عنوان

Characterising the role of mTORC1 in myeloid cells

شماره

TLets766005

عنوان اصلي

Characterising the role of mTORC1 in myeloid cells

نام عام مواد

[Thesis]

نام نخستين پديدآور

Yamani, Lamya Zohair

نام ناشر، پخش کننده و غيره

Queen Mary University of London

تاریخ نشرو بخش و غیره

2017

جزئيات پايان نامه و نوع درجه آن

Thesis (Ph.D.)

امتياز متن

2017

متن يادداشت

The mammalian target of rapamycin (mTOR) signalling pathway takes part in both extracellular and intracellular signals. It is a major regulator of cell metabolism, growth, proliferation and survival. mTOR also regulates critical processes such as cytoskeletal organization, ribosomal biogenesis, transcription and protein synthesis. The mTOR pathway has been implicated in many diseases such as cancer, neurodegeneration and diabetes, which impact homeostasis and cellular functions. Moreover, mTOR has also been shown to play a critical role in immune cell regulation of T and B cells together with neutrophils and antigen presenting cells, as it integrates signals between them extending to the entire immune microenvironment. The aim of my study was to investigate the role of a component of the mTOR complex 1, Raptor, in myeloid cells. My findings show that the absence of Raptor knock out (KO) does not affect bone marrow derived macrophage (BMDM) differentiation and maturation. However, the absence of Raptor influences BMDM polarisation towards an inflammatory phenotype, at least at the level of transcription as observed by increases in mRNA expression of inflammatory cytokines such as TNFα, IL-12β, and IL-6. This finding was consolidated by an increase in NFκΒ pathway signalling in Raptor KO BMDMs. Downstream intracellular signalling in myeloid cells was affected by deletion of Raptor as I found reduced S6K phosphorylation in Raptor KO BMDMs compared to wild type (WT) BMDMs. As a consequence of Raptor absence in BMDMs, STAT3 phosphorylation was also reduced. Raptor deletion did not impact the PI3K/Akt signalling pathway, but decreased phosphorylation of ERK. BMDMs lacking Raptor had reduced phagocytic activity as they were also observed to migrate less towards a pancreatic cancer cell line. However preliminary experiments in pancreatic cancer models did not indicate a major role for Raptor in the activity of tumour associated myeloid cells. My results demonstrate that Raptor and by implication mTORC1, is involved in macrophage polarisation and function.

موضوع مستند نشده

Cancer and Inflammation ; mammalian target of rapamycin signalling pathway ; myeloid cells ; bone marrow derived macrophage

مستند نام اشخاص تاييد نشده

Yamani, Lamya Zohair

مستند نام تنالگان تاييد نشده

Queen Mary, University of London

نام الکترونيکي

فرمت انتشار

p

نوع ماده

[Thesis]

کد کاربرگه

276903

سطح دسترسي

a

تكميل شده

Y