Jelena Baranovic

Biophysics of AMPA-type glutamate receptors.

Jelena Baranovic is a lecturer in biochemistry at the School of Biological Sciences, Institute for Quantitative Biology, Biochemistry and Biotechnology (IQB3). She joined IQB3 in September 2018, after her postdoc at the Leibniz Institute for Molecular Pharmacology, Berlin, Germany in the lab of Prof. Andrew Plested. She obtained her PhD at the Department of Physics, University of Oxford in the group of Prof. John Ryan. 

Her work focuses on the biophysics of ion channels, specifically AMPA-type glutamate receptors – ion channels in our brain critical for memory formation and learning.  

portrait photo of Jelena Baranovic
Jelena Baranovic

To understand how AMPA receptor structure endows them with millisecond kinetics needed for synaptic signalling, she uses and develops methods to trap and modulate the receptors in various conformational states, while monitoring their activity, at single-molecule and macroscopic level, in the cellular and artificial membranes. 

These results lead to the understanding of glutamate receptor gating and aid development of new tools to manipulate synaptic transmission, with a potential to direct new therapies for the central nervous system disorders, such as epilepsy and complex neurodevelopmental syndromes.

You can read more about Jelena here:

Early Career Researcher Spotlight (Nature Communications Biology) 

Alexander Edwards, John Girgis, Chigdem Arslan


We think, learn, memorise and forget because our neurons communicate in a certain way. Many proteins mediate this communication and AMPA-type glutamate receptors are among the most important ones. Their activity is one of the first signs to a neuron that another, neighbouring neuron is trying to communicate.

To understand what happens in our neurons when we learn, form memories and forget, we need to know how AMPA receptors work and how their activity is regulated. 

Our group uses a range of biophysical and molecular biology techniques to study function and regulation of AMPA receptors with the focus on the following questions:

1. What is the role of individual subunits in AMPA receptor activation?

AMPA receptors are composed of four core subunits whose structure and assembly are well studied, but how this links to function is not yet fully understood. The activation/deactivation cycle of AMPA receptors is extremely fast (it happens on a millisecond timescale). Currently, none of the available techniques that measure AMPA receptor activation is fast enough to observe activation of individual subunits. We are developing approaches to slow down AMPA receptor activation in order to overcome this limitation. This will allow us to observe how individual AMPAR receptor subunits contribute to its function. It will also help us understand how certain mutations affect AMPA receptor activity leading to complex neurological disorders.

2. Can we utilize nature's resources to develop a new generation of labels and modulators for endogenous AMPA receptors?

Synapses are very narrow spaces packed with proteins forming a dynamic network of close interactions and undergoing constant protein turnover. Careful positioning of AMPA receptors and other synaptic proteins within this dense network is essential for transmission of signals between neurons on a millisecond timescale. This is a challenging environment for a label or a modulator to navigate without disrupting the interaction network of endogenous AMPA receptors. We are developing a new generation of tools to study AMPA receptors inspired by a naturally occurring snail peptide called Con-ikot-ikot. Our aim is to minimise the disruption to AMPA receptor physiological environment. These novel labels and modulators would allow us to study the native function of AMPA receptors in fundamental cognitive processes, such as memory formation and learning, with minimal perturbations to their size and interaction network.  


multi panel research article figure

Figure 1. Structure and mechanism of action of Con-ikot-ikot, an AMPA receptor-specific peptide produced by sea snail Conus striatus.

(A) Crystal structure of an AMPA receptor in complex with Con-ikot-ikot (CII; PDB: 4U5D, Chen et al., 2014, https://doi.org/10.1126/science.1258409); AMPA receptor subunits are colour-coded: green (A), red (B), blue (C) and yellow (D), CII toxin is in magenta. AMPA receptor domains are indicated as: ATDs – amino-terminal domains, LBDs – ligand-binding domains and TM – transmembrane region.

(B) Network analysis of interactions between AMPA receptor and CII, as captured by molecular dynamics simulations of the complex. The network shows all the interactions of CII with AMPA receptor ligand-binding domains (LBDs); the inset on the right hand-side highlights the positions of the top 10 CII residues driving the toxin interactions with AMPA receptor LBDs. 

(C) Network analysis data (weighted degree, blue dots) are compared with the computational alanine-scanning data of the CII – AMPA receptor complex (interΔΔG, red line). The thermodynamics of interactions between individual CII residues and AMPA receptor LBDs from the computational alanine scanning agrees well with the data from the network analysis which focuses primarily on the frequency and type of interactions. 

(D) Activity of a single AMPA receptor in complex with CII toxin was recorded in the presence of glutamate (10 mM), at -80 mV (grey trace). The single-receptor activity was recorded with outside-out patch-clamp technique. Analysis of the activity (overlaid black trace) identified 5 different states in which a CII-bound AMPA receptor can exist: closed state (C) and 4 different open level (O1-O4) with O1 indicating the open state with the lowest conductance and O4 the highest conductance. The occupancy and frequency of visits to these individual states are quantified in the plots below. Compared to two other main modulators of AMPA receptors, CTZ and (R,R)-2b, which both block AMPA receptor desensitization, just like CII, CII forces AMPA receptor into frequent visits to the closed state and is a poor stabiliser of the O4. 

Baranovic, J., Braunbeck, S., Zaki, N., Minniberger, S., Chebli, M., Plested, A. J. R.: The action of Con-ikot-ikot toxin on single AMPA-type glutamate receptors, Journal of General Physiology, 2022, 154(5): e202112912; https://doi.org/10.1085/jgp.202112912

Baranovic, J., Plested, A. J. R.: Auxiliary subunits keep AMPA receptors compact during activation and desensitization, eLife 2018, e40548, https://doi.org/10.7554/eLife.40548

Baranovic, J.: AMPA receptors in the synapse: very little space and even less time, Neuropharmacology, 2021, 196, https://doi.org/10.1016/j.neuropharm.2021.108711

Baranovic, J., Plested A.J.: Single-Channel Recording; The handbook of electrophysiology: a practical guide for neurophysiologists, World Scientific Publishing Co Pte Ltd, Nov 2025, ISBN 10: 9819813751


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