David M. Glover

PRINCIPAL INVESTIGATOR

Having carried his PhD studying the transcription of the polyoma virus genome in infected mouse fibroblasts in Lionel Crawford’s laboratory in ICRF, London, David was fortunate to participate in the Recombinant DNA revolution at Stanford with David Hogness in the early 1970s. This led to the discovery of sequences that interrupted the ribosomal genes of Drosophila, which was the initial research focus of David Glover’s laboratory, first established at Imperial College, London.

While at Imperial, David was awarded a 10-year personal fellowship from the UK’s Cancer Research Campaign that allowed the lab to open up a new area of research pioneering the use of Drosophila as a model in which to study cell cycle regulation. We began by characterizing the duplication cycles of centrosomes in the rapid nuclear division cycles of Drosophila embryos. This led to genetic studies that discovered and named the Polo and Aurora protein kinases, required for the function of centrosomes at the poles of mitotic spindles.

In 1989, after leaving Imperial to move to the University of Dundee, David’s lab showed that Drosophila Polo kinase was not only required for the mitotic functions of centrosomes but also for cytokinesis. In parallel work on the fission yeast, we identified Polo’s counterpart, Plo1, and showed it too was required to establish functional spindle pole bodies and cytokinetic rings. Remarkably, the localization and function of Polo kinase at the centrosome, the kinetochore and the central spindle in cytokinesis was highly conserved in human cells where its expression was elevated in tumours. This led David to initiate collaborations with Biotech and Pharma to develop small molecule inhibitors of both Polo and Aurora mitotic kinases for use in cancer therapy.

In 1999, David Glover moved to the University of Cambridge to become the 6th Arthur Balfour Professor of Genetics. There, we discovered the second main Aurora B kinase required for cells to progress through metaphase and we used genetic approaches to identify and demonstrate the roles of the Greatwall kinase in inhibiting protein phosphatase 2A during mitotic entry and progression.

Over recent years our lab has focused upon centriole duplication following our demonstration that Polo-like-kinase 4 (Plk4) is its master regulator. Indeed, Plk4 expression is able to drive the de novo formation of centrioles in unfertilized Drosophila eggs that lack any centriolar template. In searching for Plk4’s partners, we identified Asterless (Cep152 in human cells) as required to target Plk4 to centrioles and an F-box protein, Slimb – a component of the SCF ubiquitin protein ligase, as responsible for directing any excess Plk4 for destruction. We demonstrated that Plk4 phosphorylates the centriole protein Ana2/STIL to enable it to bind the “cartwheel protein” Sas6 and thus initiate procentriole formation, the first step of centriole duplication. This led to our current studies on the centriole duplication pathway in Drosophila, human and mouse.

Pallavi Panda

POST-DOC

Pallavi completed her PhD in Genetics at the University of Cambridge, United Kingdom. She studied centrosome biogenesis and function in Drosophila melanogaster using various genetic tools, biochemical approaches, and imaging techniques. Now, she is interested in combining her background in centriole biology to study the role of centrosomes and cilia in early mammalian development using stem cell-based embryo models.

Agota Nagy

POST-DOC

Agota obtained a PhD in Biology from the University of Szeged, Hungary, in 2020. In 2021 she joined the Glover lab as a postdoc. Agota’s research focuses on the centriolar protein Ana1/Cep295 and its interacting partners in Drosophila melanogaster. Ana1 is the central component of a molecular network, extending from the inner to the outer part of the centriole. This network is responsible for the process of centriole to centrosome conversion, enabling the nucleation of microtubules and centriole duplication. Ana1 also plays an essential role in the elongation and maintenance of centrioles. Now, Agota’s using the sophisticated genetic tools available in Drosophila to define the independent functions of Ana1’s domains and their interactions with other key centriolar proteins.

Inês Baião Santos

POST-DOC

Inês completed a BSc in Biomedical Pharmacy, followed by a MSc in Cellular and Molecular Biology, at the University of Coimbra, Portugal. She then received a fellowship to work in the Light Microscopy Facility, at the University of Algarve, where she discovered the fascinating world of visualizing biological processes. Inês pursued a PhD in Biomedical Sciences at the University of Algarve, Portugal, focusing on the mechanisms regulating cell proliferation in eukaryotes. Using a wide range of genetic tools and imaging techniques, she characterized Mob genes and investigated their effects on the modulation of signaling pathways during development. Currently, Inês is a postdoctoral researcher studying the regulation of centriole numbers, and the interplay between DNA and centrosome licensing, aiming to uncover new insights into centriole duplication and potential implications for cancer biology.

Vickie Yang

PhD STUDENT

Vickie did her undergraduate study at Peking University majoring in Biological Science, and is now a graduate student in Biology at Caltech. Vickie’s interests focus on the mechanisms of centriole number control and its relationship with cilia regulation and cell proliferation.

Xieze Xu

PhD STUDENT

Xieze graduated from the Li Ka Shing Faculty of Medicine, University of Hong Kong with the highest GPA among his medical science cohort. During his undergrad, Xieze studied the downstream effector of PI3KR2 under the supervision of Dr Lydia Cheung Wai Ting. Later, he pursued the Master of Philosophy (by research) at the Gurdon Institute, University of Cambridge with Dr Hansong Ma, using a forward genetics screen in Drosophila to identify novel mitochondrial dynamics regulators. During his time at Cambridge, Xieze developed a profound interest in fly work and inter-organelle communication. Xieze is now trying to decode the organelle language using fly models at the Glover lab.

Anthony Gutierrez

PhD STUDENT

Anthony grew up in the Los Angeles area and acquired his Bachelors of Science in Microbiology at California State University – Northridge. He cultivated an interest in genetics and pathology during his undergraduate experiences performing research on bacteria, yeast, and nematodes. As a PhD student, Anthony is interested in how ubiquitin specific peptidases regulate duplication of centrioles and how they may contribute to supernumerary centrioles and tumourigenesis.

Cheryl Yu

PhD STUDENT

Cheryl completed her bachelor’s degree in Chemistry at the University of Michigan, Ann Arbor, followed by a master’s degree in Biochemistry at the University of California, San Diego. She investigated Annexin A7 protein phase separation and fibrillization using biophysical approaches. Her current research focuses on the regulation pathways of centriole duplication and tumorigenesis, as well as the key protein interactions governing centriole assembly and function.