Staff serving as external examiners

University of Chester,
Biomedical sciences programme 2005-2009

External examiner for PhDs, Universities of Aberdeen, Chester, Strathclyde, Warwick, UWE, Bristol and Portsmouth.

Research interests

Avent lab current Research activity

 

1.     Free fetal DNA (ffDNA) in maternal plasma (Dr Tracey Madgett, Kelly Sillence, Hannah Thompson)

ffDNA represents the greatest potential for delivering routine non-invasive prenatal diagnosis, and especially coupled with next-generation sequencing (NGS) technologies could easily become the norm for the diagnosis of aneuploidy. Unfortunately  NGS technology presently is prohibitively expensive, and we have developed methods for the enrichment of fetal DNA and depletion of maternal DNA in maternal plasma samples. The study is set to exploit the digital PCR platform we have just acquired within the Plymouth post-genomics Centre, which is due to open in November 2011. The methods involve relatively straightforward manipulations of the PCR procedure to inhibit the amplification of maternal DNA, and in one assay to actively destroy it. The work is currently funded by the NIHR, and is in collaboration with Prof Lyn Chitty (ICH/UCL/GOSH).

2.     Analysis of fetal cells in maternal blood (Dr Michele Kiernan)

Despite the huge advances in the study of ffDNA (described above) there are distinct advantages in being able to work with single purified fetal cells. Based  on our previous work, we are isolating fetal erythroblasts using our FACSAria 2 flow cytometer, and investigation the transcriptome using next-generation sequencing. With this we hope to identify fetal erythroblast specific biomarkers to enable their more efficient isolation from maternal blood samples. We consider the lack of suitable biomarkers of erythroid cells to be a key factor in the ineffectiveness of fetal cell isolation methodologies in the past.

3.     Molecular Investigation of Mechanisms of red cell turnover (Dr Kris Jeremy)

Continuing a project started in the 2000s, we are studying the role of the red cell form of CD47 and how huge numbers of effete red cells are removed from the circulation on a daily basis. We are using proteomics techniques to achieve this and are using normal red cells and CD47 deficient cells. Post-translational modification (PTM), involving PKA and PKC phosphorylation of red cell membrane components are critical in this process, and we are studying the precise molecular pathway involved. We have recently obtained a Thermo orbitrap Velos elite mass spectrometer (the first such instrument in the UK) to investigate the nature of the PTMs involved. The study is in collaboration with Prof Rob Barker (University of Aberdeen) as is funded by the Wellcome trust.

4.     New Serum Screening biomarkers for aneuploidy (Kelly Sillence)

We have identified a significant number of biomarkers using CVS samples from Down and non-Down mothers by transcriptomics, and by previous proteomics studies (see Heywood et al., (2011) in publications list). We are validating these markers after raising monoclonal antibodies to them. Many Down-specific changes involve PTMs and we will use our new Orbitrap velos mass spectrometer to identify their molecular nature- knowing precisely which protein species is involved. Study funded by the Fetal medicine Foundation in collaboration with Prof Kypros Nicolaides and Dr Ranjit Akolekar

 

5.     New roles for the CD47 glycoprotein (Dr Kris Jeremy)

       A study in collaboration with Prof Oliver Hanemann (PCMD), we are investigating the binding partners of CD47 in neural tissue, and then using CD47 ligands as potential new therapeutic agents against brain tumours, especially Schannoma.

4.     Next generation sequencing for blood groups (Amr Halawani, Malik Altayar, Tracey Madgett, Michele Kiernan, Tony Reynolds)

We have developed methodology to sequence the entire genomic segments of all clinically significant blood groups. This work has been performed on an Ion-Torrent PGM sequencer. Preliminary analysis of the KEL, FY, RHCE and RHD genes has revealed a hitherto unrealised level of variation within both coding and non-coding sequences. We will develop this technology to be sufficiently robust for diagnostic use, and will use new NGS technologies as soon as they are available.

Research degrees awarded to supervised students

PhD completions

Jill Storry (2000) UWE, Bristol (Second Supervisor)

Wendy Liu (2001) University of Bristol (Director of Studies)

Kirstin Finning (2003) UWE, Bristol (Director of Studies)

Emma Court (2003) UWE, Bristol (Second supervisor)

Lucy Skinner (2004) UWE, Bristol (Director of Studies)

Charlotte Spink (2004) UWE, Bristol (Second supervisor)

Zoe Plummer (2006) UWE, Bristol (Director of Studies)

Lisa Spary (2007) UWE, Bristol (Second supervisor)

Amanda Wallington (2007) UWE, Bristol (Director of Studies)

Kevin Kemp (2007) UWE, Bristol (Second supervisor)

Kelly Sanders (2008) UWE, Bristol (Second supervisor)

Sina Mueller (2009) University of Goettingen (Second supervisor) MD

Alistair Kemp (2009) UWE, Bristol (Second supervisor)

Wei Yuan (2011) University of Bristol (Second Supervisor)

Charlene Porter (2011) University of Aberdeen (Second supervisor)

Kin Choi (2011) University of Bristol (Second Supervisor)

Kris Jeremy (2012) UWE, Bristol (Director of Studies)

Amr Halawani (2016) PUPSMD (Director of Studies)

Kelly Silence (2016) PUPSMD (Director of Studies)

Grants & contracts

Grants since 2003
(1)    EU Framework V quality of Life programme “Cell factory” 2003-2006. Blood Grouping and Genotyping: Improving patient safety and Blood Transfusion compatibility. UWE, Bristol lead partner (N.D. Avent consortium co-ordinator, partners in Germany, Netherlands, Sweden, Czech Republic and Spain) (BloodGen consortium) €2,350,000 (http://www.bloodgen.co.uk). (2)    National Blood Service 2003-2008 Establishment of the Erythrocyte Proteome and Blood Grouping using Molecular Phenotyping  £345,494 (with Prof Marion Scott, Bristol Institute for Transfusion Science) (3)        EU Framework VI Special Advances in Fetal Evaluation (SAFE) network of excellence 12 million €. European Union framework VI - call genomics in health.  2004-2009 In collaboration with 52 EU partners (Dr Sinuhe Hahn co-ordinator). NDA Workpackage 3 leader, and chair of the network steering committee . UWE allocation - first 18 months €159,600, 2nd 18 months €376,800 (60 month project total) 3rd 18 months . (http://www.safenoe.org/) (4)        Mother and Baby trust, UK High Throughput non-invasive Genotyping £3,059 (With Dr Debbie Maddocks and Prof Peter Soothill) March 2004 (5)        EU Framework VI STREP – NEST Adventure 2005-2008 Isolation of fetal cells from maternal blood a nanomolecular approach (SAFER)" UWE allocation  €320,000 (http://www.etseq.urv.es/dinamic/SAFER/ ) Project co-ordinator Dr Ciara O’Sullivan  

(6)  “Transcriptomics of Down syndrome placental samples” 2008-2009 N.D. Avent and D.G. Maddocks, Fetal Medicine foundation £45,000

(7) “RAPID” Start date 01 January 2009-2014 National Institute of Health Research programme grant (Prof Lyn Chitty co-ordinator) £2 million total funding, University of Plymouth allocation  £50,000

(8) EUROGENTEST 2 Jan-2011-Jan 2014, EC-FP7 Standardisation of genetic testing in Europe, Workpackage leader, Non-Invasive Prenatal Diagnosis, University of Plymouth funding  €145,000

Conferences organised

Scientific organising committees

European Hematology Association
13th meeting, Copenhagen Denmark, June 2008
14th meeting, Berlin, Germany. June 2009
15th meeting, Barcelona, Spain, June 2010

Blood group Serology Reading (BGS)
2007 Meeting

Other academic activities

Consultancy

2006-2009 Consultant for Progenika Biopharma (Blood group genotyping)
2011-2015 Consultant for Grifols SA (Transfusion Medicine Advisory board)