Doctoral Student Positions Available
The Department of Biological and Environmental Science at the University
of Jyvaskyla, Finland, currently seeks to recruit doctoral students into
its doctoral programme, starting earliest 1 January 2015. The goal of
the Department is that the student completes the degree in four years.
Applications are invited to one of the research projects
Revealing chemical and structural dynamics of photoactivated
bacteriophytochromes by means of infra-red spectroscopy
Phytochromes are photosignaling proteins, which report the presence of
red light in the environment of the cell. In order to accomplish this
function they undergo rather large structural changes between resting
state and active state, which we have recently been able to track out.
In short, by measuring solution X-ray scattering and crystallography
of the photosensory unit of the bacteriophytochrome, a large opening
of the long scaffolding helices in the dimeric interface of the protein.
The bacteriophytochromes function as two-component systems (homo-dimers)
and thus the opening must be crucial for its function. Along the lines
of large quaternary changes, secondary structural changes, which must
be very important for opening and closing of the dimeric interface
(i.e. activating the protein), are detected.
In order to trace more detailed structural and chemical changes of the
phytochrome during the light activated reaction, we will utilize
vibrational spectroscopy on the bacteriophytochrome systems in time-
resolved manner. For this, we will use techniques, like FTIR, transient
IR-spectroscopy, and 2D-IR spectroscopy, which will report details of
the functional mechanism of the bacteriophytochromes.
The successful applicant should have a Masters degree either in
Biophysics, Cell and Molecular Biology, Chemistry or related areas.
Prior expertise on spectroscopy and/or protein biochemistry is
acknowledged.
Takala, Björling, Berntsson, Lehtivuori, Niebling, Hoernke, Kosheleva,
Henning, Menzel, Ihalainen, and Westenhoff: Signal amplification and
transduction in phytochrome photosensors. Nature 2014, 509, 245-249.
Lehtivuori, Rissanen, Takala, Bamford, Tkachenko, and Ihalainen:
Excited state properties of chromophore-binding domain of
bacteriophytochrome from Deinococcus radiodurans, J. Phys. Chem. B
2013, 117, 11049-11057.
Contact person: Professor Janne Ihalainen
(janne.ihalainen@jyu.fi), Division of Cell and Molecular Biology
Following the uncoating of Echovirus 1 by means of vibrational labels,
fluorescence and Raman spectroscopy
In our group we have recently elucidated several details of the
infectious entry of the human pathogens, enteroviruses. Our present
focus is to study the mechanisms of virus uncoating inside cytoplasmic
endosomes, as well as the release of the viral genome from the endosomes
to the cytoplasm to start efficient replication. These studies are
important to gain fundamental understanding of virus cell biology, but
also to develop antiviral strategies against acute and chronic viral
infections. In order to do that, we have developed both rigorous
purification and novel labeling methods for enteroviruses as well as
quantitative algorithms for imaging (www.bioimagexd.net). Together with
the group of Janne Ihalainen, we have recently used Raman spectroscopy
to selectively gain signatures for uncoating intermediates of Echovirus 1.
In traditional live cell fluorescence microscopy proteins under study are
fused with fluorescent protein markers and the DNA and the RNA are
labeled non-specifically with DNA and RNA attaching dyes. However, it is
known that the fluorescent fusion proteins are dysfunctional or have
improper intracellular location, because the bulky fluorescent protein
can disturb the diffusion and binding dynamics of the protein. We are
presently synthesizing new molecules that may be used for both
fluorescent in vivo labeling of the virus (genome and capsid) for
confocal imaging and as vibrational labels for Raman microspectroscopy.
In this PhD project, the succesfull candidate will incorporate Raman
vibrational groups or unnatural nucleotides to the virus and study
the Raman spectroscopic signatures in their native, uncoating
intermediate, and disrupted particles in vitro in a similar manner
as in our previous study (Ruokola et al. 2014). The IR-labeled samples
are also studied in cells by utilizing Raman microspectroscopy and in
parallel, fluorescently labeled viruses are studied live by confocal
microscopy. These studies will eventually provide novel information
of the ambient conditions that lead to succesfull virus uncoating in
live cells in endosomes.
The successful applicant should have Masters degree either in Cell and
Molecular biology, Chemistry or related areas. Prior expertise on
spectroscopy, fluorescence labeling or biological imaging is
acknowledged.
Pasi Kankaanpää, Lassi Paavolainen, Silja Tiitta, Mikko Karjalainen,
Joacim Päivärinne, Jonna Nieminen, Kalle Pahajoki, Heikki Uuksulainen,
Varpu Marjomäki, Jyrki Heino, Daniel White: BioImageXD - an open
general purpose and high throughput image processing and analysis
platform for biomedical images, Nat Methods. 2012 Jun 28;9(7):683-9
Varpu Marjomäki, Tanja Lahtinen, Mari Martikainen, Jaakko Koivisto,
Sami Malola, Kirsi Salorinne, Mika Pettersson, and Hannu Häkkinen:
Site-specific targeting of enterovirus capsid by functionalized gold
nanoclusters, PNAS 2014 Jan 28;111(4):1277-81.
Huttunen M, Waris M, Kajander R, Hyypiä T, Marjomäki V.Coxsackievirus
A9 Infects Cells via Non-acidic Multivesicular Bodies. J Virol. 2014
May;88(9):5138-51PMID: 24574401
Ruokola P, Dadu E, Kazmertsuk A, Häkkänen H, Marjomäki V, Ihalainen
JA Raman spectroscopic signatures of echovirus 1 uncoating. J Virol.
2014 Aug;88(15):8504-13. doi: 10.1128/JVI.03398-13.
Contact person: Senior Lecturer Varpu Marjomäki
(varpu.s.marjomaki@jyu.fi), Division of Cell and Molecular Biology
The deadline for applications is on 7 November 2014. Application is
exclusively through the online procedure available at:
https://www.jyu.fi/science/en/application-form-doctoral-students.
Application should be accompanied with updated CV and a 1-page cover
letter, outlining the motivation for applying for the doctoral student
position and includes a list of 1-2 references and their contact
information. Each supervisor will select one best candidate for their
own project based on the applications. These top candidates are asked
to write a 2-page long research plan on the thesis topic and invited
to an interview. Only one application per candidate is accepted.