Dr Andreas Werner
Reader in Molecular Biology
- Email: firstname.lastname@example.org
- Telephone: +44 (0) 191 208 6990
- Fax: +44 (0) 191 208 7424
- Address: Institute for Cell and Molecular Biosciences
University of Newcastle upon Tyne
Catherine Cookson Building
Newcastle upon Tyne
I am a keen tango dancer. My partner, Angela, and I organise Argentinean Tango events and teach in Tynemouth (www.tango-on-tyne.co.uk). The picture shows us dancing in Switzerland in the cold....
My research focuses on two major areas:
• Gene regulation by natural antisense transcripts
• Epithelial Na/phosphate transport
Natural antisense transcripts (NATs) represent an enigmatic phenomenon seen in all organisms but are increasingly prevalent in mammals. This indicates that NATs are selected for during evolution and have therefore a distinct biological role. Very recent work from our lab provided key evidence for suggesting a comprehensive and generally applicable model of NATs action: Sense and antisense transcripts are co expressed only during a short time period, possibly observed during early (embryonic) stem- or germ cell development. The two transcripts are fully processed to guarantee stability and freedom to diffuse in the nucleus. Both sense and antisense transcripts may form RNA duplexes- or, alternatively, traffic to the cytoplasm. The nuclear RNA hybrids are processed into short RNAs. The short RNAs are transported into the cytoplasm where both the sense and the antisense oriented strands are included into an RNA induced silencing complex. A yet unknown biochemical process that may include RNAi components and the complementary full-length sense or antisense RNA leads the accumulation of either sense or antisense short RNA.
Our results indicate that under physiological conditions the short RNA complementary to the antisense transcripts eventually prevails. Feedback to the transcriptional level will target and silence the antisense promoter.
To understand the biological benefit of the hypothesized model we assume that a protein encoding gene developed a mutation. In the presence of a complementary antisense transcript the gene will be scrutinized via the short RNA pathway. If the mutation reverses the short RNA strand selection the mutated sense transcript becomes silenced and only the second, unmutated copy of the gene stays active. For obvious reasons the proposed mechanism only proves beneficial for an organism if the second allele is functional.
To summarise, we suggest that antisense transcripts help to reduce the impact of mutaions. (The manuscript containing all the relevant data is submitted, further details are also given on the narna webpage: www.narna.ncl.ac.uk)
Inorganic phosphate (Pi)
Inorganic phosphate (Pi) is an essential component in every cell, think of ATP or phosphorylation of proteins, and every organism controls the level of phosphate in its body fluid tightly. Pi is an important component of our diet, we take it up in the intestine and excrete the spare component via the kidney. Different isoforms of a membrane transport protein called NaPi-II are involved in both intestinal absorption and renal excretion. We are particularly interested in two aspects of these proteins. First, we investigate the impact of a protein motive, an extended stretch of cysteine residues in the C-terminus of the transporter, on intracellular protein trafficking. We found that lipid anchors (palmitic acid) are attached to the cysteine stretch. The lipid anchor is indeed crucial for the correct delivery of the transporter to the plasma membrane. Second, we plan to lock at the contribution of specific amino acids to substrate selection (how can the transporter distinguish between the similar ions phosphate and sulphate) and transport efficiency (how does phosphate translocate through the membrane protein). For this purpose we will mutate the phosphate transporter and express it in Xenopus oocytes. We will then measure the transport efficiency and compare the data to unmutated controls. These experiments are performed in collaboration with Dr. Ian Forster at the Institute of Physiology, Zurich, Switzerland.
Figure 1. The core and the C-terminus of the Na/Pi cotransporter are both important for intracellular trafficking in cultured cells (MDCK). Red stains the apical membrane of the cells, green represents the transporter. Yellow indicates and overlay of green and red, hence apical localisation of the transporter.
Qualifications: Teaching degree, Secondary School level (French German, History and PE, Journalism
Coordinator of the international antisense RNA interest group
Biomedical Sciences Course, first year: Respiratory Physiology, Integrative Physiology, Module Leader
Dental Medicine, first year: Respiratory Physiology, Integrative Physiology
Biomedical Sciences Course, third year: RNA biology and Project supervision
- Patti M, Fenollar-Ferrer C, Werner A, Forrest LR, Forster IC. Cation Interactions and Membrane Potential Induce Conformational Changes in NaPi-IIb. Biophysical Journal 2016, 111(5), 973-988.
- Piatek MJ, Henderson V, Zynad HS, Werner A. Natural antisense transcription from a comparative perspective. Genomics 2016, 108(2), 56-63.
- Patti M, Fenollar-Ferrer C, Werner A, Knopfel T, Forrest L, Forster I. Functional Identification of the Na1 Site of the Phosphate Cotransporter NaPi-IIa. In: 59th Annual Meeting of the Biophysical Society. 2015, Baltimore, Maryland: Cell Press.
- Fenollar-Ferrer C, Forster IC, Patti M, Knoepfel T, Werner A, Forrest LR. Identification of the First Sodium Binding Site of the Phosphate Cotransporter NaPi-IIa (SLC34A1). Biophysical Journal 2015, 108(10), 2465-2480.
- Werner A, Piatek MJ, Mattick JS. Transpositional shuffling and quality control in male germ cells to enhance evolution of complex organisms. Annals of the New York Academy of Sciences 2015, 1341, 156-163.
- Werner A, Cockell S, Falconer J, Carlile M, Alnumeir S, Robinson J. Contribution of natural antisense transcription to an endogenous siRNA signature in human cells. BMC Genomics 2014, 15, 19.
- Piatek MJ, Werner A. Endogenous siRNAs: regulators of internal affairs. Biochemical Society Transactions 2014, 42, 1174-1179.
- Fenollar-Ferrer C, Patti M, Knopfel T, Werner A, Forster IC, Forrest LR. Structural Fold and Binding Sites of the Human Na+-Phosphate Cotransporter NaPi-II. Biophysical Journal 2014, 106(6), 1268-1279.
- Fenollar-Ferrer MC, Patti M, Knoepfel T, Werner A, Forster IC, Forrest LR. Structural Model of the Human Sodium-Phosphate Cotransporter NaPi-II. In: 58th Annual Meeting of the Biophysical-Society. 2014, San Francisco, CA: Cell Press.
- FenollarFerrer C, Patti M, Forster I, Werner A, Forrest L. A structural model for the Na/phosphate transporter type II (SLC34A1). PNAS 2013. Submitted.
- Werner A. Biological functions of natural antisense transcripts. BMC Biology 2013, 11, 31.
- Werner Andreas, Cockell Simon, Falconer Jane, Alnumeir Sammer, Robinson John. Production of small genic RNAs and endogenous siRNAs from sense/antisense transcripts in human cells. Genome Biology 2013. Submitted.
- Werner A, Mattick JS. Strategies for enhanced evolvability of complex organisms: transpositional shuffling and screening in male germ cell development. Molecular Biology and Evolution 2013. Submitted.
- Wight M, Werner A. The functions of natural antisense transcripts. Essays in Biochemistry 2013, 54, 91-102.
- Werner Andreas. Processing and Regulatory Impact of Endogenous siRNAs in Animals. In: Morris, K.V, ed. Non-coding RNAs and Epigenetic Regulation of Gene Expression: Drivers of Natural Selection. Norfolk: Caister Academic Press, 2012, pp.31-46.
- Forster I, Hernando N, Sorribas V, Werner A. Phosphate Transporters in Renal, Gastrointestinal, and Other Tissues. Advances in Chronic Kidney Disease 2011, 18(2), 63-76.
- Bakrac B, Podlesek Z, Lakey JH, Werner A, Anderluh G. Equinatoxin, a eukaryotic pore-forming toxin used as a specific marker for cellular sphingomyelin. In: 34th FEBS Congress. 2009, Prague, Czech Republic: FEBS Journal: Wiley-Blackwell.
- Werner A, Sayer JA. Naturally occurring antisense RNA: function and mechanisms of action. Current Opinion in Nephrology & Hypertension 2009, 18(4), 343-349.
- Carlile M, Swan D, Jackson K, Preston-Fayers K, Ballester B, Flicek P, Werner A. Strand selective generation of endo-siRNAs from the Na/phosphate transporter gene Slc34a1 in murine tissues. Nucleic Acids Research 2009, 37(7), 2274-2282.
- Werner A, Carlile M, Swan D. What do natural antisense transcripts regulate?. RNA Biology 2009, 6(1), 43-48.
- Werner A. Gene Regulation by Natural Antisense Transcripts. In: Taylor JC; Williams AJ, ed. Research Progress in Antisense Elements (Genetics). New York: Nova Biomedical Books, 2008, pp.87-123.
- Werner A, Schmutzler G, Carlile M, Miles CG, Peters H. Expression profiling of antisense transcripts on DNA arrays. Physiological Genomics 2007, 28(3), 294-300.
- Mobjerg N, Werner A, Hansen SM, Novak I. Physiological and molecular mechanisms of inorganic phosphate handling in the toad Bufo bufo. Pflugers Archiv European Journal of Physiology 2007, 454(1), 101-113.
- McHaffie GS, Graham C, Kohl B, Strunck-Warnecke U, Werner A. The role of an intracellular cysteine stretch in the sorting of the type II Na/phosphate cotransporter. Biochimica et Biophysica Acta - Biomembranes 2007, 1768(9), 2099-2106.
- Werner A. Natural antisense transcripts. In: Gossen, M, ed. Encyclopedic Reference of Genomics and Proteomics in Molecular Medicine. Berlin, Germany: Springer, 2006.
- Werner A. Natural antisense transcripts. RNA Biology 2005, 2(2), 53-62.
- Werner A, Berdal A. Natural antisense transcripts: Sound or silence?. Physiological Genomics 2005, 23(2), 125-131.
- Graham C, Nalbant P, Scholermann B, Hentschel H, Kinne RKH, Werner A. Characterization of a type IIb sodium-phosphate cotransporter from zebrafish (Danio rerio) kidney. American Journal of Physiology - Renal Physiology 2003, 284(4), F727-F736.
- Coloso RM, King K, Fletcher JW, Weis P, Werner A, Ferraris RP. Dietary P regulates phosphate transporter expression, phosphatase activity, and effluent P partitioning in trout culture. Journal of Comparative Physiology B: Biochemical, Systemic, and Environmental Physiology 2003, 173(6), 519-530.
- Kirschner U, Van Driessche W, Werner A, Wehner F. Hypertonic activation of phospholemman in solitary rat hepatocytes in primary culture. FEBS Letters 2003, 537(1-3), 151-156.
- Dehmelt L, Schrage A, Hagnia M, Nalbant P, Musson J, Traebert M, Arpin-Bott M-P, Hinne RKH, Kaissling B, Robinson JH, Werner A. A novel isoform of the Shank adaptor protein family (Shank 3b) is expressed in immune cells and colocalizes with actin. Journal of Cell Science 2002. Submitted.
- Werner A, Preston-Fayers K, Dehmelt L, Nalbant P. Regulation of the NPT gene by a naturally occurring antisense transcript. Cell Biochemistry and Biophysics 2002, 36(2-3), 241-252.
- Werner AMC, Sharpe LT. Spatial features and chromatic adaptation. Perception 2002, 31(supplement), 16.
- Werner A, Kinne RKH. Evolution of the Na/Pi cotransport system type II (Napi-II). American Journal of Physiology 2001, 280(2), R301-312.
- Werner A, Kinne RKH. Evolution of the Na-P-i cotransport systems. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology 2001, 280(2), R301-R312.
- Bohmer C, Wagner CA, Beck S, Moschen I, Melzig J, Werner A, Lin J-T, Lang F, Wehner F. The shrinkage-activated Na+ conductance of rat hepatocytes and its possible correlation to rENaC. Cellular Physiology and Biochemistry 2000, 10(4), 187-194.
- B. Kohl, C. A. Wagner, B. Huelseweh, A. E. Busch and A. Werner. The Na+-phosphate cotransport system (NaPi-Pi) with a cleaved protein backbone: implications on function and membrane insertion. Journal of Physiology-London 1998, 508, 341-350.
- B. Huelseweh, B. Kohl, H. Hentschel, R. K. H. Kinne and A. Werner. Translated anti-sense product of the Na/phosphate co- transporter (NaPi-II). Biochemical Journal 1998, 332, 483-489.
- I. C. Forster, C. A. Wagner, A. E. Busch, F. Lang, J. Biber, N. Hernando, H. Murer and A. Werner. Electrophysiological characterization of the flounder type II Na+/P-i cotransporter (NaPi-5) expressed in Xenopus laevis oocytes. Journal of Membrane Biology 1997, 160, 9-25.