@phdthesis{discovery1561240,
          school = {UCL (University College London)},
           month = {July},
            note = {Unpublished},
       booktitle = {UCL (University College London)},
            year = {2017},
           title = {Lysosome-related organelles: an investigation into clinical disorders of endothelial cells and platelets},
             url = {https://discovery.ucl.ac.uk/id/eprint/1561240/},
        abstract = {Lysosome-related	 organelles	 (LROs)	 are	 a	 heterogeneous group	 of	 organelles	
that	have	important	functions	in	a	number	of	specialised	cell	types.	LROs,	despite	
their	distinct	 features	and	morphology,	have	been	grouped	 together	due	 to	 the	
observation	 that	 they	 are	 simultaneously	 functionally	 perturbed by	 single	
mutations	in	a	number	of	genetic	disorders,	yet	as	a	group	they	are	still	poorly	
understood.	
Firstly,	 it	 was investigated	 whether	 the	 genes	 that	 are	 important	 for	 the	
formation/maturation	 of	 other	 LROs	 can	 also	 affect	 Weibel-Palade	 bodies	
(WPBs)	an	endothelial	 LRO	 that	is	 critical	 to	 haemostasis	and	inflammation.	 In	
the	genetic	disorder	Hermansky	Pudlak syndrome	(HPS)	a	number	of	LROs	are	
affected,	but	the	effect	of	these	mutations	on	WPBs	is	not	yet	established.	It	was
investigated	 whether	 these	 genes	 are	 indeed	 important	 for	 the	 biogenesis	 and	
function	 of	WPBs,	 potentially	 revealing	a	 new	aspect	 of	 the	 disease	 phenotype.	
siRNA	ablation	in	human	endothelial	cells	of	genes	identified	as	involved	in	LRO	
biogenesis	 proved	 to	 give	 inconclusive results	 as	 to	 their	 importance	 in	 WPB	
formation	and	function.	
Secondly,	the understanding	of	LRO-related	genetic	disorders would	be	aided	by	
an	 improvement	 in diagnostics.	 The	 diagnosis	 of	 platelet	 storage	 disorders	
(PSDs) is	 currently	 limited	 to	 the	 observation	 of	 symptoms	 (e.g.	 a	 bleeding	
disorder	or	albinism)	 that	are	often	shared	with	other,	more	common	diseases.	
Most	 HPS	 patients	 are	 initially	 misdiagnosed and	 many	 see	 4	 to	 6	 specialists	
before	 being	 correctly	 identified.	 I	 investigated	 whether	 Super	 Resolution	
Microscopy,	 allowing	 images	 to	 be	 taken	 with	 a	 higher	 resolution	 than	
the diffraction	limit	 ({\ensuremath{<}}200 nm),	 has	 the	 potential	 for	improving	 the	imaging	 of	
platelet	granules	and	thereby	the	diagnosis	and	characterisation	of	LRO-related	
disorders.	 The	 use	 of	 structured	 illumination	 microscopy,	 coupled	 with	automated	 image	 analysis	 bioinformatics	 allowed	 for	 a	 highly	 efficient	
differentiation	between	control	and	patient	platelets.},
          author = {Westmoreland, DA}
}