive cooperation
- Catalyzing synergism among different fields of research
- Reinforcing and financially supporting the collaboration of acknowledged researchers
The Program mainly supports the following areas (from 2014):
1) The Synergy Program, announced every semester, provides a moderate, but regular financial support for the selected projects, in which 2-4 postdoctoral researchers can work together in solving a new and promising problem of protein science
2) The Access to Instruments Program, supports pairs of researchers whose research progress largely depends on recordings obtained by certain instruments, therefore, the fund covers the fees of using dedicated large instruments (X-ray, NMR, ESR, MS, etc.)
3) The Instrument Purchase Program is to support pairs of researchers whose scientific progress could significantly be furthered by the purchase of a large instrument (3 million HUF tops).
4) In the Mentor Program protein scientists with different backgrounds and positions may work together for a couple of weeks (2 months tops). The education of the PhD student/postdoc who is less experienced in the given field is supervised and supported by a chosen “mentor”.
5) The Summer School Program provides the opportunity to learn any kind of protein science related technique or to expand ones knowledge in the use of a large instrument, during few-day technical workshops for small groups.
6) The Feasibility Program offers a one-time support (1 million HUF tops) for protein science-related preliminary studies necessary for the application to large national or international grants
Conditions of the application:
1) potential applicants are required to register on MedinProt’s homepage
2) New candidates should apply together with researchers of the previously eligible institutes (ELTE, BMGE, SE and MTA-TTK), they must join the research of one of the upper institutes, thus, strengthening the national synergy.
In each case, submitted applications shall be reviewed by a board of eight members.
March 8. 2017. 4 p.m. MTA TTK Kisterem
February 8. 2017. 4 p.m., MTA TTK Kisterem