​PhD Advisor: Professor Manuel Aranda

Abstract:
Many omics-level studies have been undertaken on Aiptasia, however, our understanding of the genes and processes associated with symbiosis regulation and maintenance is still limited. To gain deeper insights into the molecular processes underlying this association，we investigated this relationship using multipronged approaches combining next generation sequencing with metabolomics and immunohistochemistry.
We identified 731 high-confident symbiosis-associated genes using meta-analysis. Coupled with metabolomic profiling, we exposed that symbiont-derived carbon enables host recycling of ammonium into nonessential amino acids, which may serve as a regulatory mechanism to control symbiont growth through a carbon-dependent negative feedback of nitrogen availability to the symbiont.
We then characterized two symbiosis-associated ammonium transporters (AMTs). Both of the proteins exhibit gastrodermis-specific localization in symbiotic anemones. Their tissue-specific localization consistent with the higher ammonium assimilation rate in gastrodermis of symbiotic Aiptasia as shown by 15N labeling and nanoscale secondary ion mass spectrometry (NanoSIMS). Inspired by the tissue-specific localization of AMTs, we investigated spatial expression of genes in Aiptasia. Our results suggested that symbiosis with Symbiodiniaceae is the main driver for transcriptional changes in Aiptasia. We focused on the phagosome-associated genes and identified several key factors involved in phagocytosis and the formation of symbiosome. Our study provided the first insights into the tissue specific complexity of gene expression in Aiptasia.
To investigate symbiosis-induced response in symbiont and to find further evidence for the hypotheses generated from our host-focused analyses, we explored the growth and gene expression changes of Symbiodiniaceae in response to the limitations of three essential nutrients: nitrogen, phosphate, and iron, respectively. Comparisons of the expression patterns of in hospite Symbiodiniaceae to these nutrient limiting conditions showed a strong and significant correlation of gene expression profiles to the nitrogen-limited culture condition. This confirmed the nitrogen-limited growing condition of Symbiodiniaceae in hospite, and further supported our hypothesis that the host limits the availability of nitrogen, possibly to regulate symbiont cell density.
In summary, we investigated different molecular aspects of symbiosis from both the host’s and symbiont’s perspective. This dissertation provides novel insights into the function of nitrogen, and the potential underlying molecular mechanisms, in the metabolic interactions between Aiptasia and Symbiodiniaceae.

Bio:
I am a molecular biologist focusing on the metabolic interactions in the cnidarian-dinoflagellate symbioses. Before coming to KAUST, I developed my expertise in a broad range of molecular, cellular, and biochemical techniques, and mainly focused on the research of plant science and structure biology. In my PhD studies, I developed and optimized several molecular tools to investigate the interactions between Aiptasia and Symbiodiniaceae in their symbiotic relationship. I aimed to integrated information from multiple omics levels to better understand the underlying molecular mechanisms, and validate the hypotheses raised from omics studies with different laboratory techniques at fine scales.

​Abstract:
With the conclusion of the human genome-sequencing project, the biological and medical research community has an unparalleled opportunity to understand and cure diseases on a genetic level. However, translating this genomic information into drug therapies is still a major challenge facing researches in the fields – up to the pre-clinical stage – as well as pharmaceutical companies for the later stages of development. Providing support for the concept that drug modulation of a given target is likely to produce a therapeutic response in patients is a key step in this progression from “gene to screen”. The main limitations are knowing which gene products are functionally involved in the pathology of a disease (target validation) and the druggability of the gene products by natural and/or synthetic compounds. Another major limiting step in the virtuous cycle “from bench to bed and back” is set by the successful targeted delivery in gene/drug therapy. Living organisms are in fact generally well protected by intra- and extracellular barriers against invasion of foreign genetic material. This is required to ensure the genetic stability of the species. Therefore, any gene delivery system (GDS) has to be designed to overcome these barriers. Under this general perspective, in this talk we will illustrate in detail several examples of integrated and multidisciplinary approaches in personalized medicine. Specifically, we will present issues related to cancer targeted therapies, diagnostics, resistance to cancer treatment, transmembrane receptors biology, characterization and drug development, and design, development and testing of nanovectors for gene therapy.

Bio:
Current acadmic position
20/2/2002-today Associate Professor, Italian Scientific Sector ING-IND/24: Principles of Chemical Engineering, Depertment of Engineering and Architecture (DEA), University of Trieste, Trieste, Italy
2012-today National Scientific Habilitation to Full Professor, Italian Scientific Sector BIO/11: Molecular Biology.
My scientific background includes expertise in computational and wet-lab chemistry, biological chemistry, molecular biology, computational and experimental structural biology, and multiscale bio-molecular simulations.
As a scientist, my main research focus is on protein structure, function targeted therapies and drug resistance phenomena in cancer and other major human diseases. I am the scientific leader of the MolBNL@Units (Molecular Biology and Nanotechnology Laboratory of the University of Trieste), a computational and experimental facility in which we 1) express, purify and characterize - from the structural, chemico-physical and biological perspective - mutant proteins as pathological drivers/hallmarks, 2) predict/determine their structure, stability and behavior per se and in complex with e.g., small molecule inhibitors, other proteins and nucleic acids (e.g., binding thermodynamics, kinetics and stability) via a combined in silico/experimental approach, and 3) determine their activity in cellular-based assays. Besides experimental facilities (which include last generation instrumentation for the above-mentioned activities), the laboratory is equipped with top-edge computational hybrid CPU-GPU clusters and granted access to all European HPC centers for performing all multi-scale molecular simulations activities.
As an educator, I am currently teaching classes of Thermodynamics, Organic and Biological Chemistry, Molecular Biology, and Molecular Simulation Techniques for undergraduate and graduate students in Industrial/Materials and Process/Biomedical Engineering, and Pharmaceutical Chemistry and Technology. In the last 10 years, I have supervised 350+ undergraduate/graduate students in Materials and Process Engineering and Pharmaceutical Chemistry and Technology. As an expert in multiscale molecular simulations, I have been appointed by the European Commission as officer expert/evaluator for the monitoring/evaluation of all European HPC centers of excellence and bio-based HPC proposals evaluation under the H2020 framework program.
University of Trieste MSc 1980-1986 Chemistry
Stevens Institute of Technology  Fellowship 1986-1987  Biomacromolecular Chemistry and Physics
Universities of Padua and Trieste PhD 1987-1990 Chemical Engineering

​Hosts: Prof. Lukasz / Prof Maurisz Jaremko
 
Abstract:
Chromosomal translocations that affect the MLL (Mixed Lineage Leukemia) proto- oncogene occur in aggressive acute leukemias, both in children and adults. Fusion of MLL to one of more than 60 partner genes results in generation of the MLL fusion oncoprotein, which ultimately leads to the development of acute leukemia. Patients harboring MLL translocations poorly respond to available therapies emphasizing the urgent need for novel therapeutics. Leukemogenic activity of MLL fusion proteins is dependent on their interaction with protein called menin, and selective targeting this protein-protein interaction with small molecules could block the oncogenic activity of MLL fusion proteins and abrogate development of acute leukemia.
Through the extensive studies involving combination of high-throughput screening, structural biology and medicinal chemistry we developed very potent small molecule inhibitors blocking the menin-MLL interaction at low nanomolar concentrations. Treatment of MLL leukemia cells with these compounds results in inhibition of leukemia cell proliferation, downregulation of downstream target genes and leads to cellular differentiation. Structural studies revealed that these compounds bind to the MLL pocket on menin and mimic the key interactions of MLL with menin. Optimization of activity and drug-like properties led to the development of very potent menin inhibitors active in vivo in animal models of MLL leukemia.
Through the extensive work, we have demonstrated the feasibility of targeting complex and high affinity protein-protein interaction with small molecule compounds. This work paves the way towards development of novel therapeutic approach for the treatment of very aggressive leukemias with MLL translocations and other leukemia sub-types. In this presentation, I will also describe challenges and opportunities to develop potent drug-like small molecule inhibitors to block protein-protein interaction in cancer in academic laboratory.
 
Bio:
Dr. Cierpicki is an Associate Professor in the Department of Pathology at the University of Michigan. He received MSc in chemistry from the Department of Chemistry, Wrocław University of Technology in Poland and PhD in biochemistry from the Department of Biochemistry and Molecular Biology; University of Wrocław in Poland. His research interest is in the area of chemical biology and cancer epigenetics. His laboratory has developed first-in-class inhibitors of the menin-MLL interaction as a new potential therapeutic strategy in MLL leukemias. His current efforts are focused on development of small molecule inhibitors targeting cancer related epigenetic proteins. He is co-author of over 80 peer review publications and inventor of over 10 patents.

​

SPEAKER 1: Sreekiran Pillai
TITLE: Understanding Hydrophobic Interactions between Rigid Macroscopic Surfaces Across Various Protic Solvents

Abstract:
Engineers routinely characterize hydrophobic surfaces by measuring contact angles, , of water droplets on them – if , surfaces are classified as hydrophobic. Despite this simple assessment, the fundamental nature of the hydrophobic interaction, defined as the attractive force experienced by two hydrophobic surfaces across water, remains unclear. Specifically, molecular-scale insights into the distance-dependence of the hydrophobic interaction and, the effects of adsorption of ions and evolution of hydrogen bonded percolation networks at water-hydrophobic interfaces are not entirely clear. Detergency and self-assembly process in air, oils and perflurocarbons are common examples of hydrophobic interactions. However, despite its ubiquitosness, mechanistic insights into hydrophobic interactions between extended surfaces remain elusive.  To resolve those issues we quantified hydrophobic interactions between molecularly-smooth mica surfaces terminated with perfluorodecyltrichlorosilane (FDTS) molecules in a variety of aqueous solutions, including 10 mM KCl water and heavy water, methanol, ethanol, and isopropanol, and 10 mM aqueous solutions of KBr, KI, KClO4, KPF6 using the Surface Force Apparatus (SFA). Intriguingly, we found that the hydrophobic interaction was stronger in light water compared to heavy water. This difference in hydrophobic interaction comes up when most of the physical properties of light water and heavy water are the same. My seminar will be a brief talk about the SFA technique used for the force measurement studies followed by the results and backed up by molecular dynamic simulations.

Bio:
Sreekiran Raveendran Pillai received his M.Tech in Chemical Engineering from Indian Institute of Technology (I.I.T) Bombay in 2014 with an All India Rank of 148, where he worked under Prof. Sarika Mehra and Prof. Rama Govindarajan. He joined Interfacial Lab in WDRC during the Fall of 2015. Currently he is pursuing his PhD in the department of Environmental Engineering under the supervision of Prof Himanshu Mishra. His research interest includes surface engineering, hydrophobic interactions and interfacial engineering.

SPEAKER 2: Adair Gallo Junior
TITLE: Superhydrophobic Sand Mulches Reduce Water Needs and Improve Yields in Desert Agriculture

Abstract:
Global demands for food and water are expected to rise by more than 50% by 2050 in order to sustain a projected population of 9.3 billion; and climate change could further exacerbate the constraints. Thus, higher crop yields will need to be achieved considering the limited surface and groundwater reserves. In response, we present an inexpensive granular superhydrophobic mulch as a potential solution. Comprising of ordinary sand grains with an approximately 20 nm-thick coating of paraffin wax, our superhydrophobic sand mulch dramatically suppresses evaporative loss when placed as a ~5 mm layer on topsoil. As a result, the average soil moisture content increases, leading to less stress for plants and consequently, higher yields. Field experiments for the past two years in Saudi Arabia demonstrate that the superhydrophobic sand mulch significantly enhances yields in tomato (Solanum lycopersicum) and barley (Hordeum vulgare) crops, relative to unmulched soils. The increased soil moisture also produced higher yields under irrigation with saline water (~5000 ppm). This novel technology has the potential to unlock new lands for agriculture and strengthen the food-water-energy nexus in arid regions, such as the Middle East.

Bio:
Adair Gallo Junior is a chemical engineer from Brazil. Cofounder of Massarani, a junior consultancy company specialized the areas of Chemical/Environmental Engineering. During his undergrad studies, he was awarded with the Science Without Borders scholarship for a one-year exchange program at the University of Iowa, with a summer internship at Jacob Israelachvili’s lab at the University of California in Santa Barbara. There, Adair worked under the supervision of Dr. Himanshu Mishra on bio-inspired materials and interfaces. Adair received his Master’s degree from KAUST in 2017 and now he pursues his PhD in Environmental Science under the guidance of professor Mishra at the Interfacial Lab. Adair is developing methods for improving water usage efficiency in arid land agriculture by employing water repellent sands.

SPEAKER 3: Jamilya Nauruzbayeva
TITLE: Contact Electrification at Solid Water-Hydrophobe Interfaces

Abstract:
Electrical charging at the interfaces of water with hydrophobic media, including air, hydrocarbon oils, polypropylene, and perfluorocarbons, has been a subject of intense debate.^1-2 A variety of mechanisms have been proposed, including the dipole moment of water,³ and specific adsorption of hydroxides,⁴ cryptoelectrons,⁵ and most recently bicarbonate ions;⁶ this phenomena also connects to the acidity vs. basicity of the air-water interface.^7-8

Bio:
In this seminar, we will present our experimental investigation of charge transfer at the polypropylene-water interface clarifying this debate.Jamilya Nauruzbayeva received her bachelor's degree in Chemical Engineering from Nazarbayev University, Astana, Kazakhstan in 2015. During her studies, she had received a funded scholarship for a summer school at University College London (2013), became a co-founder of Society of Petroleum Engineers student chapter (2014) and organized in various events for the students, faculty and external guests. Her undergraduate research project focussed on treating produced water in collaboration with a local refinery. She joined KAUST in August 2015 as an MS student in the EnSE program and is currently conducting doctoral research in Professor Mishra's Group. Her areas of interest include contact electrification and wetting at water-hydrophobic interfaces.

References
1.  Agmon, N.; Bakker, H. J.; Campen, R. K.; Henchman, R. H.; Pohl, P.; Roke, S.; Thamer, M.; Hassanali, A., Protons and Hydroxide Ions in Aqueous Systems. Chem Rev 2016, 116 (13), 7642-7672
2.  McCarty, L. S.; Whitesides, G. M., Electrostatic charging due to separation of ions at interfaces: Contact electrification of ionic electrets. Angew Chem Int Edit 2008, 47 (12), 2188-2207.
3.  Vemulapalli, G. K.; Kukolich, S. G., Why does a stream of water deflect in an electric field? J Chem Educ 1996, 73 (9), 887-888.
4.  Zimmermann, R.; Freudenberg, U.; Schweiss, R.; Kuttner, D.; Werner, C., Hydroxide and hydronium ion adsorption - A survey. Curr Opin Colloid In 2010, 15 (3), 196-202.
5.  Liu, C. Y.; Bard, A. J., Chemical Redox Reactions Induced by Cryptoelectrons on a PMMA Surface. J Am Chem Soc 2009, 131 (18), 6397-6401.
6.  Yan, X. B.; Delgado, M.; Aubry, J.; Gribelin, O.; Stocco, A.; Boisson-Da Cruz, F.; Bernard, J.; Ganachaud, F., Central Role of Bicarbonate Anions in Charging Water/Hydrophobic Interfaces. J Phys Chem Lett 2018, 9 (1), 96-103.
7.  Mishra, H.; Enami, S.; Nielsen, R. J.; Stewart, L. A.; Hoffmann, M. R.; Goddard, W. A.; Colussi, A. J., Bronsted basicity of the air-water interface. P Natl Acad Sci USA 2012, 109 (46), 18679-18683.
8.  Saykally, R. J., Air/water interface: Two sides of the acid-base story. Nat Chem 2013, 5 (2), 82-84.

​Host: Professor Himanshu Mishra
 
Abstract:
Chemical processes occurring at liquid interfaces are of profound importance in current scientific contexts ranging from catalysis and water purification to physiology, but the investigation of these systems presents significant obstacles to both theory and experiment.  We have developed several new experiments designed to elucidate vital details of aqueous interfaces, exploiting modern laser and light source technology.  Nonlinear spectroscopy in the deep ultraviolet region has been exploited to characterize the mechanism of selective ion adsorption to both the air/water and water/graphene interfaces.  Second harmonic generation scattering experiments have characterized the adsorption of neutral molecules to a series of polymer beads.  X-ray absorption spectroscopy has been used to characterize the interfacial distribution of aqueous carbonate species.  Recently developed soft X-ray free electron lasers have been used to perform the first second harmonic generation experiments in this region,  using graphite targets to demonstrate both high surface sensitivity and  strong resonance enhancement. These spectroscopic techniques are being used to investigate chemical reactions occurring at aqueous interfaces.  Details of these studies will be discussed.
 
Bio:
Richard Saykally is the Class of 1932 Endowed Professor at the University of California-Berkeley. Born in Rhinelander, Wisconsin and educated at UW-Eau Claire and UW-Madison, Saykally has been a professor at the University of California, Berkeley since 1979. He and his students have pioneered many important advances in spectroscopy, including velocity modulation spectroscopy of ions, terahertz laser vibration-rotation-tunneling spectroscopy of clusters, infrared photon counting spectroscopy, cavity ringdown spectroscopy, and X-ray spectroscopy of liquid microjets. These have permitted the first detailed study of important textbook molecules, including the hydronium (H3O+), hydroxide (OH-) and ammonium (NH4+) ions, as well as small water clusters and carbon clusters.
Recent work includes the spectroscopic determination of a universal water force field via the study of water clusters, the development of femtosecond nonlinear optical molecular imaging methods applied to single nanowire lasers and biological systems, femtosecond UV SHG/SFG studies of liquid electrolyte surfaces, and soft X- ray spectroscopy of liquids and liquid surfaces.
A co-author of over 400 publications that have been cited over 45,000 times (H index > 100), the recipient of over 75 honors and awards from 12 different countries, Saykally is a member of the National Academy of Sciences and the American Academy of Arts and Sciences, and has received the E.O. Lawrence Award in Chemistry from the U.S. Department of Energy, the Hinshelwood Lectureship from Oxford University, the Inaugural International Solvay Chair in Chemistry from the Solvay Institutes of Belgium, the Peter DeBye Award in Physical Chemistry from the ACS, the J.C. Bose Lectureship from IACS-Kolkata, and the Faraday Lectureship Prize from the UK Royal Society of Chemistry. He is a UC-Berkeley Distinguished Teacher, and has been active at the national level in science education. Over 150 students and postdocs have trained under his direction, many of whom hold prominent positions in academic, government, and industrial institutions.

​Host: Professor Stefan Arold

Abstract:
The seminar will focus on the use of gene editing to make xenotransplantation a clinical reality. We used CRISPR to eradicate all endogenous retroviruses from a pig genome [Niu et al. Science 2017] and are now making transgenenic pigs with up to 12 immune related gene edits. I will also briefly discuss how to improve safe gene delivery to the human genome and introduce our first steps in multiplex metagenome engineering.

Bio: 
Marc Güell - Assistant professor at Pompeu Fabra University
Marc's research interests are focused on technology development and clinical applications of Synthetic Biology. His laboratory is currently working on mammalian gene editing for therapeutic purposes as well as on metagenome and microbiome engineering. After a postdoc with George Church (Wyss Institute, Harvard University) he recently became a principal investigator and assistant professor at Pompeu Fabra University (Barcelona). He is a founding scientist at eGenesis Bio (xenotransplantation, egenesisbio.com) as well as co-founder of S-Biomedic (skin microbiome, sbiomedic.com).