Department of Molecular and Cellular Neurobiology

Head: Prof. Leszek Kaczmarek
e-mail: l.kaczmarek@nencki.gov.pl

 

The Department of Molecular and Cellular Neurobiology is composed of eight independent laboratories headed by Anna Filipek, Leszek Kaczmarek, Małgorzata Kossut, Katarzyna Łukasiuk, Katarzyna Nałęcz, Katarzyna Radwańska, Jakub Włodarczyk and Rafał Czajkowski. Individual research programs in the laboratories are all complementary and interdependent within the common research area of molecular and cellular neurobiology.

Calcium homeostasis and its impact on processes related to cell proliferation and differentiation is investigated by the group led by Prof. Filipek. In particular, the group studies the role of the calcium binding protein, S100A6, and its ligands: Sgt1, CacyBP/SIP and p53 in ubiquitination, cytoskeletal organization and cellular response to stress.
 

Prof. Kaczmarek’s group aim is to understand brain-mind connection. They have shown that matrix metalloproteinase, MMP-9 is produced and released at the excitatory synapses in response to enhanced neuronal activity to play a paramount role in the synaptic plasticity, learning and memory as well as in neuropsychiatric disorders, including epilepsy, alcohol addiction, schizophrenia, autism and bipolar disorder. Presently, their major research effort is focused on MMP-9 and its fundamental role in controlling morphological and functional plasticity of the excitatory synapses, especially in the central nucleus of the amygdala, which they have implicated as pivotal for the appetitive learning.

 

Epileptogenesis is the main theme of the group led by Prof. Łukasiuk. Molecular mechanisms and the role of altered gene expression that can lead to epilepsy and the design of new therapeutic strategies are investigated.


Neuronal mechanisms of learning and plasticity in adult and ageing brain are studied by Prof. Kossut and her team. The models of plasticity developed in her laboratory serve to measure the effects of genetic modifications, brain disease and trauma upon functioning of the cerebral cortex.

Membrane transporters, in particular the expression of carnitine and amino acid transporters in highly specialized brain cells, including those making the blood-brain barrier are investigated by Prof. Nałęcz. Other research topics cover carnitine and palmitoylcarnitine and their role in signal transduction pathways in differentiating neural cells.


Molecular bases of behaviour with a focus on learning and memory formation, in health and diseases such as alcohol addiction, are investigated by Prof. Radwańska and her colleagues. The role of kinases in the regulation of structural dendritic spine plasticity in these behaviours is a major area of their investigation.

Synaptic modifications regulated by extracellular matrix proteolytic modifiers is studied by Prof. Włodarczyk and his team. Specifically, they investigate the role of extracellular matrix proteins and cell adhesion molecules in synapse formation/stabilization and their influence on postsynaptic receptor composition. Imaging based techniques are used to assess the reorganization of activity patterns accompanied by local volumetric changes at the synapses.

 

Role of retrosplenial cortex in spatial memory is the main research interest of Dr. Czajkowski and his colleagues. They use a variety of modern behavioral, molecular an physiological techniques  address this issue.



Selected publications:

 

Czajkowski R, Jayaprakash B, Wiltgen B, Rogerson T, Guzman-Karlsson MC, Barth AL, Trachtenberg JT, Silva AJ. Encoding and storage of spatial information in the retrosplenial cortex. Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):8661-6

 

Czajkowski R, Sugar J, Zhang SJ, Couey JJ, Ye J, Witter MP. Superficially projecting principal neurons in layer V of medial entorhinal cortex in the rat receive excitatory retrosplenial input. J Neurosci. 2013 Oct 2;33(40):15779-92

 

Czupryn A, Zhou YD, Chen X, McNay D, Anderson MP, Flier JS, Macklis JD. Transplanted hypothalamic neurons restore leptin signaling and ameliorate obesity in db/db mice. Science. 2011 Nov 25;334(6059):1133-7.

 

Janusz A, Milek J, Perycz M, Pacini L, Bagni C, Kaczmarek L, Dziembowska M. The Fragile X mental retardation protein regulates matrix metalloproteinase 9 mRNA at synapses. J Neurosci. 2013 Nov 13;33(46):18234-41.

 

Kaliszewska A, Bijata M, Kaczmarek L, Kossut M. Experience-dependent plasticity of the barrel cortex in mice observed with 2-DG brain mapping and c-Fos: effects of MMP-9 KO. Cereb Cortex. 2012 Sep;22(9):2160-70.

 

Knapska E, Lioudyno V, Kiryk A, Mikosz M, Górkiewicz T, Michaluk P, Gawlak M, Chaturvedi M, Mochol G, Balcerzyk M, Wojcik DK, Wilczynski GM, Kaczmarek L. Reward learning requires activity of matrix metalloproteinase-9 in the central amygdala. J Neurosci. 2013 Sep 4;33(36):14591-600.

 

Knapska E, Macias M, Mikosz M, Nowak A, Owczarek D, Wawrzyniak M, Pieprzyk M, Cymerman IA, Werka T, Sheng M, Maren S, Jaworski J, Kaczmarek L. Functional anatomy of neural circuits regulating fear and extinction. Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):17093-8

 

Laskowska-Macios K, Zapasnik M, Hu TT, Kossut M, Arckens L, Burnat K. Zif268 mRNA Expression Patterns Reveal a Distinct Impact of Early Pattern Vision Deprivation on the Development of Primary Visual Cortical Areas in the Cat. Cereb Cortex. 2015 Oct;25(10):3515-26.

 

Pitkänen A, Roivainen R, Lukasiuk K. Development of epilepsy after ischaemic stroke. Lancet Neurol. 2015

 

Radwanska K, Medvedev NI, Pereira GS, Engmann O, Thiede N, Moraes MF, Villers A, Irvine EE, Maunganidze NS, Pyza EM, Ris L, Szymańska M, Lipiński M, Kaczmarek L, Stewart MG, Giese KP. Mechanism for long-term memory formation when synaptic strengthening is impaired. Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18471-5.

 

Stawarski M, Rutkowska-Wlodarczyk I, Zeug A, Bijata M, Madej H, Kaczmarek L, Wlodarczyk J. Genetically encoded FRET-based biosensor for imaging MMP-9 activity. Biomaterials. 2014 Feb;35(5):1402-10.

 

Tang Z, Luo OJ, Li X, Zheng M, Zhu JJ, Szalaj P, Trzaskoma P, Magalska A, Wlodarczyk J, Ruszczycki B, Michalski P, Piecuch E, Wang P, Wang D, Tian SZ, Penrad-Mobayed M, Sachs LM, Ruan X, Wei CL, Liu ET, Wilczynski GM, Plewczynski D, Li G, Ruan Y. CTCF-Mediated Human 3D Genome Architecture Reveals Chromatin Topology for Transcription. Cell. 2015 Dec 17;163(7):1611-27.

 

Topolska-Woś AM, Shell SM, Kilańczyk E, Szczepanowski RH, Chazin WJ, Filipek A. Dimerization and phosphatase activity of calcyclin-binding protein/Siah-1 interacting protein: the influence of oxidative stress. FASEB J. 2015 May;29(5):1711-24.

 

van der Kooij MA, Fantin M, Rejmak E, Grosse J, Zanoletti O, Fournier C, Ganguly K, Kalita K, Kaczmarek L, Sandi C. Role for MMP-9 in stress-induced downregulation of nectin-3 in hippocampal CA1 and associated behavioural alterations. Nat Commun. 2014 Sep 18;5:4995.

 

Walczak A, Szczepankiewicz AA, Ruszczycki B, Magalska A, Zamlynska K, Dzwonek J, Wilczek E, Zybura-Broda K, Rylski M, Malinowska M, Dabrowski M, Szczepinska T, Pawlowski K, Pyskaty M, Wlodarczyk J, Szczerbal I, Switonski M, Cremer M, Wilczynski GM. Novel higher-order epigenetic regulation of the Bdnf gene upon seizures. J Neurosci. 2013 Feb 6;33(6):2507-11.