Androglobin is a novel hemoglobin, discovered in 20121. The hemoglobin of the erythrocyte is one the most studied proteins in science, however androglobin is paradoxically one of the least studied and understood proteins of the hemoglobin superfamily.
Androglobin is expressed in low levels in the lungs and high levels in the testes and may be involved in male fertility and lung disease (motile cilia being a common theme). Androglobin has a highly unusual arrangement with a circularly-permuted globin domain at its center (i.e. the second half of the protein is expressed before the first half), split by a calmodulin-binding domain. This is preceded by calpain domains, however, much of the protein has no known correlation with protein sequences.
The structure of this complex multi-domain protein of 1667 residues (cf ~140 residues for canonical hemoglobins) is completely unknown outside of Essex: the lack of recombinant protein studies is reportedly due to the instability of the heme domain when expressed2. However, we have overcome the stability issue and characterized much of its heme function, including interaction with calmodulin. (For the molecular dynamics of a model heme domain structure see https://youtu.be/UAT7OtHvzSI
). Thus, we are in a unique position to discover the fundamental properties of this protein. Through our initial research we believe that the protein has multiple functions related to calcium cell-signalling and nitric oxide regulation and is potentially important in the development of germ cells.
The project aim is to investigate the structural and functional aspects of the heme domain of androglobin and its interaction with other androglobin domains or external proteins such as calmodulin through various biochemical experiments designed through the molecular modelling. Conditions to generate crystal structures of the globin domain have so far eluded us, but the significant increase in spectra quality of the heme domain in the presence of calmodulin suggests that crystallizing the heme in the presence of other domains is likely to be successful. Additionally, the protein will be expressed in human cancer cell lines, either transiently or through stably transfected protein, for cell stress studies. The unusual structural arrangement of this novel androglobin protein and the presence of calpain, known to control key physiological processes, make this a stimulating project with implications in male fertility issue and potentially cancer research3.
Entry requirements and application procedures
Highly motivated applicants with, or expecting, a good degree in the broad area of Life Sciences are encouraged to apply.
Applications should be submitted electronically by 24th April 2019 see here for details https://www.essex.ac.uk/pgapply/enter.aspx
You are encouraged to contact the supervisor before application: [email protected]
and [email protected]
you have any queries with the online application process, please contact [email protected]
For general information about the School of Biological Sciences at the University please visit our webpages http://www.essex.ac.uk/bs/
The University of Essex
The University of Essex is University of the Year - Times Higher Education (THE) Awards 2018. In the recent Research Excellence Framework 77% of research at the University of Essex research is ’world leading’ or ’internationally excellent’ (REF 2014).We offer world-class supervision and training opportunities and our research students work at the heart of an internationally-acknowledged and well-connected research community. In the 2013 Postgraduate Research Experience Survey, 84% of respondents said that they were satisfied with the quality of their research degree. At Essex we win awards for our pioneering student support schemes. We are the most recent winners of the prestigious Times Higher Education award for Outstanding Support for Students. Essex is a genuine global community. With more than 130 countries represented within our student body, and 40% of our students from overseas, we are one of the most internationally-diverse universities in the UK.