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Hire Dr. Patrick Y.

Sweden

USD 27 /hr

Science writer focus on Molecular Biology and Biotechnology

Profile Summary

10+ years group leader and online Biology textbook writer

Subject Matter Expertise

• ☆ Evolutionary Biology
• ☆ Microbiology
• ☆ Microbiome Research
• ☆ Virology
• ☆ Molecular Virology
• ☆ Molecular Biology
• ☆ Microarrays
• ☆ Molecular Evolution
• ☆ PCR
• ☆ Molecular Cloning
• ☆ DNA Sequencing
• ☆ Gene Expression Analysis
• ☆ Mutagenesis
• ☆ Recombinant DNA
• ☆ RNA Synthesis
• ☆ RNA Sequencing
• ☆ Plasmid DNA
• ☆ DNA Damage & Repair
• ☆ Monoclonal Antibody Production
• ☆ Cell Biology
• ☆ Cell-Based Assays
• ☆ Gene Regulation
• ☆ Biophysics
• ☆ Cell Culture
• ☆ Blotting
• ☆ Athletic Training & Coaching

Services

• Writing

Writing Clinical Trial Documentation, Medical Writing, Non-Medical Regulatory Writing, Technical Writing, Business & Legal Writing, Copywriting, Creative Writing

Work Experience

Group leader

Stockholm University

July 1998 - Present

Docent Molecular Biologist

Stockholm University

July 1998 - December 2010

Education

Biochemistry Biophysics

Oregon State University

October 1988 - June 1992

Certifications

• Qualified High School Science Teacher

  Swedish Education System Skolverket

  January 2020 - Present

Publications

JOURNAL ARTICLE

Young, Patrick, Giovannucci, Tatiana A, Salomons, Florian A, Haraldsson, Martin, Elfman, Lotta H M, Wickström, Malin, Lundbäck, Thomas, Eirich, Jürgen, Altun, Mikael, Jafari, Rozbeh, et al.(2021). Inhibition of the ubiquitin-proteasome system by an NQO1-activatable compound . Cell death & disease.

Basic leucine zipper protein Cnc-C is a substrate and transcriptional regulator of the Drosophila 26S proteasome @article{PMID:21149573,Title={Basic leucine zipper protein Cnc-C is a substrate and transcriptional regulator of the Drosophila 26S proteasome},Author={Grimberg, Kristian Björk and Beskow, Anne and Lundin, Daniel and Davis, Monica M and Young, Patrick},DOI={10.1128/mcb.00799-10},Number={4},Volume={31},Month={February},Year={2011},Journal={Molecular and cellular biology},ISSN={0270-7306},Pages={897—909},Abstract={While the 26S proteasome is a key proteolytic complex, little is known about how proteasome levels are maintained in higher eukaryotic cells. Here we describe an RNA interference (RNAi) screen of Drosophila melanogaster that was used to identify transcription factors that may play a role in maintaining levels of the 26S proteasome. We used an RNAi library against 993 Drosophila transcription factor genes to identify genes whose suppression in Schneider 2 cells stabilized a ubiquitin-green fluorescent protein reporter protein. This screen identified Cnc (cap 'n' collar [CNC]; basic region leucine zipper) as a candidate transcriptional regulator of proteasome component expression. In fact, 20S proteasome activity was reduced in cells depleted of cnc. Immunoblot assays against proteasome components revealed a general decline in both 19S regulatory complex and 20S proteasome subunits after RNAi depletion of this transcription factor. Transcript-specific silencing revealed that the longest of the seven transcripts for the cnc gene, cnc-C, was needed for proteasome and p97 ATPase production. Quantitative reverse transcription-PCR confirmed the role of Cnc-C in activation of transcription of genes encoding proteasome components. Expression of a V5-His-tagged form of Cnc-C revealed that the transcription factor is itself a proteasome substrate that is stabilized when the proteasome is inhibited. We propose that this single cnc gene in Drosophila resembles the ancestral gene family of mammalian nuclear factor erythroid-derived 2-related transcription factors, which are essential in regulating oxidative stress and proteolysis.},URL={https://europepmc.org/articles/PMC3028647}} . Molecular and cellular biology.

Transcription factor Nrf1 mediates the proteasome recovery pathway after proteasome inhibition in mammalian cells @article{PMID:20385086,Title={Transcription factor Nrf1 mediates the proteasome recovery pathway after proteasome inhibition in mammalian cells},Author={Radhakrishnan, Senthil K and Lee, Candy S and Young, Patrick and Beskow, Anne and Chan, Jefferson Y and Deshaies, Raymond J},DOI={10.1016/j.molcel.2010.02.029},Number={1},Volume={38},Month={April},Year={2010},Journal={Molecular cell},ISSN={1097-2765},Pages={17—28},Abstract={In Saccharomyces cerevisiae, chemical or genetic inhibition of proteasome activity induces new proteasome synthesis promoted by the transcription factor RPN4. This ensures that proteasome activity is matched to demand. This transcriptional feedback loop is conserved in mammals, but its molecular basis is not understood. Here, we report that nuclear factor erythroid-derived 2-related factor 1 (Nrf1), a transcription factor of the cap "n" collar basic leucine zipper family, but not the related Nrf2, is necessary for induced proteasome gene transcription in mouse embryonic fibroblasts (MEFs). Promoter-reporter assays revealed the importance of antioxidant response elements in Nrf1-mediated upregulation of proteasome subunit genes. Nrf1(-/-) MEFs were impaired in the recovery of proteasome activity after transient treatment with the covalent proteasome inhibitor YU101, and knockdown of Nrf1 in human cancer cells enhanced cell killing by YU101. Taken together, our results suggest that Nrf1-mediated proteasome homeostasis could be an attractive target for therapeutic intervention in cancer.},URL={https://europepmc.org/articles/PMC2874685}} . Molecular cell.

A conserved unfoldase activity for the p97 AAA-ATPase in proteasomal degradation @article{PMID:19782090,Title={A conserved unfoldase activity for the p97 AAA-ATPase in proteasomal degradation},Author={Beskow, Anne and Grimberg, Kristian Björk and Bott, Laura C and Salomons, Florian A and Dantuma, Nico P and Young, Patrick},DOI={10.1016/j.jmb.2009.09.050},Number={4},Volume={394},Month={December},Year={2009},Journal={Journal of molecular biology},ISSN={0022-2836},Pages={732—746},Abstract={The multifunctional AAA-ATPase p97 is one of the most abundant and conserved proteins in eukaryotic cells. The p97/Npl4/Ufd1 complex dislocates proteins that fail the protein quality control in the endoplasmic reticulum to the cytosol where they are subject to degradation by the ubiquitin/proteasome system. Substrate dislocation depends on the unfoldase activity of p97. Interestingly, p97 is also involved in the degradation of specific soluble proteasome substrates but the exact mode of action of p97 in this process is unclear. Here, we show that both the central pore and ATPase activity of p97 are necessary for the degradation of cytosolic ubiquitin-fusion substrates. Addition of a flexible extended C-terminal peptide to the substrate relieves the requirement for p97. Deletion mapping reveals a conserved length dependency of 20 residues for the peptide, which allows p97-independent degradation to occur. Our results suggest that initiation of unfolding may be more complex than previously anticipated and that the 19S regulatory complex of the proteasome can require preprocessing of highly folded, ubiquitylated substrates by the p97(Ufd1/Npl4) complex. Our data provide an explanation for the observation that p97 is only essential for a subpopulation of soluble substrates and predict that a common characteristic of soluble p97-dependent substrates is the lack of an initiation site to facilitate unfolding by the 26S proteasome.},URL={https://doi.org/10.1016/j.jmb.2009.09.050}} . Journal of molecular biology.

Characterization of a REG/PA28 proteasome activator homolog in Dictyostelium discoideum indicates that the ubiquitin- and ATP-independent REGgamma proteasome is an ancient nuclear protease @article{PMID:19411624,Title={Characterization of a REG/PA28 proteasome activator homolog in Dictyostelium discoideum indicates that the ubiquitin- and ATP-independent REGgamma proteasome is an ancient nuclear protease},Author={Masson, Patrick and Lundin, Daniel and Söderbom, Fredrik and Young, Patrick},DOI={10.1128/ec.00165-08},Number={6},Volume={8},Month={June},Year={2009},Journal={Eukaryotic cell},ISSN={1535-9778},Pages={844—851},Abstract={The nuclear proteasome activator REGgamma/PA28gamma is an ATP- and ubiquitin-independent activator of the 20S proteasome and has been proposed to degrade and thereby regulate both a key human oncogene, encoding the coactivator SRC-3/AIB1, and the cyclin-dependent kinase inhibitor p21 (Waf/Cip1). We report the identification and characterization of a PA28/REG homolog in Dictyostelium. Association of a recombinant Dictyostelium REG with the purified Dictyostelium 20S proteasome led to the preferential stimulation of the trypsin-like proteasome peptidase activity. Immunolocalization studies demonstrated that the proteasome activator is localized to the nucleus and is present in growing as well as starving Dictyostelium cells. Our results indicate that the Dictyostelium PA28/REG activator can stimulate both the trypsin-like and chymotrypsin-like activities of the 20S proteasome and supports the idea that the REGgamma-20S proteasome represents an early unique nuclear degradation pathway for eukaryotic cells.},URL={https://europepmc.org/articles/PMC2698304}} . Eukaryotic cell.

Studies on the role of NonA in mRNA biogenesis @article{PMID:16750525,Title={Studies on the role of NonA in mRNA biogenesis},Author={Kozlova, Natalia and Braga, José and Lundgren, Josefin and Rino, José and Young, Patrick and Carmo-Fonseca, Maria and Visa, Neus},DOI={10.1016/j.yexcr.2006.04.013},Number={13},Volume={312},Month={August},Year={2006},Journal={Experimental cell research},ISSN={0014-4827},Pages={2619—2630},Abstract={The NonA protein of Drosophila melanogaster is an abundant nuclear protein that belongs to the DBHS (Drosophila behavior, human splicing) protein family. The DBHS proteins bind both DNA and RNA in vitro and have been involved in different aspects of gene expression, including pre-mRNA splicing, transcription regulation and nuclear retention of mRNA. We have used double-stranded RNA interference in Drosophila S2 cells to silence the expression of NonA and to investigate its role in mRNA biogenesis. We show that knockdown of NonA does not affect transcription nor splicing. We demonstrate that NonA forms a complex with the essential nuclear export factor NXF1 in an RNA-dependent manner. We have constructed stable S2 cell lines that express full-length and truncated NXF1 fused to GFP in order to perform fluorescence recovery after photobleaching experiments. We show that knockdown of NonA reduces the intranuclear mobility of NXF1-GFP associated with poly(A)(+) RNA in vivo, while the mobility of the truncated NXF1-GFP that does not bind RNA is not affected. Our data suggest that NonA facilitates the intranuclear mobility of mRNP particles.},URL={https://doi.org/10.1016/j.yexcr.2006.04.013}} . Experimental cell research.

Identification and characterization of a Drosophila proteasome regulatory network @article{PMID:15899868,Title={Identification and characterization of a Drosophila proteasome regulatory network},Author={Lundgren, Josefin and Masson, Patrick and Mirzaei, Zahra and Young, Patrick},DOI={10.1128/mcb.25.11.4662-4675.2005},Number={11},Volume={25},Month={June},Year={2005},Journal={Molecular and cellular biology},ISSN={0270-7306},Pages={4662—4675},Abstract={Maintaining adequate proteasomal proteolytic activity is essential for eukaryotic cells. For metazoan cells, little is known about the composition of genes that are regulated in the proteasome network or the mechanisms that modulate the levels of proteasome genes. Previously, two distinct treatments have been observed to induce 26S proteasome levels in Drosophila melanogaster cell lines, RNA interference (RNAi)-mediated inhibition of the 26S proteasome subunit Rpn10/S5a and suppression of proteasome activity through treatment with active-site inhibitors. We have carried out genome array profiles from cells with decreased Rpn10/S5a levels using RNAi or from cells treated with proteasome inhibitor MG132 and have thereby identified candidate genes that are regulated as part of a metazoan proteasome network. The profiles reveal that the majority of genes that were identified to be under the control of the regulatory network consisted of 26S proteasome subunits. The 26S proteasome genes, including three new subunits, Ubp6p, Uch-L3, and Sem1p, were found to be up-regulated. A number of genes known to have proteasome-related functions, including Rad23, isopeptidase T, sequestosome, and the genes for the segregase complex TER94/VCP-Ufd1-Npl4 were also found to be up-regulated. RNAi-mediated inhibition against the segregase complex genes demonstrated pronounced stabilization of proteasome substrates throughout the Drosophila cell. Finally, transcriptional reporter assays and deletion mapping studies in Drosophila demonstrate that proteasome mRNA induction is dependent upon the 5' untranslated regions (UTRs). Transfer of the 5' UTR from the proteasome subunit Rpn1/S2 to a noninducible promoter was sufficient to confer transcriptional upregulation of the reporter mRNA after proteasome inhibition.},URL={https://europepmc.org/articles/PMC1140619}} . Molecular and cellular biology.

Use of RNA interference and complementation to study the function of the Drosophila and human 26S proteasome subunit S13 @article{PMID:12861018,Title={Use of RNA interference and complementation to study the function of the Drosophila and human 26S proteasome subunit S13},Author={Lundgren, Josefin and Masson, Patrick and Realini, Claudio A and Young, Patrick},DOI={10.1128/mcb.23.15.5320-5330.2003},Number={15},Volume={23},Month={August},Year={2003},Journal={Molecular and cellular biology},ISSN={0270-7306},Pages={5320—5330},Abstract={The S13 subunit (also called Pad1, Rpn11, and MPR1) is a component of the 19S complex, a regulatory complex essential for the ubiquitin-dependent proteolytic activity of the 26S proteasome. To address the functional role of S13, we combined double-stranded RNA interference (RNAi) against the Drosophila proteasome subunit DmS13 with expression of wild-type and mutant forms of the homologous human gene, HS13. These studies show that DmS13 is essential for 26S function. Loss of the S13 subunit in metazoan cells leads to increased levels of ubiquitin conjugates, cell cycle defects, DNA overreplication, and apoptosis. In vivo assays using short-lived proteasome substrates confirmed that the 26S ubiquitin-dependent degradation pathway is compromised in S13-depleted cells. In complementation experiments using Drosophila cell lines expressing HS13, wild-type HS13 was found to fully rescue the knockdown phenotype after DmS13 RNAi treatment, while an HS13 containing mutations (H113A-H115A) in the proposed isopeptidase active site was unable to rescue. A mutation within the conserved MPN/JAMM domain (C120A) abolished the ability of HS13 to rescue the Drosophila cells from apoptosis or DNA overreplication. However, the C120A mutant was found to partially restore normal levels of ubiquitin conjugates. The S13 subunit may possess multiple functions, including a deubiquitinylating activity and distinct activities essential for cell cycle progression that require the conserved C120 residue.},URL={https://europepmc.org/articles/PMC165711}} . Molecular and cellular biology.

Drosophila proteasome regulator REGgamma: transcriptional activation by DNA replication-related factor DREF and evidence for a role in cell cycle progression @article{PMID:12662925,Title={Drosophila proteasome regulator REGgamma: transcriptional activation by DNA replication-related factor DREF and evidence for a role in cell cycle progression},Author={Masson, Patrick and Lundgren, Josefin and Young, Patrick},DOI={10.1016/s0022-2836(03)00188-8},Number={5},Volume={327},Month={April},Year={2003},Journal={Journal of molecular biology},ISSN={0022-2836},Pages={1001—1012},Abstract={The proteasome regulator REG (PA28gamma) is a conserved complex present in metazoan nuclei and is able to stimulate the trypsin-like activity of the proteasome in a non-ATP dependent manner. However, the in vivo function for REGgamma in metazoan cells is currently unknown. To understand the role of Drosophila REGgamma we have attempted to identify the type of promoter elements regulating its transcription. Mapping the site of the transcription initiation revealed a TATA-less promoter, and a sequence search identified elements found typically in Drosophila genes involved in cell cycle progression and DNA replication. In order to test the relevance of the motifs, REGgamma transcriptional assays were carried out with mutations in the proposed promoter. Our results indicate that a single Drosophila replication-related element sequence, DRE, is essential for REGgamma transcription. To confirm that REGgamma has a role in cell cycle progression, the effect of removing REGgamma from S2 cells was tested using RNA interference. Drosophila cells depleted of REGgamma showed partial arrests in G1/S cell cycle transition. Immuno-staining of Drosophila embryos revealed that REGgamma is typically localized to the nucleus during embryogenesis with increased levels present in invaginating cells during gastrulation. The REGgamma was found dispersed throughout the cell volume within mitotic domains undergoing cell division. Finally, database searches suggest that the DRE system may regulate key members of the proteasome system in Drosophila.},URL={https://doi.org/10.1016/s0022-2836(03)00188-8}} . Journal of molecular biology.