Institute of Physiology (IPHYS) of the Czech Academy of Sciences (CAS) is inviting applications for PhD Research Projects.
PhD Project 1
Early processing of ionotropic glutamate receptors in rat and human neurons
N-methyl-D-aspartate receptors (NMDARs) are a subclass of glutamate receptors that play an essential role in mediating excitatory neurotransmission and synaptic plasticity in the mammalian central nervous system. Dysregulation of NMDARs plays a critical role in the aetiology of many neuropsychiatric disorders and conditions, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, epilepsy, anxiety, depression, bipolar disorder, schizophrenia, lupus erythematosus, and ischaemia. Thus, understanding the molecular mechanisms that regulate NMDARs is essential for designing effective therapies for these patients.
In this PhD project, you will use a combination of microscopy, biochemistry, and electrophysiology to investigate the molecular mechanisms that regulate the early processing and function of NMDARs in primary rat hippocampal neurones and induced human neurons derived from fibroblasts from patients with neuropsychiatric disorders. The results obtained from these experiments will increase our knowledge regarding the mechanisms by which neurons regulate the number, type, and function of surface NMDARs.
M.Sc. or equivalent in molecular biology, microbiology, (bio)chemistry or medicine; fascination by the complexity of neuronal functions.
Supervisors: Martin Horak, PhD
PhD Project 2
Neurosteroid modulation of NMDA receptors
N-methyl-D-aspartate (NMDA) receptors are a type of ionotropic glutamate receptors mediating fast synaptic transmission and essential for learning and memory. Abnormal function of NMDA receptors underlies many neurological and psychiatric diseases, including schizophrenia and neurodegenerative disorders. We use advanced electrophysiology, molecular biology, optogenetics, and microscopy to investigate the relationship between the structure and the function of NMDA receptor ion channels, to characterize molecular mechanisms of action of different pharmacological agents influencing them, and to study the physiological and pathological processes in which NMDA receptors participate. For details please see http://www.biomed.cas.cz/odd031/researchlv.html
We have identified different neurosteroid compounds with potentiating or inhibitory effects on NMDA receptors. This project will focus on a detailed study of the mechanisms of neurosteroid actions on NMDA receptors, synaptic transmission, and behavior, both under normal conditions and in selected biological models of neurological and psychiatric disorders.
Candidates should have a Masters’ degree in biological, medical or chemical subjects, or be due to complete their studies in this academic year. Experience in cell biology, molecular biology, or genetics would be an advantage. Candidates will be expected to undertake independent research in their chosen project.
Supervisors: Prof. Ladislav Vyklický, Ph.D., D.Sc.
PhD Project 3
The role of iGluR complex in the emergence and development of schizophrenia.
Ionotropic glutamate receptors (iGluRs) mediate excitatory synaptic transmission and are essential for processes of learning and memory formation. Dysfunction of AMPA and NMDA receptors underlies many neurological disorders including schizophrenia. Schizophrenia is a psychiatric disorder with a serious impact on a patient’s life. We aim to determine how gene variants of the glutamate receptor complex (excitatory synapse) contribute to the emergence and development of schizophrenia. We employ NGS, bioinformatics, structural and molecular biology and electrophysiology techniques to characterize the functional consequences of altered glutamate receptor complex gene variants. This project will contribute to the identification of potential cellular markers of schizophrenia.
Candidates should have a Masters’ degree in biological, medical, chemical or bioinformatics subjects. Experience in molecular biology, cell biology, or human genetics would be an advantage.
Supervisor: Ales Balik, PhD
PhD Project 4
The glutamate NMDA receptor as a target of novel drugs for the treatment of Alzheimer disease
1,2,3,4-tetrahydro-9-aminoacridine (THA) was the first approved (by FDA in 1993) multitargeted drug for the Alzheimer disease (AD) treatment. In the collaborative project with the Biomedical Research Center in Hradec Kralove and the National Institute of Mental Health in Klecany, you will help to design and characterize novel THA-based compounds acting at multiple targets, including the glutamate type of the N-methyl-D-aspartate receptors (NMDARs). Specifically, you will compare the effectivenessness of the FDA-approved and novel drugs on the NMDARs and the AD-related alterations, by performing:
- i.) whole-cell and single-channel patch-clamp recordings from the mammalian cell lines expressing the recombinant NMDARs,
- ii.) synaptic recordings (“NMDAR-EPSC”) from the cultured hippocampal neurons grown on the microislands,
- iii.) biochemical and microscopical analysis of the hippocampal neurons infected with the shRNA-expressing lentiviruses and the human neurons derived from the fibroblasts of the AD patients,
- iv.) behavioral studies on the AD animal models.
Applicant profile (requirements):
M.Sc. or equivalent in molecular biology, microbiology, (bio)chemistry or medicine; motivation to find novel drugs with unique mechanism of action.
Supervisor: Martin Horak, PhD