10. Conference of MedInProt - visiting lecturers 2018-10-29

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 instrumentSzilvia 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.

Book Launch: Ezerarcú fehérjék

10. Conference of MedinProt 2018-10-29

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!