Murali Prakriya
Northwestern University, IL·Neuroscience
Calcium ions act as messages inside cells. They turn on genes, change metabolism, trigger cell division and help neurons store memories.
- Fields
Neuroscience
Biophysics
Pharmacology
- Topics
CRAC channels
Orai1
store-operated calcium entry
- Grants
- 2 known grants, through Apr 2031
What they work on
- Map the binding interface between the Orai1 channel and the calcium sensor STIM1. Use photocrosslinking with unnatural amino acids that can be locked in place by light.
- Solve cryo-electron microscopy structures of three gain-of-function Orai mutants, including a human disease mutation, and compare them with closed normal channels to reveal how the pore opens.
- Test how electrostatic interactions at the Orai1 channel gate drive pore opening by substituting fluorinated phenylalanine analogs.
- Define the roles of store-operated calcium entry in neurons and astrocytes in synaptic plasticity, metabolism, learning and memory. Use conditional Orai1 and STIM1 knockout mice, electrophysiology and behavioral tests.
- Explain the fast activation and unusual calcium dependence of neuronal SOCE, and test its role in inflammation-induced depression and neuropathic pain, using structural analysis and molecular dynamics simulations.
More about the research
One major route for calcium to enter cells is through CRAC channels (calcium release-activated calcium channels), also called store-operated channels. These channels open when the endoplasmic reticulum (ER), the cell's internal calcium store, runs low. The ER sensor protein STIM1 then moves to the cell membrane and directly opens pores made of Orai proteins. The lab studies how these channels open at the molecular level and what they do in the brain. Faulty channels are linked to immunodeficiency, allergies, inflammation and muscle disease.
Why it matters
Mutations in Orai channels cause human diseases such as immunodeficiency. The channels are also involved in allergy, inflammation, depression and chronic nerve pain. Learning how the channels open, and how disease mutations change this process, could guide the design of mechanism-based drugs. It could also establish Orai channels as new therapeutic targets for brain disorders such as inflammation-induced depression and neuropathic pain.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Mohamed Trebak
University of Pittsburgh, PA·Physiology
Determine how native ORAI1–3 calcium channels and STIM1/STIM2 ER calcium sensors move, associate, dissociate and are internalized at PM–ER junctions.
Huijuan Hu
Rutgers University-New Brunswick, NJ·Neuroscience
Determine whether deleting or knocking down STIM2, a calcium-store sensor, in the mouse spinal cord reduces chronic itch in models of chronic itch, including DNFB- and DCP-induced dermatitis.
Stefan Feske
New York University, NY·Microbiology & Immunology
Determine how calcium signals through CRAC channels activate the Ets family transcription factor Fli1, and how Fli1 controls the development of T follicular helper cells, the T cells that help B cells make antibodies.
The school
Northwestern University: 71 labs on PI Pages, $1.3B a year on research, 536 research doctorates a year.
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