Allie Colaco

Name

Name: Allie Colaco
Nationality: United States of America

University of Oxford,
Department of Pharmacology,
Mansfield Road

Contact details:
alexandria.colaco@pharm.ox.ac.uk,
01865 271874

Biosketch

Allie Colaco was born in Pittsburg, CA, USA, and studied biological sciences at the University of Notre Dame (USA). At the University of Notre Dame, Allie focused on environmental sciences and ecology where she looked at the effect of climate change on shifting temperate forest species from the molecular perspective using ancient DNA. In addition to an interest in ecology, she also gained research experience and gained interest in lipids and lysosomal disorders as an undergraduate working primarily to isolate lipids in a biochemistry lab as well as working in a reproductive science lab on hormone localization in the mice brain.

Allie Colaco will be based at the University of Oxford in Professor Frances Platt’s lab where she will be focused on the neurodegenerative, lysosomal storage disease Niemann-Pick type C. Her SphingoNet project is entitled “ Niemann-Pick type C disease: pathogenesis and therapy”.

Project title:

Niemann-Pick type C disease: pathogenesis and therapy

Project summary:

My project aims to derive the function of the NPC cellular pathway and characterize the cellular and biochemical phenotypes of NPC. This will include examining the role that NPC1 protein plays in sphingoid base efflux from lysosomes and determining what the substrates are for the NPC1 protein. This will be done through functional analysis of the NPC protein and identification of vacuolar sphingoid base transporters in yeast and human cells. Using a NPC yeast model, we will analyze the role of NPC protein in sphingoid base metabolism.

We will also use ergosterol and lipid traffic mutants to dissect regulation of NPC, and employ genetic screens to identify vacuolar sphingoid base transporters. Probes and transporters identified in the yeast model will provide the base for identifying probes/transporters in mouse and patient derived cells. We are also interested in seeing how sphingosine storage affects acidic store calcium filling, and what proteins play a role in the filling of the acidic stores with calcium. Also, to investigate whether sphingomyelin acts as a molecular trap for cholesterol in Niemann-Pick type C, we will inhibit sphingomyelin biosynthesis in patient derived cells and examine the effects.

I am also interested in looking at the connections between NPC and other diseases, such as tangier disease, and using these shared characteristics as a potential therapeutic approach for other diseases.

Supervisors

Frances Platt (University of Oxford, UK)
Howard Riezman (Université de Geneve, Switserland)

Biosketch 1st scientific supervisor:

Professor Frances Platt is a professor of biochemistry and pharmacology at the University of Oxford, and was elected a fellow of the Academy of Medical Sciences in 2011. Her laboratory, based in the department of pharmacology, is focused on understanding and treating lysosomal storage disorders. The majority of lysosomal disorders do not have a specific treatment or therapy, and the lab looks at the cell biology and pathobiology, as well as the development of novel therapies for treating these diseases.

A major focus of the lab is in NPC disease with studies focusing on the pathogenic cascade, biomarker identification and trialing different therapies in mouse models of the disorder.