“Clever” DNA may help bacteria survive and How DNA is “edited” to correct genetic diseases

1. “Clever” DNA may help bacteria
survive and How DNA is “edited” to
correct genetic diseases.
Carolina Carvajal Miranda
Medicine Student
Universidad Pontificia Bolivariana
Medellín

2. FOLDING
Molecular biology
Medical student
3° Semester
Teacher
Lina Maria Martinez. S
July 28, 2014
Medellin, Colombia
Bibliography
Medical Utility
With the knolege and the
investigation studies of the
DNA structure, scientists can
now aproach certain
mecanisms in a large form.
The change in DNA structure
can now be the key
phenomenon that will allow us
to understand how certain
bacterias can become active
when transfered from a specific
enviroment to the human
body, and even, in some cases,
become more eficient in their
reproduction and survival
mecanisms.
Also, the discovery of specific
funtions of some enzyms that
can edit and restore genes can
take us closer to cure and treat
genetic diseases and gene
mutation alterations in order to
help patients with severe
medical conditions.
Carolina Carvajal Miranda
DNA Estructure
•Mark D. Szczelkuna, Maria S.
Tikhomirovab, Tomas Sinkunasd, Giedrius
Gasiunasd, Tautvydas Karvelisd, Patrizia
Pscherac, Virginijus Siksnysd and Ralf
Seidel. Direct observation of R-loop
formation by single RNA-guided Cas9
and Cascade effector complexes. PNAS,
May 2014
•Monash University. "'Clever' DNA may help
bacteria survive." ScienceDaily.
ScienceDaily, 4 June 2014.
<www.sciencedaily.com/releases/2014/06/1
40604105536.htm>.

3. FOLDING
How DNA is 'edited' to
correct genetic diseases
An international team of scientists at the
Universities of Bristol, Münster and the
Lithuanian Institute of Biotechnology
observed the mecanisms by which a type
of enzymes called CRISPR bind and alter
the structure of DNA. This discovery can
now help to identify how this genome
editing tools work and how they can be
used to correct genetic diseases in
humans. These enzymes are believed to
target a single combination of letters within
the three billion base pairs of the DNA
molecule. The targeting process requires
the CRISPR enzyme to pull apart the DNA
strands and insert in them a similar RNA
to form a sequence-specific structure
called an 'R-loop'.
This single molecule assays can helped
understand the influence of DNA
sequences on R-loop formation. “In the
future this may help in the rational re-
engineering of CRISPR enzymes to
increase their accuracy and minimise off-
target effects. This will be vital if we are to
ultimately apply these tools to correct
genetic diseases in patients."
'Clever' DNA may help
bacteria survive
A recent research study, published in the
journal Proceedings of the Royal Society
Interface, has shown that bacterial DNA
can change from the regular double helix
B form , to the more compact A-DNA
form, using a specialized process called
the B-A-B transition. This process takes
pleace when bacteria is faced with
adverse conditions, and doesn’t affect its
capacity to function normally and
reproduce.
Even though there is no biological reason
why this mecnism also happends in the
human body cells, its recurrence in
bacteria results very interesting.The
interdisciplinary team at Monash
investigated four species of bacteria.
They used a carefull process of hydrating
and then, dehydrating the cells and
studied the results with a infrared based
tecnique that detects DNA vibrations. It
was found that all species studied
underwent the BAB transition.
With the first phase complete, now
investigations teams can center their
attention on working with other
conditions such as temperature, pH
levels, oxygen, nutrients and
antimicrobials and discover if DNA
structur changes occur as well.
Introduction
The DNA has the vital job in
carrying the genetic code
which defines all living
organisms. The complex role of
the DNA gives us a crucial
target
point that
can be mo-
dified and
edited to
obtain cer-
tain caracte-
ristics. The discovery of
bacteria that can reshape their
DNA to survive dehydration
and other extreme conditions,
or the capacity of certain
enzymes to edit specific
secuences of DNA, gives us a
solid base to secure the fact
that variability in DNA can
complitly change the course of
the human body responce
mecanisms.
I think this discovery brings us a step
foward in the understanding of how
enzymes can edit and modify specific
secuences of DNA, bringing us closer in
treating genetic deseases.
In my opinion, this research can now explain how
certain microorganisms can develop extreme
resistance to adverce conditions, and later on, help
us develop a more specialized form of treatment to
attack infectant bacteria that survive using this type
mecanisms.
OBSERVATION
OBSERVATION

4. INTRODUCTION
• Bacteria can reshape
their DNA to survive
dehydration.
•Understanding how enzymes “edit”
genes, paving the way for correcting
genetic diseases in patients.

5. “Clever” DNA may help
bacteria survive(ScienceDaily, 4 June 2014 )
 Bacterial DNA can change from B-DNA (double helix) , to the more
compact A-DNA form, when exposed to adverse conditions such as
dehydration.

6. “Clever” DNA may help bacteria
survive(ScienceDaily, 4 June 2014 )
 B-A-B transition allows
structure change in response to
environmental variation.
 No impact on the ability to
function and reproduce.
 Unique structural alteration that
generates the B-DNA change to
A-DNA, and then revert back to
its original B-DNA form.

7. "Our findings may be important in understanding
how dormant bacteria that are transferred from dry
surfaces may become active and reproduce in the
human body,” Associate Professor Wood said.
“Clever” DNA may help bacteria
survive(ScienceDaily, 4 June 2014 )

8. “Clever” DNA may help bacteria
survive(ScienceDaily, 4 June 2014 )
B FORM
Bacteria can survive by adopting the A-DNA form after
the majority of water is removed.
A FORM
Dyhadration

9. “Clever” DNA may help bacteria
survive(ScienceDaily, 4 June 2014 )
 Infrared based tecnique detects DNA vibrations.

10. OBSERVATION
In my opinion, this research can now explain how
certain microorganisms can develop extreme
resistance to adverse conditions, and later on,
help us develop a more specialized form of
treatment to attack infectant bacteria that survive
using this type of mecanisms.

11. How DNA is “edited” to
correct genetic diseases
 Enzymes “edit” genes
paving the way for
correcting genetic
diseases in patients.
 CRISPR enzymes
(Cas9) can be used to
edit the human
genome.
(ScienceDaily, 26 May 2014)

13.  The targeting
process requires the
CRISPR enzymes
to pull apart the
DNA strands and
then insert the RNA
to produce a specific
sequence structure
called an 'R-loop'.
How DNA is 'edited' to correct
genetic diseasesScienceDaily, 26 May 2014)

14. How DNA is 'edited' to correct
genetic diseases
 DNA sequence influences
R-loop formation.
 Re-engineering of CRISPR
enzymes to increase
accuracy and minimize off-
target effects.
ScienceDaily, 26 May 2014)
Correct genetic diseases in
patients.

15. OBSERVATION
I think this discovery brings us a step foward in
the understanding of how enzymes can edit and
modify specific secuences of DNA, bringing us
closer in treating genetic diseases .

16. MEDICAL UTILITY

17. MEDICAL UTILITY
“Clever” DNA may help bacteria survive
•The discovery of the changes in DNA
structure under extreme circumstances is
a key point in the future development of
specific treatments for bacterial infections
that are dificult to deal with.
•It may also help us understand specific
mecanisms that microorganisms use and
identify key factors in their survival.

18. • Lastly, if biological proof of this mecanisms can be found in the human
body cells it may be a whole new starting point for scientists in the
treatment of diseases that put cells under temperature, pH levels,
oxygen, nutrients and antimicrobial stress.
MEDICAL UTILITY
“Clever” DNA may help bacteria survive

19. MEDICAL UTILITY
How DNA is “edited” to correct genetic diseases
•In the future, these studies can be used to
engineer enzymes alterating their target
points in the human DNA. This will be a
vital step in correcting genetic diseases in
patients.

20. BIBLIOGRAPHY
 MARTINEZ S., Lina Maria. Biologia molecular. 5. ed. Medellin: UPB.
Fac. de Medicina,
2009.265 p.
 Monash University. "'Clever' DNA may help bacteria survive."
ScienceDaily. ScienceDaily, 4 June 2014.
<www.sciencedaily.com/releases/2014/06/140604105536.htm>.
 Mark D. Szczelkuna, Maria S. Tikhomirovab, Tomas Sinkunasd,
Giedrius Gasiunasd, Tautvydas Karvelisd, Patrizia Pscherac,
Virginijus Siksnysd and Ralf Seidel. Direct observation of R-loop
formation by single RNA-guided Cas9 and Cascade effector
complexes. PNAS, May 2014