Laboratory of Molecular Instruments for Neurobiology

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Who are we?

The laboratory was formed in 2017 from a preexisting group that was officially organized in 2014 under the "Molecular and Cell Biology" Program of the Presidium of the Russian Academy of Sciences, concomitantly with the Department of Molecular Neurobiology (de facto the group was active since 2008). We are a young and ambitious team and we are always open for new members. Graduate and PhD students are most welcome!

What are we doing?

  1. Study of under-investigated natural venoms and poisons from jelly fish, centipedes, certain spiders, leaf beetles, sea urchins, and stingrays.
  2. Design and production of molecular instruments for neuroscience.
  3. Production of diagnostic tools and search for drug hits.

 

Our international partners:

Toxicology and Pharmacology, KU Leuven (Belgium). Head, Professor Jan Tytgat.

Experimental Anesthesiology and Pain Research, University Hospital of Cologne (Germany). Head, Professor Tim Hucho.

Maduke Lab, Stanford University (USA). Head, Professor Merritt Maduke.

Kullmann Lab, Institute of Neurology, University College London (UK). Head, Professor Dimitri Kullmann.

Sobolevsky Lab, the Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center (New York, USA). Head, Professor Alexander Sobolevsky.

NamePositionContacts
Alexander Vassilevski, Ph.D.depart. dir.avas@ibch.ru+7(495)336-65-40
Petr Oparin, Ph.D.r. f.spud-13@mail.ru+7(495)336-65-40
Alexey Kuzmenkov, Ph.D.r. f.aleksey.kuzmenkov@gmail.com+7(495)336-65-40
Antonina Berkutj. r. f.Problemka2008@gmail.com+7(495)336-65-40
Maria Sachkova, Ph.D.j. r. f.sachkovamasha@mail.ru+7(495)336-65-40
Anton KommerPhD stud.lipokuza@rambler.ru+7(903)6750157
Nikita Kuldyushevstud.nikita.kuldushev@phystech.edu+7(495)336-65-40
Tat'yana Kotovat. q. - lab. as.
Daniil Lukyanovt. q. - lab. as.
Andrei Gigolaevres. eng.gig-andrey@yandex.ru
Ivan Chudetskiyres. eng.ivan.chudetskiy@gmail.com
Zhanna Kanaevskayalab. as.zh-kanewskaya@yandex.ru+7(495)000-00-00

Selected publications (show all)

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Alexander Vassilevski

  • Russia, Moscow, Ul. Miklukho-Maklaya 16/10 — On the map
  • IBCh RAS, build. 51, office. 365
  • Phone: +7(495)336-65-40
  • E-mail: avas@ibch.ru

Spider toxin inhibits aberrant currents in mutant ion channels (2018-12-03)

Toxin from the venom of the crab spider Heriaeus melloteei may serve as a hit in drug discovery for hypokalemic periodic paralysis type 2; there is no reliable medication for all cases of this disease. It is caused by mutations in the gene encoding voltage-gated sodium channels NaV1.4, characteristic of skeletal muscles. As a result of the mutations, these channels conduct aberrant currents, the muscles are unable to respond to the signals of the nervous system, and weakness develops followed by paralysis. Hm-3 toxin was found to be able to selectively inhibit such currents through voltage-sensing domain I of mutant channels. Read more in the press release on the IBCh website.

Publications

  1. Männikkö R, Shenkarev ZO, Thor MG, Berkut AA, Myshkin MY, Paramonov AS, Kulbatskii DS, Kuzmin DA, Castañeda MS, King L, Wilson ER, Lyukmanova EN, Kirpichnikov MP, Schorge S, Bosmans F, Hanna MG, Kullmann DM, Vassilevski AA (2018). Spider toxin inhibits gating pore currents underlying periodic paralysis. Proc Natl Acad Sci U S A 115 (17), 4495–4500

Molecular mechanism of action of acylpolyamines, glutamate receptor blockers (2018-12-03)

Spiders and wasps secrete in their venom acylpolyamines that act as high-affinity blockers of receptors for glutamate, the main excitatory neurotransmitter of the human brain. Under the leadership of Eugene Grishin in 1986, the first representative of acylpolyamines was described, namely, argiopin from the venom of the orb-weaver spider Argiope lobata. In 2018, the spatial structure of argiopin complex with a glutamate receptor was studied using cryo-electron microscopy. The obtained results will allow the creation of drugs for the treatment of neurodegenerative diseases. The study was featured on the cover of Neuron. Read more in the press release on the IBCh website.

Publications

  1. Twomey EC, Yelshanskaya MV, Vassilevski AA, Sobolevsky AI (2018). Mechanisms of Channel Block in Calcium-Permeable AMPA Receptors. Neuron 99 (5), 956–968.e4

Mode of selective action of Kv1.2 potassium channel blocker (2018-12-03)

Scorpion venom is rich in peptide blockers of voltage-gated potassium channels (KV), and we have reflected this diversity previously in Kalium, a database dedicated to such peptides. A high-affinity and selective blocker of KV1.2 channels, characteristic of the human central nervous system, was obtained from the venom of the scorpion Mesobuthus eupeus. Using molecular modeling and site-directed mutagenesis, the mechanism of selective interaction between the toxin and channels was investigated.

Structure of two-domain spider toxins (2017-11-28)

Venoms of many spiders contain two-domain toxins that unite in their structure modules, which are similar to "simple" single-domain toxins. We conducted a detailed structural study of those toxins that consist of disulfide-rich (similar to ordinary neurotoxins) and linear (similar to conventional cytotoxins) modules. Linear modules can serve for the association of two-domain toxins with membranes due to the formation of amphiphilic helices, characteristic of membrane-active peptides. We propose a "membrane access" mode of action for two-domain toxins: linear modules interact with lipid bilayers, whereas disulfide-rich modules bind to protein receptors.