The MRC Protein Phosphorylation Unit and the SCottish Institute of ceLL Signalling (SCILLS) have merged into the MRC Protein Phosphorylation and Ubiquitylation Unit.
The new Unit will still retain the MRC-PPU brand name. Its scientists will focus on investigating the regulation and function of protein phosphorylation and ubiquitylation networks that are strongly linked to understanding fundamental biology as well as disease. Dario Alessi is the current Director of the MRC-PPU and SCILLS and will direct the new merged Unit.
The MRC Protein Phosphorylation Unit was established by Philip Cohen in 1990 and has grown in size over the years from 2 research groups (Philip Cohen and Tricia Cohen) to around 11 groups in 2013. Many ground-breaking results have been made in Protein Phosphorylation Unit over the last 23 years. Highlights include:
[ulist]
[*]Defining the mechanism by which insulin regulates glycogen synthesis (PI 3-kinase-PDK1-Akt-GSK3-glycogen synthase)
[*]Understanding how growth factors stimulate the MAP kinase cascade (RAF-MEK-ERK-RSK/MSK)
[*]Cloning and characterising most of the critical serine/threonine protein phosphatases and their regulatory subunits
[*]Uncovering many important aspects of the stress activated p38 and JNK signalling pathways including how the upstream and downstream components operate and are regulated
[*]Identification of novel key pathways regulating double stranded break DNA damage repair pathways such as the SLX nuclease complexes, FAM60A and more recently DVC1
[*]Playing a major role in uncovering the key role that 14-3-3 protein phosphate recognition adaptors play in regulating biological responses and identifying >500 interactors of these proteins
[*]Discovery of PDK1 and identification of most of the 24 downstream AGC kinases substrates that PDK1 phosphorylates and activates
[*]Discovery of mechanism by which the LKB1 tumour suppressor kinase is regulated by the STRAD pseudokinase and MO25 and identifying all 14 AMPK family protein kinases that are phosphorylated and activated by LKB1
[*]Discovery of the mechanism by which the WNK family kinases regulate blood pressure via the SPAK/OSR1 protein kinases
[*]Dissecting pathways activated by the innate immune signalling Toll-Like Receptors that induce activation of MAP kinase pathways as well as MSK1. Helping to define the critical roles these pathways play in triggering the production of anti-inflammatory and pro-inflammatory cytokines
[*]Uncovering the first physiological substrate for the Parkinson's disease PINK1 kinase and showing that it functions to activate the PARKIN E3 ubiquitin ligase whose mutation also results in Parkinson's disease
[*]Playing a major role in promoting research into developing specific and potent protein kinase inhibitors by helping characterise two of the prototypic kinase inhibits (PD98059 and SB203580) and establishing kinase profiling as a method to quantify the selectivity of kinase inhibitors. MRC-PPU researchers have played an instrumental role in helping characterise dozens of highly specific kinase inhibitors that have had a major impact on our ability to dissect the physiological functions of signal transduction pathways. This has stimulated Pharmaceutical companies to develop kinase inhibitors and ~20 of these are now approved drugs that have cumulative sales of approaching $20 billion dollars per annum
[*]Setting up the Division of Signal Transduction Therapy Unit (DSTT), which is widely regarded as a model for how academia should interact with industry
[/ulist]
[font=Verdana, Arial, Helvetica, sans-serif][align=justify][size=small]About 8 years ago it started to become clear that reversible protein ubiquitylation was going to rival protein phosphorylation as a mechanism that regulates almost all aspects of biology. Moreover, it was also becoming apparent that there was a tremendous interplay between phosphorylation and ubiquitylation pathways and therefore complimentary approaches were needed to investigate these processes. Moreover there was increasing evidence that disruptions in protein ubiquitylation networks lay at the heart of understanding many human diseases and that there would therefore be increasing interest within the pharmaceutical industry to develop strategies to target the ubiquitin pathway.
To address these issues, Philip Cohen persuaded the Scottish Funding Council (via an election pledge from the Scottish National Party) to provide £10 million to set up SCILLS in 2008. SCILLS has thus far made an excellent start. It has enabled five up and coming junior PIs to set up their lab in this area (Gabriela Alexandru, Arno Alpi, Thimo Kurz, Patrick Pedrioli and Satpal Virdee) and permitted the establishment of a number of talented support teams to generate a critical set of reagents and technology to better study of protein ubiquitylation.
Many exciting research projects have been launched to uncover the role of ubiquitin pathways play in mediating diverse processes of relevance to understanding cancer, innate immune pathways, hypertension and neurodegenerative disorders. The research undertaken by SCILLS has also played a major role in our recent £14.4 million renewal of the DSTT collaboration in July 2012 and in founding a new ubiquitin reagent company called Ubiquigent, which is based in Dundee and commercialises many of our ubiquitin reagents and technologies.
The hope is that integration of research being undertaken in the new merged MRC Protein Phosphorylation and Ubiquitylation Unit will result in tremendous synergies and open up new opportunities to understand how the effects of phosphorylation and ubiquitylation work together to control biological systems. The aim is for the MRC-PPU is to act as a major hub of research for basic and clinical researchers as well as pharmaceutical companies to come together to study protein phosphorylation and ubiquitylation systems.
The merger of SCILLS and the MRC Protein Phosphorylation Unit was marked by a special inaugural lecture by Tony Pawson, OC OOnt CH FRS FRSC (Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Toronto) on Wednesday 27th March 2013. Tony Pawson is one of the leading researchers in cell-signalling field whose work has inspired us and provided a framework of knowledge that has helped reveal how disruptions in signalling pathways cause many diseases including cancer, diabetes and immune disorders.[/size][/align][/font]
The new Unit will still retain the MRC-PPU brand name. Its scientists will focus on investigating the regulation and function of protein phosphorylation and ubiquitylation networks that are strongly linked to understanding fundamental biology as well as disease. Dario Alessi is the current Director of the MRC-PPU and SCILLS and will direct the new merged Unit.
The MRC Protein Phosphorylation Unit was established by Philip Cohen in 1990 and has grown in size over the years from 2 research groups (Philip Cohen and Tricia Cohen) to around 11 groups in 2013. Many ground-breaking results have been made in Protein Phosphorylation Unit over the last 23 years. Highlights include:
[ulist]
[*]Defining the mechanism by which insulin regulates glycogen synthesis (PI 3-kinase-PDK1-Akt-GSK3-glycogen synthase)
[*]Understanding how growth factors stimulate the MAP kinase cascade (RAF-MEK-ERK-RSK/MSK)
[*]Cloning and characterising most of the critical serine/threonine protein phosphatases and their regulatory subunits
[*]Uncovering many important aspects of the stress activated p38 and JNK signalling pathways including how the upstream and downstream components operate and are regulated
[*]Identification of novel key pathways regulating double stranded break DNA damage repair pathways such as the SLX nuclease complexes, FAM60A and more recently DVC1
[*]Playing a major role in uncovering the key role that 14-3-3 protein phosphate recognition adaptors play in regulating biological responses and identifying >500 interactors of these proteins
[*]Discovery of PDK1 and identification of most of the 24 downstream AGC kinases substrates that PDK1 phosphorylates and activates
[*]Discovery of mechanism by which the LKB1 tumour suppressor kinase is regulated by the STRAD pseudokinase and MO25 and identifying all 14 AMPK family protein kinases that are phosphorylated and activated by LKB1
[*]Discovery of the mechanism by which the WNK family kinases regulate blood pressure via the SPAK/OSR1 protein kinases
[*]Dissecting pathways activated by the innate immune signalling Toll-Like Receptors that induce activation of MAP kinase pathways as well as MSK1. Helping to define the critical roles these pathways play in triggering the production of anti-inflammatory and pro-inflammatory cytokines
[*]Uncovering the first physiological substrate for the Parkinson's disease PINK1 kinase and showing that it functions to activate the PARKIN E3 ubiquitin ligase whose mutation also results in Parkinson's disease
[*]Playing a major role in promoting research into developing specific and potent protein kinase inhibitors by helping characterise two of the prototypic kinase inhibits (PD98059 and SB203580) and establishing kinase profiling as a method to quantify the selectivity of kinase inhibitors. MRC-PPU researchers have played an instrumental role in helping characterise dozens of highly specific kinase inhibitors that have had a major impact on our ability to dissect the physiological functions of signal transduction pathways. This has stimulated Pharmaceutical companies to develop kinase inhibitors and ~20 of these are now approved drugs that have cumulative sales of approaching $20 billion dollars per annum
[*]Setting up the Division of Signal Transduction Therapy Unit (DSTT), which is widely regarded as a model for how academia should interact with industry
[/ulist]
[font=Verdana, Arial, Helvetica, sans-serif][align=justify][size=small]About 8 years ago it started to become clear that reversible protein ubiquitylation was going to rival protein phosphorylation as a mechanism that regulates almost all aspects of biology. Moreover, it was also becoming apparent that there was a tremendous interplay between phosphorylation and ubiquitylation pathways and therefore complimentary approaches were needed to investigate these processes. Moreover there was increasing evidence that disruptions in protein ubiquitylation networks lay at the heart of understanding many human diseases and that there would therefore be increasing interest within the pharmaceutical industry to develop strategies to target the ubiquitin pathway.
To address these issues, Philip Cohen persuaded the Scottish Funding Council (via an election pledge from the Scottish National Party) to provide £10 million to set up SCILLS in 2008. SCILLS has thus far made an excellent start. It has enabled five up and coming junior PIs to set up their lab in this area (Gabriela Alexandru, Arno Alpi, Thimo Kurz, Patrick Pedrioli and Satpal Virdee) and permitted the establishment of a number of talented support teams to generate a critical set of reagents and technology to better study of protein ubiquitylation.
Many exciting research projects have been launched to uncover the role of ubiquitin pathways play in mediating diverse processes of relevance to understanding cancer, innate immune pathways, hypertension and neurodegenerative disorders. The research undertaken by SCILLS has also played a major role in our recent £14.4 million renewal of the DSTT collaboration in July 2012 and in founding a new ubiquitin reagent company called Ubiquigent, which is based in Dundee and commercialises many of our ubiquitin reagents and technologies.
The hope is that integration of research being undertaken in the new merged MRC Protein Phosphorylation and Ubiquitylation Unit will result in tremendous synergies and open up new opportunities to understand how the effects of phosphorylation and ubiquitylation work together to control biological systems. The aim is for the MRC-PPU is to act as a major hub of research for basic and clinical researchers as well as pharmaceutical companies to come together to study protein phosphorylation and ubiquitylation systems.
The merger of SCILLS and the MRC Protein Phosphorylation Unit was marked by a special inaugural lecture by Tony Pawson, OC OOnt CH FRS FRSC (Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Toronto) on Wednesday 27th March 2013. Tony Pawson is one of the leading researchers in cell-signalling field whose work has inspired us and provided a framework of knowledge that has helped reveal how disruptions in signalling pathways cause many diseases including cancer, diabetes and immune disorders.[/size][/align][/font]