Rappaport Faculty of Medicine
Graduate Thesis Seminars

Speaker: Shunit Olszakier, B.Eng.
Assistant Professor Lilac Amirav, Faculty of Chemistry
Assistant Professor Itamar Kahn, Faculty of Medicine
Title: Intracellular Labelling of Selected Neurons Utilizing MR-visible Nanoparticle Imaging
Date: Jan 29, 2017
Time: 12:00-13:00
Place: 4th Floor Seminar Room

A central goal of diagnostic medical imaging is to characterize the cellular integrity of brain cells when degenerative processes are on-going but prior to massive cell death that results in gross atrophy. Magnetic resonance imaging (MRI) is a commonly used method in humans and animals able to measure gross integrity. Current intrinsic and contrast agents, however, cannot distinguish between the intra and extra-cellular environments. In my thesis, I developed a novel class of nanoparticles that are dually compatible in both MRI and conventional optical microscopy, allowing the high contrast imaging of the intracellular environment. My research was focused on the establishment of a platform to characterize and optimize these particles for the intracellular environment of neurons and MRI. Ultra-small superparamagnetic Iron Oxide nanoparticles (USPIOs) exhibit strong magnetization that induces microscopic field inhomogeneity in the presence of an external magnetic field. Due to their small size, USPIOs are optimal for internalization into cells with minimal disturbance to biological processes. Testing their effects on cells at the microscopic level required additional labeling of the USPIOs using a fluorescent marker. Quantum dots are considered preferable fluorescent components due to their high temporal stability and resistance to photobleaching compared with dyes. Hence, I combined USPIOs with CdSe@CdS core (a subclass of quantum dots). Our magneto-fluorescent nanoparticles were designed with a unique morphology that prevented undesirable interactions within the hybrid that could abrogate the respective properties. Synthesis of these magneto-fluorescent nanoparticles yielded a strong bi-functional nontoxic contrast agent. In a series of experiments I demonstrate the viability of these nanoparticles for intracellular characterization using MRI and optical microscopy. Our results suggest that imaging of cellular integrity using intracellular contrast agent is feasible.

Neuroscience Special Seminar | Dr. Yehezkel (Hezi) Sztainberg

Rappaport Faculty of Medicine
Search Committee Seminar

Speaker: Yehezkel (Hezi) Sztainberg, Ph.D.
Affiliation: Dept of Molecular and Human Genetics, Baylor College of Medicine
and The Jan and Dan Duncan Neurological Research Institute,
Texas Children’s Hospital
Title: Neurodevelopmental disorders: from basic science to novel therapeutic approaches
Date: Feb 1, 2017
Time: 13:30-14:30
Place: 4th Floor Seminar Room

Neurodevelopmental disorders encompass a wide range of childhood-onset medical conditions caused by different genetic mutations and interaction with environmental factors, affect ~2% of the population, and are a leading cause of intellectual disability and autism spectrum disorder. Evidence is accumulating that either loss or gain in dosage of proteins involved in cognitive and behavioural processes can be deleterious to the nervous system by causing a failure in the ability to maintain neuronal homeostasis. My studies are focused on the MECP2 duplication syndrome, one of the most common genomic rearrangements in males, characterized by autism, intellectual disability, motor dysfunction, anxiety, epilepsy, recurrent respiratory tract infections and early death. To determine whether the phenotypes of MECP2 duplication are reversible upon normalization of MeCP2 levels, I first generated and characterized a new mouse model that over-expresses a conditional allele of Mecp2 that could be deleted in the adult animal (Nature 2015). Upon normalization of MeCP2 in adult symptomatic mice, several phenotypes were rescued at the behavioral, physiological, and molecular levels. Next, I reduced MeCP2 using an antisense oligonucleotide (ASO) strategy, which has greater translational potential. I found that ASO treatment induced a broad phenotypic rescue in adult symptomatic MECP2 duplication mice, abolished abnormal EEG discharges and behavioral seizures, and corrected abnormal gene expression in the hippocampus. I am currently characterizing a novel “humanized” mouse model of MECP2 duplication syndrome that will precisely mimic the human condition by having two copies of human MECP2 and no copies of the mouse gene. These mice will serve as the ideal model for preclinical tests as they represent the closest construct validity model for the human condition. In addition, I am generating and characterizing neurons induced from patients’ derived pluripotent stem cells (iPSCs).

Neuroscience Special Seminar | Dr. Mark Shein-Idelson

Rappaport Faculty of Medicine
Search Committee Seminar

Speaker: Mark Shein-Idelson, Ph.D.
Affiliation: Department of Neural Systems & Coding,
Max-Planck-Institute for Brain Research,
Frankfurt, Germany
Title: From dragons’ sleep to sliders’ sight: Explorations in ancestral cortices
Date: Jan 11, 2017
Time: 13:30-14:30
Place: 4th Floor Seminar Room

The emergence of the cortex and its dramatic increase in size during vertebrate evolution suggest that it employs valuable computations. However, despite decades of intensive research and major advances in our knowledge of the molecular machinery underlying cortical functions, we still lack an understanding of these computations. In my talk, I will suggest that new insights can be gained by studying “simpler” cortices which are found in extant reptiles. Reptiles are the only extant class except mammals to have a layered cortex and are closest to the common ancestor of all amniotes (mammals, reptiles and birds). The reptilian cortex has three-layers (in contrast to six layers in mammals) and contains subdivisions that are considered to be homologous to both the mammalian neocortex and hippocampus. Focusing on two examples: sleep in bearded dragons and visual processing in red eared sliders, I will suggest that studying reptiles can provide a new understanding of the evolution of brain activity. In addition, reptilian brains can serve as a valuable model system for understanding population dynamics during sleep and wakefulness and may expose fundamental computational principles shared by all amniotes.