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 To interested students wishing to apply for Science Without Borders funding: PI name & contact detai ls: Dr. Astri d Sasse Assist. Prof. in Pharmaceutical hemistry !mail sassea"tcd.ie Phone #$%$'()* +),) School: Pharmacy and Pharmaceutical Sciences -esearch entre group a/liation: Trinity Biomedical Sciences Institute 0TBSI1 -esearch group centre we2site: http://www.tcd.ie/biosciences/research/pis- live.php PI we2site lin3 to 4: http://people.tcd.ie/sassea Brief summary of PI research: Astrid Sasse is a registered pharmacist who studies genetic linkage of histamine H4 receptors with various diseases. Dr . Sasse is also the Director of Teaching and Learning (U! in the School of "harmac# and "harmaceutical Sciences at T rinit# $ollege. Title & 2rief description of PhD pro5ect: Analysis of the Promoter of the 6istamine 67 -eceptor 8ene.  The human Histamine H4 %eceptor (hH4%! is the newest mem&er in the histamine receptor famil#' which is primaril# epressed in haematopoietic cells. ) *nterestingl#' the H%H4 gene is characterised &# a microsatellite triplet repeat variation in the promoter region' where this $AA trinucleotide repeat can &e repeated )+ , )- times. The length of this triplet repeat ma# aect receptor epression. %ecent pu&lications focusing on length variations in &oth coding and non/coding region of genes showed &iological importance and association to human diseases' such as in Huntington disease' m#otonic d#stroph# and 0ragile 1 s#ndrome. 2  %epeats in non/coding regions (i.e.' promoter region! can have a signi3cant impact on the gene including generation of chromosome fragilit#' silencing of the gene and modulation of transcription and translation of the protein. 2  Aim of the "hD proect5  The aim of this proect is to generate &# molecular cloning several plasmid vectors which contain varia&le num&ers of triplet repeats (67T%s! within the H4 receptor promoter region in frame to a luciferase reporter gene which will the transfected into cells. The luciferase reporter gene will &e activated &# the H4 promoter which will create a luminescent read/out in transfected cells. %esear ch will also encompass patient D7A samples' where pol#morphism will &e linked to conditions such as childhood atopic dermatitis through colla&oration with 8ur Lad# $hildren9s Hospital' $rumlin in Du&lin. ) :icallef S and Sasse A. " ol#mo rphis ms and ge netic l inkag e of histamine rec eptor s (2+);!. Life Sci. -;()<!54=>/-4. 2 Usdin ? The &io logic al ee cts of s imple t andem r epeat s5 L esso ns fro m the r epea t epansion diseases (2++=!. enome %es. )=5)+)),)+)-. ;

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Dr. Astrid SasseAssist. Prof. in Pharmaceutical Chemistry

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To interested students wishing to apply for Science Without Borders funding:PI name & contact details:

Dr. Astrid SasseAssist. Prof. in Pharmaceutical ChemistryEmail [email protected] +353-1-896 2979

School:

Pharmacy and Pharmaceutical Sciences

Research Centre / group affiliation:

Trinity Biomedical Sciences Institute (TBSI)

Research group / centre website:

http://www.tcd.ie/biosciences/research/pis-live.php

PI website / link to CV:

http://people.tcd.ie/sassea

Brief summary of PI research:Astrid Sasse is a registered pharmacist who studies genetic linkage of histamine H4 receptors with various diseases. Dr. Sasse is also the Director of Teaching and Learning (UG) in the School of Pharmacy and Pharmaceutical Sciences at Trinity College.

Title & brief description of PhD project:

Analysis of the Promoter of the Histamine H4 Receptor Gene.The human Histamine H4 Receptor (hH4R) is the newest member in the histamine receptor family, which is primarily expressed in haematopoietic cells.1 Interestingly, the HRH4 gene is characterised by a microsatellite triplet repeat variation in the promoter region, where this CAA trinucleotide repeat can be repeated 10 19 times. The length of this triplet repeat may affect receptor expression. Recent publications focusing on length variations in both coding and non-coding region of genes showed biological importance and association to human diseases, such as in Huntington disease, myotonic dystrophy and Fragile X syndrome.2 Repeats in non-coding regions (i.e., promoter region) can have a significant impact on the gene including generation of chromosome fragility, silencing of the gene and modulation of transcription and translation of the protein.2

Aim of the PhD project:The aim of this project is to generate by molecular cloning several plasmid vectors which contain variable numbers of triplet repeats (VNTRs) within the H4 receptor promoter region in frame to a luciferase reporter gene which will the transfected into cells. The luciferase reporter gene will be activated by the H4 promoter which will create a luminescent read-out in transfected cells. Research will also encompass patient DNA samples, where polymorphism will be linked to conditions such as childhood atopic dermatitis through collaboration with Our Lady Childrens Hospital, Crumlin in Dublin.

1. Micallef S and Sasse A. Polymorphisms and genetic linkage of histamine receptors (2013). Life Sci. 93(15):487-94. 1. Usdin K The biological effects of simple tandem repeats: Lessons from the repeat expansion diseases (2008). Genome Res. 18:10111019.1.

This PhD project will bring research from the bench (molecular cloning) to the bedside (patient DNA). The student will be receiving training from postdoctoral researchers and the academic supervisor.

Trinity Biomedical Sciences Institute (TBSI) where the laboratories are located is an environment where innovative and interdisciplinary approaches are leading to scientific discoveries of biomedical importance, ultimately giving rise to better patient care.

The Trinity PhD is a structured PhD and students can access discipline-specific training, as well as generic and transferable skills. All PhD students are eligible to participate in the Innovation Academy which offers a Postgraduate Certificate in Innovation and Entrepreneurship to assist PhD students identify and exploit the value within their research.

Please indicate the graduates of which disciplines that should apply:

Pharmacy, Pharmaceutical Sciences, Biochemistry, Biological Chemistry, Molecular Biology.

Cincia sem Fronteiras / Science Without Borders Priority Area:Please indicate the specific programme priority area under which the proposed PhD project fits- choose only one (tick box):

Engineering and other technological areas

Pure and Natural Sciences (e.g. mathematics, physics, chemistry)

Health and Biomedical Sciencesx

Information and Communication Technologies (ICTs)

Aerospace

Pharmaceuticals

Oil, Gas and Coal

Renewable Energy

Minerals

Biotechnology

Nanotechnology and New Materials

Technology of prevention and remediation of natural disasters

Biodiversity and Bioprospection

Marine Sciences

Creative Industry

New technologies in constructive engineering