Jay Gopalakrishnan - JRG IX

Mechanisms and regulation of centrosome biogenesis

Historically, centrosomes have been known to be essential for cilia formation and accurate cell division. At their core, centrosomes are composed of a pair of centrioles surrounded by an amorphous Peri-Centriolar Material (PCM) formed by various multi-protein complexes.

The centriole templates cilia formation during interphase, while the PCM assembles spindle poles during mitosis to nucleate astral and spindle microtubules (MT asters). Thus, centrosomes are critical for animal development and their dysfunction results in many developmental disorders.

In addition, nearly all types of cancer cells have abnormal numbers of centrosomes and the abnormal number of centrosomes has a direct correlation to chromosomal instability during tumor formation.

This implicates that not only the functionality but also the correct number of centrosomes is crucial for the viability of organisms. Thus, it is very important for biology and medical science to understand the regulatory mechanisms of centrosome biogenesis.

To this end, we aim to elucidate the fundamental principles of centrosome biogenesis to uncover how their dysfunctions can lead to developmental disorders, genomic instability, cancer and diseases associated with aging.

Currently, our studies are concentrated in the following topics using an ideal model organism, fruit fly. We develop a robust system using fruit fly where genetic and biochemical strategies are applied together to study centrosome biogenesis both in vivo and in vitro.

Selected publications 2018

Martinez Carrera LA, Gabriel E, Donohoe CD, Holker I, Mariappan A, Storbeck M, Uhlirova M, Gopalakrishnan J, and Wirth B (2018). Novel insights into SMALED2: BICD2 mutations increase microtubule stability and cause defects in axonal and NMJ development. Hum Mol Genet 27, 1772-1784.

Selected publications 2017

Gabriel E, and Gopalakrishnan J (2017). Generation of iPSC-derived human brain organoids to model early neurodevelopmental disorders. J Vis Exp 122, DOI: 10.3791/55372.
 
Gabriel E, Ramani A, Karow U, Gottardo M, Natarajan K, Gooi LM, Goranci-Buzhala G, Krut O, Peters F, Nikolic M, Kuivanen S, Korhonen E, Smura T, Vapalahti O, Papantonis A, Schmidt-Chanasit J, Riparbelli M, Callaini G, Kronke M, Utermohlen O, and Gopalakrishnan J (2017). Recent Zika virus isolates induce premature differentiation of neural progenitors in human brain organoids. Cell Stem Cell 20, 397-406 e395.
 
Goranci-Buzhala G, Gabriel E, Mariappan A, and Gopalakrishnan J (2017). Losers of primary Cilia gain the benefit of survival. Cancer Discov 7, 1374-1375.

Selected publications 2016

Brenke JK, Salmina ES, Ringelstetter L, Dornauer S, Kuzikov M, Rothenaigner I, Schorpp K, Giehler F, Gopalakrishnan J, Kieser A, Gul S, Tetko IV, and Hadian K (2016). Identification of small-molecule frequent hitters of glutathione s-transferase-glutathione interaction. J Biomol Screen 10.1177/1087057116639992.

Gabriel E, Wason A, Ramani A, Gooi LM, Keller P, Pozniakovsky A, Poser I, Noack F, Telugu NS, Calegari F, Saric T, Hescheler J, Hyman AA, Gottardo M, Callaini G, Alkuraya FS, and Gopalakrishnan J (2016). Cpap promotes timely cilium disassembly to maintain neural progenitor pool. EMBO J 35, 803-819.

Thomopoulou P, Sachs J, Teusch N, Mariappan A, Gopalakrishnan J, and Schmalz HG (2016). New colchicine-derived triazoles and their influence on cytotoxicity and microtubule morphology. ACS Med Chem Lett 7, 188-191.

Wike CL, Graves HK, Wason A, Hawkins R, Gopalakrishnan J, Schumacher J, and Tyler JK (2016). Excess free histone h3 localizes to centrosomes for proteasome-mediated degradation during mitosis in metazoans. Cell Cycle 10.1080/15384101.2016.1192728, 1-10.

Zheng X, Ramani A, Soni K, Gottardo M, Zheng S, Ming Gooi L, Li W, Feng S, Mariappan A, Wason A, Widlund P, Pozniakovsky A, Poser I, Deng H, Ou G, Riparbelli M, Giuliano C, Hyman AA, Sattler M, Gopalakrishnan J, and Li H (2016). Molecular basis for cpap-tubulin interaction in controlling centriolar and ciliary length. Nat Commun 7, 11874.

Selected publications 2014

Pannu V, Rida PC, Celik B, Turaga RC, Ogden A, Cantuaria G, Gopalakrishnan J, and Aneja R (2014). Centrosome-declustering drugs mediate a two-pronged attack on interphase and mitosis in supercentrosomal cancer cells. Cell death & disease 5, e1538.

Schorpp K, Rothenaigner I, Salmina E, Reinshagen J, Low T, Brenke JK, Gopalakrishnan J, Tetko IV, Gul S, and Hadian K (2014). Identification of small-molecule frequent hitters from alphascreen high-throughput screens. J Biomol Screen 19, 715-726.

Zheng X, Gooi LM, Wason A, Gabriel E, Mehrjardi NZ, Yang Q, Zhang X, Debec A, Basiri ML, Avidor-Reiss T, Pozniakovsky A, Poser I, Saric T, Hyman AA, Li H, and Gopalakrishnan J (2014). Conserved tcp domain of sas-4/cpap is essential for pericentriolar material tethering during centrosome biogenesis. Proc Natl Acad Sci U S A 111, E354-363.

Selected publications 2013

Avidor-Reiss T, and Gopalakrishnan J (2013). Building a centriole. Curr Opin Cell Biol 25, 72-77.
 
Avidor-Reiss T, and Gopalakrishnan J (2013). Cell cycle Regulation of the centrosome and cilium. Drug Discov Today Dis Mech 10, e119-e124


Dr. Jay Gopalakrishnan

Center for Molecular Medicine Cologne

Dr. Jay Gopalakrishnan

Principal Investigator - CMMC-JRG IX
Head - Microscopy Unit

jay.gopalakrishnan@uni-koeln.de

Work +49 221 478 89691

CMMC Research Building
Robert-Koch-Str. 21
50931 Cologne

http://centrosome-cilia-lab.com/

Gopalakrishnan´s Webpage

http://centrosome-cilia-lab.com/

Publications - Jay Gopalakrishnan

Link to PubMed