Project: The function of the ionotropic glutamate receptor NMDA in myeloid cells.

I am Tiago, a biologist who graduated at the São Paulo State University – UNESP, Brazil. I also have a master's degree in immunology from University of Sao Paulo, Brazil. In 2021, I joined the Laboratory of Neuroimmune Interactions as a PhD student. Currently, my research focuses on evaluating the role of the ionotropic glutamate N-Methyl-D-Aspartate receptor (NMDAR) in immune cells during the experimental autoimmune encephalomyelitis, which serves as a model for multiple sclerosis in mice.

Mostly expressed in excitatory neurons, the NMDAR is an ion channel activated by glutamate, allowing the entry of calcium into the intracellular environment. This leads to further membrane depolarization and further synaptic activation. Glutamate is the most abundant excitatory neurotransmitter in the central nervous system, playing a crucial role in memory and cognition. However, excessive glutamate production can lead to excitotoxicity, causing neuronal death, which is well-documented in neurodegenerative diseases like stroke, multiple sclerosis, Alzheimer's, and depression.

Even though immune cells possess glutamate receptors, their exact function remains poorly understood. Therefore, my research aims to uncover the role of the NMDAR in this specific context, shedding light on the interactions between immune cells and glutamate signaling. Specifically, I am enthusiastic about investigating the role of NMDAR on myeloid cells, such as macrophages and dendritic cells, and how it modulates their function during neuroinflammation. 

This question is relevant and may add to the understanding on the role of neurotransmitters during neurological diseases such as MS. Also, it may pave the way for unconventional therapeutic targets.

Project: Immunomodulatory Role of Extracellular Vesicles in Experimental Autoimmune Encephalomyelitis

I am passionate about the biology of EVs and their function. My big goal is to investigate the immunomodulatory properties of Extracellular Vesicles derived from Uterine Mesenchymal Stem Cells (meMSC-MVs), as well as those derived from the Central Nervous System Extracellular Vesicles (EV-CNS). 

The uterus is a well-known suppressive environment for the promotion of embryo implantation and, thus, I believe it may be an interesting source of MSCs. To investigate their potential as a therapeutic tool, I use the Experimental Autoimmune Encephalomyelitis (EAE), the animal model of Multiple Sclerosis. 

So, through in vitro experiments and in vivo approaches, I focus on unraveling the mechanisms by which they suppress the immune response, for example through miRNAs, cytokines, or even the presence of organelles. Also, I am interested in the function of EVs released in vivo, either physiologically or under inflammatory stimuli. For that, I isolate EVs derived from the CNS of naïve or EAE mice. The point here is to investigate how EVs released in vivo modulated both local and distant immune responses. Moreover, it may provide insights into the identification of CNS biological markers during neuroinflammation.

Title: Role of mTORC1 and mTORC2 Complexes in Astrocytes in Neurogenesis and the Pathogenesis of Zika Virus-Induced Microcephaly in a Murine Experimental Model 

I am Lilian Gomes de Oliveira, a PhD candidate, and my research focuses on the role of mTORC1 and mTORC2 complexes in astrocytes during neurogenesis and the development of microcephaly caused by the Zika virus in a murine experimental model. I am currently a Fulbright recipient as a visiting scholar at Dr. Arnold Kriegstein Laboratory, UCSF.

The Zika virus (ZIKV) has become a major global health concern, especially due to its association with a surge in microcephaly cases in Brazil between 2015 and 2016. Despite this, much remains unknown about how the virus triggers this condition. ZIKV belongs to the Flavivirus family and exhibits a fascinating affinity for the central nervous system (CNS), particularly targeting neural progenitor cells (NPCs) and glial cells. In the CNS, astrocytes, which are abundant glial cells, play a crucial role in supporting neuronal metabolism. They achieve this by producing lactate through glycolysis, which serves as a vital energy source for neurons.

A significant aspect of astrocytes' function in the context of viral infections involves glycolysis activation, stimulated by antiviral cytokines like type I interferon (IFN). This process is crucial for establishing an antiviral state. The type I IFN receptor (IFNAR) triggers the activation of AKT, which, in turn, leads to the activation of important complexes known as mechanistic target of rapamycin complexes 1 and 2 (mTORC1 and mTORC2). These complexes are involved in translating interferon-induced genes (ISGs) and activating glycolysis.

Interestingly, previous studies have shown that ZIKV can inhibit both the type I IFN pathway and AKT-mTOR activation. As a result, the virus can potentially counteract the antiviral immune response and affect glycolysis, leading to neuronal damage and viral replication. In light of these findings, my research project aims to delve into the role of astrocytes in the development of ZIKV-induced microcephaly, with a specific focus on the mTORC1 and mTORC2 complexes, using a murine experimental model.

By gaining insights into the underlying mechanisms, my findings could contribute not only to a better understanding of this enigmatic infection but also to elucidating the processes responsible for CNS damage in infants with microcephaly. Ultimately this knowledge may pave the way for future therapeutic interventions aimed at mitigating the effects of the Zika virus.