SBL100-­‐Theory-­‐Class-­‐Lecture

 
 SBL100-­‐July-­‐2019-­‐Semester-­‐I  
Slot  C-­‐Tuesday/Wednesday/Friday-­‐8am  to  9.00am  
Course  contents:  
Dr.  Amitabh  Mukhopadhyay  
Evolu'on  and  Molecular  perspec'ves,  Classifica'on  of  systems  in  biology,  
Cellular  assemblies,  Geometry,  structures  and  energe'cs  
Fundamental  units  of  life,  From  prokaryotes  to  eukaryotes  
Single  to  mul'cellular  organisms  
Dr.  Vivekanandan  Perumal  
Infec'on  and  disease,  Evolu'on  in  disease-­‐synergy  and  antagonism  
Immunology,  Apoptosis,  Epigene'cs  
Dr.  Ashok  Patel  
Biological  machines,  Gene'c  engineering,  gene  regula'on,  Stem  cells  ,  Cancer  
biology,  drug  design,  Techniques  in  biophysics  and  biochemistry,  Aging  
Why  you  wish  to  study  Biology?  
 
Biology  is  very  ………………………………..subject.  
 
• Our  goal  is  to  make  you  (Engineering  students)  learn  and  
understand  HOW  BIOLOGY  WORKS  
• In  contrary  Biology  students  wish  to  understand  WHAT  
BIOLOGY  IS.  
• Goal  is  to  make  aware  about  basic  biology  concepts.  
• You  can  apply  your  knowledge  to  novel  situa'ons.  
• You  can  find  mo'va'on  to  contribute  in  various  
researches  in  biology.  
• e.g.    gene'c  engineering,  biomedical  devices,    biological  
machines  
•  Bio  =  life  
•  ...ology  =  the  study  of  
•  Biology  is  the  science  that  studies  life  or  
living  organism.  
•  How  they  interact  with  one  another  and  their  
environment.  
•  Biology  is  an  fascina'ng  and  important  
subject  because  it  drama'cally  affects  our  
daily  lives  and  our  futures.  
Let us ask a fundamental question
What makes something alive?
What characteristics do define life?

All living things share certain key characteristics,

ü order,
ü sensitivity,
ü growth,
ü development,
ü reproduction and
ü homeostatsis

The knowledge from biology will be a fundamental gain how

to manage world’s resources in wise manner, to prevent or
cure diseases, to improve quality of lives.
  The  Science  of  Life  
•  Biology  unifies  much  of  natural  life  

•  Biology  aOempts  to  define  life  

•  Biology  Living  reveals  a  hierarchical  

organiza'on  of  living  systems  
 Proper'es  of  Life  
•   Living  organisms:  
– are  composed  of  cells  (Cellular  Organiza'on)  
– are  complex  and  ordered  (Ordered  Complexity)  
– respond  to  their  environment  (Sensi'vity)  
– can  Grow,  Develop  and  Reproduce  
– obtain  and  use  energy  (Energy  U'liza'on)  
– maintain  internal  balance  (Homeostasis)    
– allow  for  Evolu'onary  Adapta'on    
 
BeauXful  Nature  
Biological  moXvaXon  has  led  to  discover  
 
1.  lubricin  found  in  synovial  fluids  of  joints  super-­‐
low  fricXon  uXlized  in  IC  engines    

2.  superhydrophobic  properXes  of  gecko  skin  anX-­‐

we^ng  and  self-­‐cleaning  properXes  

3.  fricXon-­‐reducing  shark  skin  nanoparXcle  coaXngs  

surface  texturing,  hygienic  floor-­‐wall  material    

4.   soc  lithography  lotus  leaf  and  air  lubricaXon  

phenomenon  applied  to  propel  boats,  ships,  and  
torpedoes  faster  by  reducing  skin  fricXon  
underwater  

5.  pitcher  plant  led  to  the  innovaXon  of  self-­‐healing  

and  slippery  liquid-­‐infused  porous  surfaces.  
• Recent  advancement  at  IIT  Delhi  
• A  DiagnosXc  tool  for  detecXng  cancer  Xssues  
• Flexmo  crutch  to  assist  the  specially-­‐abled.  

• Rice  straw  into  cellulosic  pulp  for  cups  and  plates  

• Water  acXvated  powerless  heaXng  system.  

• UAV  (Aerial  Vehicle)  and  RoV  (Underwater  Vehicle)  by  FITT  Incubated  
BotLabs  Dynamics.  

• Bioresorbable  Cardiac  Stent    

• Scrambled  egg  based  on  plant  protein  

• Personal  Body  Armour  by  Joint  Advanced  Technology  Centre    

• Waterless  shampoo,  waterless  body  bath  by  Clensta  InternaXonal  (a  FITT  
incubated  startup)    
Researchers  at  IIIT  Hyderabad  are  using  machine  learning  for  diagnosis  and  prognosis  of  
cancer  by  analysing  microscopic  examinaXon  of  Xssue  by  computaXonal  models  

The  IIITH  research  team  has  been  able  to  classify  33  different  types  of  cancers  Xll  now  using  
histopathological  images  from  the  US  government-­‐funded,  Cancer  Genome  Atlas  Project  
 
MIT  “Russian  Doll”  teams  were  awarded  a  total    of  $23  Million  to  fight  brain  tumors  
 
use  nanoparXcles  to  carry  mulXple  drug  therapies  to  treat  brain  tumor.    
 
“Russian  doll-­‐like”  parXcles  —  to  deliver  drug  combinaXons  to  brain  tumors  
 
Temozolomide,  which  is  usually  the  first  chemotherapy  drug  
given  to  glioblastoma  paXents.  
 
Bromodomain  inhibitors  JQ-­‐1  are  believed  to  interfere  with  
cells’  ability  to  repair  DNA  damage  
 
Coated  liposomes  with  transferrin.  
 
Transferrin  binds  to  proteins  of  tumor  cells  killing  at  the  tumor  
site  while  avoiding  healthy  brain  cells  
 
researchers  from  IIT  GuwahaX,  engineered  meat  in  their  
laboratory,  which  is  equally  nutriXous  and  tasty  
examples  of  what  can  result  when  engineering  knowledge  is  applied  
to  solving  problems  in  medicine  and  biology:  
• Cardiac  stents  
• Defibrillators  
• EKGs  
• Holter  monitors  
• Mobile  Cardiac  OutpaXent  Telemetry  (MCOT)  
• EEGs  
• Medical  imaging  (x-­‐ray,  CT,  MRI,  fMRI,  PET)  
• The  cochlear  implant  
• Anesthesia  monitoring  equipment  
• PrescripXon  monitoring  for  pharmacies  
• ArXficial  hearts  and  valves  
• Pacemakers  
• Medical  venXlator  systems  
• RehabilitaXon  systems  
• ProstheXcs  
• LASIK  surgery  
• daVinci  surgical  robots  
• Transcatheter  valve  replacement  and  repair  devices  
• And  many  more………….  
RelaXon  between  Biology  and  technology  
Enabling  

Biological  
understanding,  
Engineering  and   Improved  
Technology   lifestyle,  
Human  healths  

New  engineering  principles  and  designs  

Need  Bright  Engineers  with  great  ideas,  excitement,    and  mo'va'on  
students  from  chemistry,  computer  science,  math,  physics  
and  engineering  have  equal  chance  to  contribute  in  biology  
Implica'ons  
of  
technology  
in  societal  
applica'ons  
Understanding  funcXons  of  Biological  systems  are  
very  very  complex  
Biological  machines  convert  chemical  (free)  energy  to  
mechanical  work,  informaXon.  
 
How  do  they  work?  
•What  structural  and  chemical  features  are  important?  
 
•How  is  chemical  energy  uXlized,  converted  into  force,  
moXon?  
•What  role  is  played  by  thermal  energy  and  fluctuaXons?  
 
•What  is  unique  about  the  nano-­‐scale:  what  difference  
does  small  size  make?  
 Biological  systems  are  very  very  complex,  the  misbalance  at  any  
level,  gene  or  cells  or  Xssues  leads  to  various  diseases.  
Disease  is  a  disorder  or  malfuncXon  of  the  mind  
                     or  body,  which  leads  to  a  departure  from  good  health.    
Can  be  a  disorder  of  a  specific  Xssue  or  organ  due  to  a  
single  cause.    E.g.  malaria.    
May  have  many  causes.  
O[en  referred  to  as  mul'factorial.  E.g.  heart  disease.    
Disease  are  diagnosed  by  a  doctor  analysing  the  symptoms  (physical  
and  mental  signs).  
Some  common  diseases  are  cancer,  malaria,  dengue,  HepataXs,  AIDS,  
Influenza,  HepaXXs  A,B,C,  Jaundice,  Tuberculosis,  schizophrenia,  
Alzheimer,  Parkinson,  cholera,  Typhoid  etc.  
There  are  sXll  very  very  severe  diseases  which  cannot  be  treated  so  
far  due  to  lack  of  proper  understanding  which  results  lack  of  proper  
medicines.  
We  will  study  various  aspects  of  biology  in  our  class  
 
What  are  biological  machines?    
 
How  can  we  study  them?  
 
What    is  geneXc  engineering?  
 
What  is  cancer?  
 
What  are  stem  cells?    
 
Why  do  we  age?  
Nature    is  the  best  engineer  and  evoluXon  is  the  best  design  

Think  yourself  and  compare  some  examples  

 
 
Common  examples  of  Biological  machines/  motors  are    
 

Video-­‐I-­‐Biomolecules  
Brain  funcXon   Video-­‐2-­‐brain-­‐funcXon  
The  brain's  func'on  as  part  of  the  Central  Nervous  System  (CNS)  is  to  
regulate  the  majority  of  our  body  and  mind's  func'ons.    
 
This  includes  vital  func'ons  like  breathing  or  heart  rate,  going  from  
basic  func'ons  like  sleeping,  ea'ng,  to  superior  func'ons  like  thinking,  
remembering,  reasoning,  or  talking.    
 
In  order  to  carry-­‐out  any  seemingly  simple  task,  our  brain  has  to  
perform  thousands  of  processes  to  ensure  that  we  properly  complete  
task.  Proper  brain  func'on  is  the  key  to  a  healthy  life.  
 
basic  vital  brain  func'ons  are  measured  by  the  structures  located  in  
the  hindbrain  (medulla,  pons,  cerebellum),  and  in  the  midbrain.    
 
However,  superior  brain  funcXons,  like  reasoning,  memory,  and  
aqenXon,  are  controlled  by  the  hemispheres  and  lobes  that  form  
part  of  the  cortex.    
 Anatomy  of  Brain  

male  and  female  brains  have  no  difference,  they  carry  out  the  same  funcXons  and  are  
virtually  indisXnguishable.    
The  only  thing  that  may  make  men  and  women  think  and  act  differently  are  hormones  
that  affect  how  the  brain  reacts.  
 ScienXst  decode  brain  funcXon  
with  neuromorphic  compuXng  
and  algorithms  how  the  
human  brain  works.  
how  it  idenXfies  and  avoids  
obstacles    
FoxP  determines  how  decisions  

•  The  brain  makes  up  2%  of  a  person's  weight.    

•  even  at  rest,  the  brain  consumes  20%  of  the  body's  energy.    
•  Average  power  consumpXon  of  a  typical  adult  is  100  Waqs  and  the  
brain  consumes  20%  of  this  making  the  power  of  the  brain  20  W.  
•  brain  is  capable  of  performing  10  quadrillion  (1016)  “calculaXons,”  
or  synapXc  events,  per  second  using  only  10  waqs  of  power.    
•  At  this  rate,  a  computer  as  powerful  as  the  human  brain  would  
require  1  gigawaq  of  power.  
•  100  billion  microscopic  brain  cells,  called  neurons,  produce  enough  
electrical  signals  to  power  a  small  light  bulb  
•  walked  down  a  busy  street  and  has  subconsciously  focused  
•  tendency  of  the  eye  to  focus  on  certain  objects  or  people  
•  mid-­‐area  region  of  the  brain  —  called  the  Superior  Colliculus  (SC)  
•  The  human  brain  is  constantly  bombarded  with  informaXon.  It  is  
through  aqenXon  that  it  makes  decisions  efficiently:  it  processes  
relevant  informaXon  and  tunes  out  distracXons  
•  the  SC  is  an  evoluXonary  conserved  midbrain  structure  that  can  be  
found  in  all  vertebrates,  including  fish,  lizards,  birds  and  mammals  
 The  Lancet,  on  June  
19,  1999.    
 
 15%  wider  than  
average  allowing  
beOer  connec'on  
between  its  cells,  
which  could  have  
allowed  them  to  work  
together  more  
efficiently.  

Einstein's  brain  weighed  only  1,230  grams,  which  is  less  than  the  
average  adult  male  brain  (about  1,400  grams).  The  thickness  of  
Einstein's  cerebral  cortex  was  thinner.  However,  the  density  of  
neurons  in  Einstein's  brain  was  greater.    
Einstein  was  able  to  pack  more  neurons  in  a  given  area  of  cortex.  
Effect  of  Drug  abuse  
When  a  person  smokes  drugs,  THC  quickly  passes  from  the  lungs  
into  the  bloodstream.  The  blood  carries  the  chemical  to  the  brain  
and  other  organs  throughout  the  body.  
 
THC  acts  on  specific  brain  cell  receptors  that  ordinarily  react  to  
natural  THC-­‐like  chemicals.  
Drugs  overac'vates  parts  of  the  brain  that  contain  the  highest  
number  of  these  receptors.  effects  include:  
       altered  senses  (for  example,  seeing  brighter  colors)  
       altered  sense  of  'me  
       changes  in  mood  
       impaired  body  movement  
       difficulty  with  thinking  and  problem-­‐solving  
       impaired  memory  
       hallucina'ons  (when  taken  in  high  doses)  
       delusions  (when  taken  in  high  doses)  
       psychosis  (when  taken  in  high  doses)  
Long-­‐Term  Effects  
 
Drugs  also  affects  brain  development.    
 
When  people  begin  using  drugs  as  teenagers,  the  drug  may  impair  
thinking,  memory,  and  learning  func'ons  and  affect  how  the  brain  
builds  connec'ons  between  the  areas  necessary  for  these  func'ons.    
 
Long-­‐term  marijuana  use  has  been  linked  to  mental  illness  such  as:.  
temporary  hallucinaXons  
temporary  paranoia  
worsening  symptoms  in  pa'ents  with  schizophrenia—a  severe  mental  
disorder  with  symptoms  such  as  hallucina'ons,  paranoia,  and  
disorganized  thinking.  
 
Drug  use  has  also  been  linked  to  other  mental  health  problems,  such  as  
depression,  anxiety,  and  suicidal  thoughts  among  teens  
Effect  of  drug  cases  
Biological  Molecular  Machines  
Cells  are  not  built  in  factories  
They  have  to  build  themselves  
A  machine  is  an  apparatus  using  mechanical  power  having  several  parts,  
each  with  a  definite  funcXon  and  together  performing  a  parXcular  task.  
 
A  molecular  machine,  is  “an  assemblage  of  parts  that  transmit  forces,  
moXon,  or  energy  from  one  to  another  in  a  predetermined  manner”.  
 
Ø Living  organisms  are  made  up  of  numerous  biological  machines  which  
are  more  complex  than  arXficially  constructed  machines.  
 
Ø biological  machines  are  necessary  for  performing  life  funcXons.  

Ø Proteins  that  hydrolyze  ATP  perform  mechanical  work  in  the  cells.    

Ø ATP  is  analogous  to  the  fuel  required  by  engines  to  perform  work.  

Ø The  details  of  life  are  finely  calibrated.  

 
Molecular  machines  are  highly  highly  complex  and  we  are  just  beginning  
to  understand  their  inner  workings,  Xll  date  only  a  few  have  been  studied  
sufficiently  by  biologists.    …….  So  we  need  great  engineers  
Main  reason  in  failure  of  our  not  understanding  the  biological  
problems  is  because  the  cells,  proteins,  DNA    are  very  very  Xny,    
Noble  Prize  2017  in  chemistry  
For  discovery  of  Cryo-­‐
Electron  Microscopy  
Jacques   Dubochet   University  
of   Lausanne   in   Switzerland,  
Joachim   Frank   at   Columbia  
University,   and   Richard  
Henderson   at   the   MRC  
United  Kingdom  
The   wavelength   of   electrons  
is   much   shorter   than   that   of  
light,  it  can  reveal  much  finer  
detail  
high-­‐resoluXon,  3D  images  to  
target  cancer  drugs  and  
demysXfy  the  dengue,  
Chikungunya  and  Zika  virus  
and  many  many  more.  
Understanding  complex  phenomena  

Video-­‐3-­‐Biological  clock  
Speciality  of  Our  Inner  Clock  
With  utmost  precision,  our  inner  clock  adapts  our  physiology  to  
the  dramaXcally  different  phases  of  the  day.    
 
The  clock  regulates  criXcal  funcXons  such  as  behavior,  hormone  
levels,  sleep,  body  temperature  and  metabolism.    
 
Our  wellbeing  is  affected  when  there  is  a  temporary  mismatch  
between  our  external  environment  and  this  internal  biological  
clock,  for  example  when  we  travel  across  several  Xme  zones  and  
experience  "jet  lag".    
 
There  are  also  indicaXons  that  chronic  misalignment  between  our  
lifestyle  and  the  rhythm  dictated  by  our  inner  Xmekeeper  is  
associated  with  increased  risk  for  various  diseases.  
 In  18th  century,  Jean  Jacques  
d'Ortous  de  Mairan  studied  
mimosa  plants,  and  found  that  
the  leaves  opened  towards  the  
sun  during  dayXme  and  closed  
at  dusk.    
He  wondered  what  would  
happen  if  the  plant  was  placed  
in  constant  darkness.  He  found  
that  independent  of  daily  
sunlight  the  leaves  conXnued  
to  follow  their  normal  daily  
oscillaXon  (Figure  ).    
 
Plants  seemed  to  have  their  
own  biological  clock.  
  daily  rhythm,  even  
The  leaves  conXnue  to  follow  their  normal  
without  any  fluctuaXons  in  daily  light.  
2017  Nobel  Prize  in  Physiology  or  Medicine  
Jeffrey  C.  Hall,  Michael  Rosbash  and  Michael  W.  Young  
molecular  mechanisms  controlling  the  circadian  rhythm  
Circadian  rhythms  control  when  we’re  at  our  peak  performance  
physically  and  mentally  each  day,  keeping  our  lives  Xcking  in  Xme  
with  Earth’s  day/night  cycle  
living  organisms,  including  humans,  have  an  internal,  
biological  clock  that  helps  them  anXcipate  and  adapt  
to  the  regular  rhythm  of  the  day.  But  how  does  this  
clock  actually  work?  
Using  fruit  flies  as  a  model  organism,  2017  year's  
Nobel  laureates  isolated  a  gene  that  controls  the  
normal  daily  biological  rhythm.    
 
They  showed  that  this  gene  encodes  a  protein  
that  accumulates  in  the  cell  during  the  night,  and  
is  then  degraded  during  the  day.  
 Summary  of  findings  
Ø  circadian  rhythm,  originaXng  from  the  LaXn  words  circa  meaning  
"around"  and  dies  meaning  "day".  

Ø  circadian  rhythms  play  in  coordinaXng  our  lives  with  Earth’s  day,  
controlling  everything  from  your  metabolism  to  the  Xming  of  sleep.    
 
Ø  Young’s  lab  recently  idenXfied  a  prevalent  mutaXon  in  a  human  
clock  gene,  cryptochrome  1,  that  lengthens  the  cellular  clock  and  
makes  it  difficult  to  get  to  bed  before  midnight.  
 
Ø   This  inherited  “night  owl”  gene  is  esXmated  to  be  preqy  common,  
found  in  nearly  1  out  of  75  of  us.    
 
Ø  Those  who  have  a  natural  “night  owl”  tendancy  –  delaying  school  
start  Xmes  by  even  just  one  hour  can  significantly  improve  
academic  performance.  
  Jeffrey  Hall  ,  Michael  Rosbash  and  Michael  Young  discovery  

PER,  the  protein  encoded  by  period,  accumulated  during  the  night  
and  was  degraded  during  the  day.  Thus,  PER  protein  levels  oscillate  
over  a  24-­‐hour  cycle,  in  synchrony  with  the  circadian  rhythm.  

PER  a  protein  having  1224  amino  acids  

They  hypothesized  that  the  PER  protein  blocked  the  acXvity  of  the  
period  gene.    
The  biological  cycle  depends  on  the  rhythmic  formaXon  and  nuclear  
localizaXon  of  the  TIM-­‐PER  complex.    
 
Light  induces  the  degradaXon  of  TIM,  which  promotes  eliminaXon  
 of  PER.    
 
 
 
 
 
 
 
 
 
 
They  reasoned  that  by  an  inhibitory  feedback  loop,  PER  protein  
could  prevent  its  own  synthesis  and  thereby  regulate  its  own  level  in  
a  conXnuous,  cyclic  rhythm.  
 The  Nobel  Prize  in  Physiology  or  Medicine  2019    

The  Nobel  Prize  in  Physiology  or  Medicine  2019  was  awarded  jointly  to  William  G.  
Kaelin  Jr,  Sir  Peter  J.  Ratcliffe  and  Gregg  L.  Semenza  "for  their  discoveries  of  how  
cells  sense  and  adapt  to  oxygen  availability.”  
 
For  their  ground-­‐breaking  discovery  of  the  HIF-­‐1  (hypoxia-­‐inducible  factor  1)  
protein,  which  controls  genes  in  response  to  changes  in  oxygen  availability.  The  
finding  has  implicaXons  in  understanding  and  treaXng  low-­‐oxygen  health  
condiXons  such  as  blood  disorders,  blinding  eye  diseases,  cancer,  diabetes,  
coronary  artery  disease  etc.    
  An  example  of  Molecular  machine:  Hemoglobin  
 
• Hemoglobin  is  found  in  the  Red  blood  cells.  

• Hemoglobin  in  the  blood  carries  oxygen  from  the  respiratory  organs  
(lungs  or  gills)  to  the  rest  of  the  body  (i.e.  the  Xssues).    

• Hemoglobin  is  the  protein  that  makes  blood  red.    

• It  is  composed  of  four  protein  chains,  two  alpha  chains  and  two  beta  
chains,  each  with  a  ring-­‐like  heme  group  containing  an  iron  atom.    

• Oxygen  binds  reversibly  to  these  iron  atoms  and  is  transported  
through  blood.  
   
• “Hemoglobin  is  a  remarkable  molecular  machine  that  uses  moXon  
and  small  structural  changes  to  regulate  its  acXon.”    
•  Hemoglobin  structure  has  been  explained  by  Max  Perutz’s  18-­‐
year  quest.    

•  Hemoglobin  uses  iron  within  its  protein  structure  to  carry  

oxygen  from  the  lungs  to  the  rest  of  the  body  through  the  
blood.  
 
•  The  breathing  required  a  protein  channel  to  open  for  O2  to  
access  the  heme.  

•  The  coupled  change  of  local  and  quaternary  conformaXons  

between  oxy  and  deoxy  forms  explained  the  cooperaXvity  of  O2  
binding.  

Video-­‐3-­‐Oxygen  transport  
•  Some  organisms  like  snails  and  crabs,  on  the  other  hand,  use  
copper  to  transport  oxygen,  so  they  truly  have  blue  blood.  
 
•  Aside  from  oxygen  transport,  hemoglobin  can  bind  and  transport  
other  molecules  like  nitric  oxide  and  carbon  monoxide.  

•   Nitric  oxide  affects  the  walls  of  blood  vessels,  causing  them  to  
relax.  This  in  turn  reduces  the  blood  pressure.    
 
•  Carbon  monoxide,  is  a  toxic  gas.  It  readily  replaces  oxygen  at  the  
heme  groups,  forming  stable  complexes  that  are  difficult  to  
remove.    

•  This  abuse  of  the  heme  groups  blocks  normal  oxygen  binding  and  
transport,  suffocaXng  the  surrounding  cells.    
 Sickle-Cell Disease: A Simple Change in
Primary Structure
10 µm 10 µm

Red blood Normal cells are Red blood Fibers of abnormal

cell shape full of individual cell shape hemoglobin deform
hemoglobin cell into sickle
molecules, each shape.
carrying oxygen.

A slight change in primary structure can affect a

protein’s conformation and ability to function.

Sickle-cell disease, an inherited blood disorder, results

from a single amino acid substitution in the protein
hemoglobin, unable to transport oxygen
Video-­‐4-­‐sickle  cell  anemia  video  
Secondary
Primary Quaternary Red Blood Cell
and Tertiary Function
Structure Structure Shape
Structures
Normal Molecules do not
1 hemoglobin associate with one
2 another; each carries
3 oxygen.
Normal

4
α
5 β subunit β
6
7 α
5 µm
β

Exposed hydro- Sickle-cell Molecules crystallized

1 phobic region hemoglobin into a fiber; capacity to
carry oxygen is reduced.
2
3
Sickle-cell

4
α
5 β
6 β subunit
7 α
β 5 µm

hOp://www.rcsb.org/pdb/educa'on_discussion/molecule_of_the_month/images/hb-­‐anima'on.gif  
ArXficial  Blood  
•  Blood  transfusions  have  saved  countless  lives.    
•  However,  the  need  for  matching  blood  type,  the  short  life  of  stored  
blood,  and  the  possibility  of  contamina'on  are  s'll  major  concerns.    
•  The   main   challenge   is   keeping   the   four   protein   chains   of  
hemoglobin  together,  the  four  chains  rapidly  fall  apart.    
•  To   avoid   this   problem,   novel   hemoglobin   molecules   have   been  
designed   where   two   of   the   four   chains   are   physically   linked  
together.  two  addiXonal  glycine  residues  form  a  link  between  two  
of  the  chains,  prevenXng  their  separaXon  in  soluXon.    
•  There   are   two   basic   approaches   to   construcXng   an   oxygen  
therapeuXc.   The   first   is   perfluorocarbons   (PFC),   chemical  
compounds  which  can  carry  and  release  oxygen.    
•  The  second  is  haemoglobin  derived  from  animals,  or  arXficially  via  
recombinant   technology,   or   via   stem   cell   producXon   of  
red  blood  cells  in  vitro.  
 The  Nobel  Prize  in  Physiology  or  
Medicine  2016  Yoshinori  Ohsumi  
AminopepXdase  1  and  Autophagy  
 
Cells  are  constantly  changing,  building  new  
molecules  when  needed  and  breaking  down  
others  when  they  are  finished  with  them.    
 
PDB  entry  5jh9  
The  proteasome  and  exosome  systems  recycle  
biomolecules  one  at  a  Xme,  but  the  cell  also  has  
a  system  for  bulk  recycling,  termed  autophagy.    
The  name  means  “self-­‐eaXng,”  and  that’s  just  
what  the  cell  does.    
 
It  packages  up  the  waste  and  delivers  it  to  its  
internal  digesXve  system,  lysosomes,  where  
everything  is  broken  down  by  a  soup  of   PDB  entry  4r8f.  
digesXve  enzymes.  
 Rotary  Motors  
ATP  synthase  
•  Dephosphoryla'on  of  adenosine  triphosphate  (ATP)  
provides  energy  for  many  biochemical  reac'ons.  
•     
•  ATP  is  primarily  produced  by  the  enzyme  ATP  
Synthase    

•  (ADP  +  Pi  -­‐-­‐-­‐>  ATP).    

•  Energy  currency  of  biological  systems  

“Rastogi,  V.  K.  &  Girvin,  M.  E.  Structural  changes  linked  to  proton  transloca'on  by  subunit  c  of  
the  ATP  synthase.Nature  402,  263–268  (1999)”.  
ATP  synthase  :  Molecular  turbines  

•  hOp://www.youtube.com/watch?v=KU-­‐B7G6anqw  
•  FuncXon  similar  to    turbines  of  hydroelectric  water  plant  

•  Use  of  kineXc  energy  of  water  flowing  through  the  dam  

•  Proton  Gradient  like  water  of  the  dam  

•  Protons  flow  from  higher  to  lower  gradient  

•  Synthase  components  rotate  in  response  to  proton  flow  

•  Generated  RotaXonal  energy  coupled  to  ATP  synthesis      

 Video-­‐5-­‐ATP-­‐
synthase  

hqp://www.callutheran.edu/BioDev/omm/jmol/atp_synthase/atp_synthase.html