Overview
I’m a student under dual supervision of Dr Benjamin Housden and Dr James Wakefield. My research focuses on studying the roles of Polo kinase during cell division. I am using the variable dose analysis screening method developed by Dr Housden to determine functional interactors of Polo to further our understanding of the complex machinery that controls cell division.
I completed my ScB degree in Biochemistry and Molecular Biology at Brown University. Within my first few weeks there I joined the laboratory of Dr. Robert Reenan where I completed an independent project using the TALEN genetic editing technology under the guidance of Dr. Leila Rieder, then a fifth year graduate student.
Post matriculation, I expanded my research toolbox at the Drosophila RNAi Screening Center (DRSC), a functional genomics platform at Harvard Medical School, which provides bioinformatics and cell-based and in vivo screening support to the Drosophila community. The DRSC was founded by Prof. Norbert Perrimon and retains a very close working relationship with his lab. As a research assistant, I split my time between generating reagents for cell-based screens for outside researchers and assisting in collaborations with post-doctoral fellows in the Perrimon lab.
Research group links
Research
Research interests
I am currently investigating physical interactors of Polo kinase.
Publications
Variable Dose Analysis: A Novel High-throughput RNAi Screening Method for Drosophila Cells. Sierzputowska K, Baxter CR, and Housden BE. Bio-protocol 8(24): e3112. DOI: 10.21769/BioProtoc.3112.
Zinc Detoxification: A Functional Genomics and Transcriptomics Analysis in Drosophila melanogaster Cultured Cells. Mohr SE, Rudd K, Hu Y, Song WR, Gilly Q, Buckner M, Housden BE, Kelley C, Zirin J, Tao R, Amador G, Sierzputowska K, Comjean A, Perrimon N. G3 (Bethesda). 2018 Feb 2;8(2):631-641. doi: 10.1534/g3.117.300447.
Reagent and Data Resources for Investigation of RNA Binding Protein Functions in Drosophila melanogaster Cultured Cells. Mohr SE, Hu Y, Rudd K, Buckner M, Gilly Q, Foster B, Sierzputowska K, Comjean A, Ye B, Perrimon N. G3 (Bethesda). 2015 Jul 21;5(9):1919-24. doi: 10.1534/g3.115.019364.
Presentations
- April 2018 SW Fly Meeting, Bristol, UK
- May 2018 ExeBioCon
- February 2019 HBIGS Winter School ''Molecular mechanisms in mitosis''
- March 2019 ADRC 2019, Dallas, TX
Society Memberships
Publications
Key publications | Publications by category | Publications by year
Publications by category
Journal articles
Sierzputowska K, Baxter CR, Housden BE (2018). Variable Dose Analysis: a Novel High-throughput RNAi Screening Method for Drosophila Cells. Bio-protocol, 8(24).
Mohr SE, Rudd K, Hu Y, Song WR, Gilly Q, Buckner M, Housden BE, Kelley C, Zirin J, Tao R, et al (2018). Zinc Detoxification: a Functional Genomics and Transcriptomics Analysis in Drosophila melanogaster Cultured Cells.
G3 (Bethesda),
8(2), 631-641.
Abstract:
Zinc Detoxification: a Functional Genomics and Transcriptomics Analysis in Drosophila melanogaster Cultured Cells.
Cells require some metals, such as zinc and manganese, but excess levels of these metals can be toxic. As a result, cells have evolved complex mechanisms for maintaining metal homeostasis and surviving metal intoxication. Here, we present the results of a large-scale functional genomic screen in Drosophila cultured cells for modifiers of zinc chloride toxicity, together with transcriptomics data for wild-type or genetically zinc-sensitized cells challenged with mild zinc chloride supplementation. Altogether, we identified 47 genes for which knockdown conferred sensitivity or resistance to toxic zinc or manganese chloride treatment, and >1800 putative zinc-responsive genes. Analysis of the 'omics data points to the relevance of ion transporters, glutathione (GSH)-related factors, and conserved disease-associated genes in zinc detoxification. Specific genes identified in the zinc screen include orthologs of human disease-associated genes CTNS, PTPRN (also known as IA-2), and ATP13A2 (also known as PARK9). We show that knockdown of red dog mine (rdog; CG11897), a candidate zinc detoxification gene encoding an ABCC-type transporter family protein related to yeast cadmium factor (YCF1), confers sensitivity to zinc intoxication in cultured cells, and that rdog is transcriptionally upregulated in response to zinc stress. As there are many links between the biology of zinc and other metals and human health, the 'omics data sets presented here provide a resource that will allow researchers to explore metal biology in the context of diverse health-relevant processes.
Abstract.
Author URL.
Mohr SE, Hu Y, Rudd K, Buckner M, Gilly Q, Foster B, Sierzputowska K, Comjean A, Ye B, Perrimon N, et al (2015). Reagent and Data Resources for Investigation of RNA Binding Protein Functions in Drosophila melanogaster Cultured Cells.
G3-GENES GENOMES GENETICS,
5(9), 1919-1924.
Author URL.
Publications by year
2022
Sierzputowska K (2022). An integrated analysis of the protein-protein interaction network of the conserved mitotic kinase, Polo.
Abstract:
An integrated analysis of the protein-protein interaction network of the conserved mitotic kinase, Polo
Polo kinase, first identified in Drosophila over 30 years ago, is a highly conserved
enzyme that functions pleiotropically during multiple stages of cell division. Members
of this protein family have crucial roles in cell cycle progression, centriole duplication,
mitosis, cytokinesis and the DNA damage response. Although some Polo substrates
and regulatory mechanisms have been identified, we still lack complete
understanding of the cellular and molecular roles of this kinase. Previous work in the
Wakefield lab identified 40 proteins that physically interact with Polo in Drosophila
embryos, but the functional significance of these components remains unknown. As
genetic interaction screening can identify functional relationships between genes, I
performed a highly sensitive assay called Variable Dose Analysis (VDA) in
Drosophila S2R+ cells to determine which of the physical interactors also have
genetic interactions with Polo. Inhibiting Polo using the selective small-molecule
inhibitor BI-2536 and transfecting shRNA against the genes of interest allowed to
easily screen cells based on their viability phenotype. Known Polo genetic
interactors, Map205 and mtrm, were identified by the VDA screen, validating its
robustness and utility in identifying genetic interactors. Fourteen genes were
selected as hits, with components of the ubiquitination system enriched among them,
particularly all member proteins of the Skp, Cullin, F-box containing complex (SCF
complex). Six candidate polo interactors, SkpA, Cul1, slmb, Ck1α, Klp61F, and cher
were selected for validation and further characterization of the interactions in vivo.
Inhibition of Ck1α and slmb via RNAi resulted in larval lethality. Live imaging of SkpA
RNAi and Cul1 RNAi larvae showed an increase in the cortical localization of poloGFP during late anaphase/telophase. Together, these results suggest that polo may
be degraded in an SCF-dependent manner in Drosophila. Further follow up work is
needed to gain deeper insight into the relationship between the ubiquitination system
and polo.
Abstract.
2018
Sierzputowska K, Baxter CR, Housden BE (2018). Variable Dose Analysis: a Novel High-throughput RNAi Screening Method for Drosophila Cells. Bio-protocol, 8(24).
Mohr SE, Rudd K, Hu Y, Song WR, Gilly Q, Buckner M, Housden BE, Kelley C, Zirin J, Tao R, et al (2018). Zinc Detoxification: a Functional Genomics and Transcriptomics Analysis in Drosophila melanogaster Cultured Cells.
G3 (Bethesda),
8(2), 631-641.
Abstract:
Zinc Detoxification: a Functional Genomics and Transcriptomics Analysis in Drosophila melanogaster Cultured Cells.
Cells require some metals, such as zinc and manganese, but excess levels of these metals can be toxic. As a result, cells have evolved complex mechanisms for maintaining metal homeostasis and surviving metal intoxication. Here, we present the results of a large-scale functional genomic screen in Drosophila cultured cells for modifiers of zinc chloride toxicity, together with transcriptomics data for wild-type or genetically zinc-sensitized cells challenged with mild zinc chloride supplementation. Altogether, we identified 47 genes for which knockdown conferred sensitivity or resistance to toxic zinc or manganese chloride treatment, and >1800 putative zinc-responsive genes. Analysis of the 'omics data points to the relevance of ion transporters, glutathione (GSH)-related factors, and conserved disease-associated genes in zinc detoxification. Specific genes identified in the zinc screen include orthologs of human disease-associated genes CTNS, PTPRN (also known as IA-2), and ATP13A2 (also known as PARK9). We show that knockdown of red dog mine (rdog; CG11897), a candidate zinc detoxification gene encoding an ABCC-type transporter family protein related to yeast cadmium factor (YCF1), confers sensitivity to zinc intoxication in cultured cells, and that rdog is transcriptionally upregulated in response to zinc stress. As there are many links between the biology of zinc and other metals and human health, the 'omics data sets presented here provide a resource that will allow researchers to explore metal biology in the context of diverse health-relevant processes.
Abstract.
Author URL.
2015
Mohr SE, Hu Y, Rudd K, Buckner M, Gilly Q, Foster B, Sierzputowska K, Comjean A, Ye B, Perrimon N, et al (2015). Reagent and Data Resources for Investigation of RNA Binding Protein Functions in Drosophila melanogaster Cultured Cells.
G3-GENES GENOMES GENETICS,
5(9), 1919-1924.
Author URL.
Kasia_Sierzputowska Details from cache as at 2023-01-29 22:44:53
Refresh publications
External Engagement and Impact
Other
Outreach/involvement
- May 2018 Exeter Pint of Science volunteer
- CLESCon 2018 organizing committee
- Graduate Research Student Representative at the Postgraduate Research Liaison Forum (PGRLF)
- BioCon2019 organizing committee
- CLESCon 2019 organizing committee
- Exeter Scholars (summer 2019) demonstrator
Teaching
2018/2019
Fall term
Demonstrator:
- BIO1334 Genetics (MedSci)
- BIO1332 Biochemistry (MedSci)
Spring term:
- Graduate Teaching Assistant BIO1339 Cells