Day 1 :
Keynote Forum
Annette G Beck-Sickinger
Leipzig University, Germany
Keynote: Structural insights in the binding mode of neuropeptide Y at G protein coupled receptors and consequences for drug development

Biography:
Annette G. Beck-Sickinger studied chemistry and biology at the University of Tubingen (Germany) and received her Ph. D. in organic chemistry. She was post-doc with E. Carafoli (Laboratory of Biochemistry, ETH Zurich) and appointed as assistant professor of Pharmaceutical Biochemistry at ETH Zurich. Since October 1999, she is full professor of Biochemistry and Bioorganic Chemistry at the University of Leipzig. She spent a sabbatical at Vanderbilt University (Nashville, TN) as visiting professor. Annette Beck-Sickinger was a member of the Board of the German Chemical Society (Gesellschaft Deutscher Chemiker, 2004-2012; Vice-President 2006-2008) and of the DFG panel "Biochemistry“ (2004-2012). Since 2017 she is member of the Board of the German Society for Biochemistry and Molecular Biology (gbm) and Vice-President. She has been awarded protein-coupledmany prices including the Leonidas Zervas Award of the European Peptide Society, the gold medal of the Max-Bergmann-Kreis (2009), the Leipzig Science Award (2016) and the Albrecht Kossel Award of the GDCh (2018). She was honoured with the membership of the Saxonian Academy of Science in 2009 and in 2012, she became an elected member of the German National Academy of Sciences Leopoldina. In 2017, she was awarded cross-linkingthe Saxonian Order of Merit. Her major reseach fields are structure-activity-relationships of peptide hormones and G protein coupled receptors and protein modification to study function and interaction. A tight connection of chemical methods, bioorganic synthesis and molecular biology tools, including cloning, receptor mutagenesis, protein expression and cell biochemistry is applied. Her interests include identification of novel targets and novel therapeutic concepts and novel approaches to modify proteins and concepts for improved enzyme catalysis and biomaterials.
Abstract:
- 3D Structure Determination| Computational Approaches in Structural Biology| Hybrid Approaches for Structure Prediction| Structural Bioinformatics and Proteomics
Location: Alto

Chair
Annette G Beck-Sickinger
Leipzig University

Biography:
Abstract:
Parkinson’s disease is caused by disruption of cells which provide dopamine to the striatum in the brain. Therefore, the main approach made for treatment of the disease has based on increasing dopaminergic signaling by using dopamine agonists, preventing dopamine breakdown via monoamine oxidase enzymes or supplying additional dopamine in the form of L-dopa. Even though L-dopa is known as the most effective drug so far, its efficacy decreases with time due to the use of high dosage of the drug. Moreover, it also causes motor complications such as motor fluctuations and dyskinesia. In this multidisciplinary project, we have aimed for developing hetero-bivalent ligands that target A2AR (Adenosine-2A-receptor)-D2R (Dopamine-2receptor) hetero-tetramer, which has been shown to be the dominant stoichiometry of A2AR-D2R. Firstly, we design and dock hetero-bivalent ligands to the receptors and investigate the molecular mechanism of allosteric interactions within the heterotetramer by means of accelerated molecular dynamics simulations. Subsequently, successful drug candidates are synthesized and tested in vitro for their activities. More importantly, the drug candidates are also tested by in silico and in vitro models for their permeation against blood-brain barrier. So far, hetero-bivalent ligands have been only used as molecular tools for detecting the existence of the receptor dimers. On the other hand, the current study will provide a chance to test the capability of hetero-bivalent ligands for being used as therapeutic molecules. In this way, we expect to develop more effective therapeutic molecules to alleviate the symptoms of Parkinson’s disease hence increasing the quality of patient’s life
Biography:
Abstract:
Parkinson’s disease is caused by disruption of cells which provide dopamine to the striatum in the brain. Therefore, the main approach made for treatment of the disease has based on increasing dopaminergic signaling by using dopamine agonists, preventing dopamine breakdown via monoamine oxidase enzymes or supplying additional dopamine in the form of L-dopa. Even though L-dopa is known as the most effective drug so far, its efficacy decreases with time due to the use of high dosage of the drug. Moreover, it also causes motor complications such as motor fluctuations and dyskinesia. In this multidisciplinary project, we have aimed for developing hetero-bivalent ligands that target A2AR (Adenosine-2A-receptor)-D2R (Dopamine-2receptor) hetero-tetramer, which has been shown to be the dominant stoichiometry of A2AR-D2R. Firstly, we design and dock hetero-bivalent ligands to the receptors and investigate the molecular mechanism of allosteric interactions within the heterotetramer by means of accelerated molecular dynamics simulations. Subsequently, successful drug candidates are synthesized and tested in vitro for their activities. More importantly, the drug candidates are also tested by in silico and in vitro models for their permeation against blood-brain barrier. So far, hetero-bivalent ligands have been only used as molecular tools for detecting the existence of the receptor dimers. On the other hand, the current study will provide a chance to test the capability of hetero-bivalent ligands for being used as therapeutic molecules. In this way, we expect to develop more effective therapeutic molecules to alleviate the symptoms of Parkinson’s disease hence increasing the quality of patient’s life

Biography:
Meriem El Ghachi has completed her PhD from Paris University of Paris-Sud, France. He is a Post-doctorate at University of Liege, Belgium. She has published 17 papers in reputed journals.
Abstract:
Undecaprenyl-phosphate C55-P is a key lipid carrier of glycan intermediate required for the synthesis of a variety of cell wall polymers such as Peptidoglycan (PG), Lipopolysaccharides (LPS) O-antigen wall teichoic acids, capsular polysaccharide, common enterobacterial antigen, membrane-derivative oligosaccharides and exopolysaccharides. In bacteria, during peptidoglycan synthesis, the phospho-N-acetylmuramoyl (-pentapeptide) -N-acetyl glucosamine is the essential motif carried by the C55-P. The resulting lipid, C55-PP-MurNAc-(pentatpetide)-GlucNAc (lipid II), is translocated towards the periplasmic side by several putative flippases. The MurNAc-(pentatpetide)-GlucNAc is added to the elongating chains of PG and C55- P is released as C55- PP. This precursor is also provided by the de novo synthesis in the cytosol that is catalyzed by a Cis-Prenyl Pyrophosphate Synthase, UPPS, which successively adds eight isoprene units from C5-PP on farnesyl pyrophosphate. Two families of phosphatases can perform the subsequent dephosphorylation of C55-PP into C55-P, common to the in vitro synthesis and carrier lipid recycling. In E. coli, 1 BacA and 3 phosphatidic acid phosphatases 2 (PgpB, YbjG and LpxT), active on C55-PP have been identified. PgpB being also involved in the phosphatidyl glycerol metabolism and LpxT transferring the phosphate from C55-PP to lipid A. Whereas Bacillus subtilis has three C55-PP phosphatases 1 BacA (YubB) and 2 phosphatidic acid phosphatases 2 (YwoA and YodM). We obtained the structure of BacA using lipidic cubic phase method. The crystal structure at 2.6 A revealed an unexpected fold according to the previous biochemical studies. Moreover, we solved the structure of bsPgpB (yodM) in the presence and absence of its favorite substrate, phosphatidyl glycerol.
Ghazaleh Gharib
Sabanci University Nanotechnology Research and Application Center, Turkey
Title: Cloning, sequencing, purification and characterization of highly thermostable aspartate aminotransferase from Geobacillus thermopakistaniensis

Biography:
Abstract:
Sushil Tripathi
University of Helsinki, Finland
Title: Systematic transcriptomic profiling defines critical LKB1substrates in gastrointestinal tumorigenesis

Biography:
Sushil Tripathi is a postdoctoral researcher in University of Helsinki. He had completed his PhD from Norwegian University of Science and Technology, Norway.
Abstract:
Maryam Alobathani
University of Sharjah, UAE
Title: Prevalence of Non-syndromic hearing loss in UAE due to genetic mutation in Mitochondrial 12S rRNA

Biography:
Maryam Alobathani has completed her Bachelor studies in Biotechnology by age 22 from University of Sharjah and know she’s working as a laboratory supervisor and completing her Master studies at the same university.
Abstract:
Deafness is a disease of inability to hear referred as hear impairment or anacusis for those with low or no hearing. It’s important at all levels of health care due to their significant burden on affected individuals and societies. Hearing loss can be classified as partial or completely inability to hear. Deafness can occur due to different mutations in different human genome such as Connexin26 the most common deafness gene, CDH23, TMC1 and in mitochondria. mitochondrial organelle is ubiquitous in eukaryotic as intracellular double membrane structure. The main function of mitochondria is to synthesis ATP by OXPHS and plays important roles in cell death and oxidative stress control. Mutation in mitochondrial DNA cause OXPHS defects that leads to many diseases one of them is hearing loss as syndromic and non-syndromic deafness. Therefore, we aim in this research to identify the genetic causes of NSAHL underlying wide spectrum of congenital conditions in UAE population. This study focused on a non-syndromic deafness caused by mutation on a mitochondrial MTRNR1 gene that encodes 12SrRNA. 40 Samples were collected from unrelated NSHL UAE family members and screened using biological tools such as PCR, Genomic sequencing machines and Bioinformatics tools. Expert geneticist recruiting and clinically assessing the participant patients involved in this study.The main approaches proposed are: (i) homozygosity maps were used to localize the homozygous regions in each particular family, (ii) next generation sequencing platform used to sequence the whole-exome of an affected individuals to explore all variants including the pathogenic mutations, finally (iii) pathogenicity of the outcoming variant results validated or ruled out by performing functional assays. The study indicates two out of the total 40 samples of unrelated UAE families with deafness due to mitochondrial 12S rRNA mutation m.669 T>C and m.827A>G, as well some known polymorphisms. This study is part of other researches done on a larger scale on similar area of interest that will reach to figure out new mutation related to mtDNA 12S rRNA variations. This finding can also help in future genetic counselling, prenatal screening, and post-natal genetic diagnosis to prevent the prevalence of more NSHL patients.